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21

Saline / Fluid Therapy and its Applications

« Last post by LamiyaJannat on May 31, 2021, 11:35:18 AM »

Fluid therapy is one of the most common therapies provided in small animal medicine. Patients are given fluids for many reasons, and the number of available fluids is growing. Knowing why fluids are ordered, the goals and limitations of fluid therapy, and how fluids are chosen is a key competency for veterinary technicians. This article reviews some of the reasons fluid therapy may be ordered for a patient, how to administer and monitor fluid therapy, and the fluid types available in the United States.

Body Water Compartments

To understand fluid therapy and its applications, one must first understand the distribution of fluid and water in the body. Total body water (TBW) comprises approximately 60% of a patient’s body weight.1 Approximately 67% of TBW is found inside the body’s cells and is referred to as intracellular fluid (ICF). The remaining 33% of TBW is the extracellular fluid (ECF), which is further divided as follows:

•   Interstitial fluid, which bathes cells and tissues (~24% of TBW)
•   Plasma, the liquid portion of blood, which constitutes most of intravascular volume (~8%–10% of TBW)
•   Transcellular fluid, which comprises synovial joint fluid, cerebrospinal fluid, bile, and the fluid in the linings of the peritoneal cavity, pericardium, and pleural space (~2% of TBW)

A helpful rule of thumb to simplify the distribution of fluids in the body is the 60:40:20 rule: 60% of a patient’s body weight is water, 40% of body weight is ICF, and 20% of body weight is ECF.1

The body is considered a closed system, meaning that any fluid lost must come from one of the compartments listed above. In the case of hemorrhage, for example, fluid is lost from the intravascular space (i.e., plasma) but also from the ICF in the cells lost (e.g., red blood cells, white blood cells). In addition to losses, fluid can and does move between compartments in a dynamic and ever-changing fashion. When providing fluid support to patients, technicians must keep in mind which compartment needs to be replenished or what derangement needs to be corrected. This knowledge helps guide both fluid choice and the method used to administer fluid therapy.

Reasons for Fluid Therapy

Veterinary professionals provide fluid therapy to patients for many reasons, including correction of dehydration, expansion and support of intravascular volume, correction of electrolyte disturbances, and encouragement of appropriate redistribution of fluids that may be in the wrong compartment (e.g., peritoneal effusion).²

BOX 1 Clinical Signs of Shock

•   Vasoconstriction
o   Pale mucous membranes
o   Prolonged capillary refill time
o   Peripheral temperature < core temperature
o   Reduced urine output
•   Decreased mentation
•   Tachycardia (cats may present with bradycardia)
•   Hypotension (poor pulse quality)
•   Reduced oxygen saturation (low SpO2)
•   Lactate >2 mmol/L
•   Metabolic acidosis

The first step in determining whether a patient needs fluid therapy is a full physical examination, including collection of a complete history. The veterinary staff must assess whether the patient is perfusing its tissues well, check for dehydration, and evaluate losses from any of the fluid compartments.³

Inadequate Perfusion

Patients that cannot adequately perfuse their tissues require immediate intervention with fluid therapy to restore perfusion and correct shock. Shock is defined as the critical imbalance between the delivery of oxygen and nutrients (carried by blood) to tissues and the tissues’ demand for these components. If allowed to persist, this imbalance can lead to acute decompensation and death. Restoring perfusion and, subsequently, oxygen and nutrient delivery to tissues is crucial to survival in these patients.1

Shock is a life-threatening emergency and must be recognized and treated immediately on presentation. Patients may present with several clinical signs (BOX 1), and owners may report a history of recent fluid loss, such as intractable vomiting, severe diarrhea, or hemorrhage. Once shock is recognized, access to the intravascular compartment must be achieved and fluid resuscitation initiated as soon as possible (see Ways to Provide Fluid Therapy), with the goal of restoring intravascular volume and flow, thus improving perfusion and delivery of oxygen and nutrients to starving tissues.

Oxygen delivery to the tissues (DO2) depends on cardiac output and arterial oxygen content. Cardiac output is the product of stroke volume and heart rate. Stroke volume is defined as the amount of blood ejected from the left ventricle during systole and is a product of preload (the amount of blood entering the heart), afterload (the amount of resistance in the vasculature to the flow of blood from the heart), and contractility (the heart’s ability to contract). Once perfusion and, by extension, DO2 is restored, homeostasis can be reestablished and the shock state will be remedied. Correction of perfusion deficits is demonstrated by normalization of the forward perfusion parameters, listed in BOX 2.1

BOX 2 Forward Perfusion Parameters

•   Heart rate
•   Pulse quality
•   Respiratory rate
•   Mucous membrane color
•   Capillary refill time
•   Mentation
•   Temperature and color of digits

Dehydration

Loss of fluid from the intracellular and interstitial compartments leads to dehydration. If severe, dehydration can be detected in derangements in forward perfusion parameters1 as well as by the tests listed below. Any patient determined to be more than 10% dehydrated is considered severely dehydrated4 and requires immediate fluid resuscitation and careful monitoring.5 Dehydration must not be confused with hypovolemia: dehydration describes a water deficit in the interstitial and intracellular compartments, whereas hypovolemia describes a loss of fluid in the intravascular space.4

Hydration status can be assessed using several simple tests. One of the easiest to perform is a skin tent test to check the turgor, or moisture level, of the skin. To perform this test, the skin over the thorax or lumbar region is pulled away from the back. In a well-hydrated animal, the skin immediately returns to its normal resting position. If the tent formed remains standing, it can be an indication of dehydration.1,5 When performing this test, veterinary technicians can often appreciate a “tacky” or “sticky” feeling in the underlying tissue, which is further evidence of dehydration. The skin tent test can be confounded by both emaciation (decreased turgor even if euhydrated) and obesity (increased turgor in the face of dehydration) and must be considered in relation to other parameters and physical examination findings. Age is another factor to consider: loss of skin turgor progresses with increasing age, and neonates exhibit very little skin tenting even when dehydrated.
Another way to check for dehydration is to feel for moistness on the mucous membranes. This is most easily accomplished by sliding a finger along a patient’s gum line or inside the cheeks. If the membranes themselves are dry or sticky, it may indicate dehydration. In the case of vomiting animals, it is necessary to differentiate excess saliva in the mouth from mucous membrane moisture.

In patients with normal kidney function, oliguria can indicate dehydration, and the small amount of urine produced will likely be concentrated (urine specific gravity [USG] >1.030).5 Other laboratory parameters that change with dehydration include packed cell volume and total protein (PCV/TP) levels, which demonstrate hemoconcentration (high PCV) and hyperproteinemia (high TP) in dehydrated patients5 due to the loss of the fluid portion of the blood as the body tries to maintain fluid balance and homeostasis. Serial measurements of both USG and PCV/TP can help the veterinary care team evaluate the effectiveness of fluid resuscitation efforts, as both levels should decrease as intravascular volume is restored and the interstitial fluid and ICF compartments are replenished.

Previous, Ongoing, and Anticipated Losses

Consideration of fluid losses is an important part of determining a fluid therapy plan. These losses may have occurred before presentation to the clinic—such as animals with a history of protracted vomiting or diarrhea—or may be anticipated after treatment has been instituted, as is often seen in cases of postobstructive diuresis in cats with urinary obstruction. These losses must be factored in when deciding the type, amount, and route of fluid therapy. When calculating fluid losses, veterinary technicians should include urination, defecation/diarrhea, vomiting, removal of effusions or gastric contents, fluid loss from drains, and insensible losses (such as from panting).

Ways to Provide Fluid Therapy

Even veterinary technicians who have been in practice for only a short while have likely seen fluids given several ways. Oral, subcutaneous, intravenous, intraosseous, and even intraperitoneal routes are all used, depending on the species receiving fluid therapy and why it is needed.

Oral Route

By far the simplest mode of fluid therapy, providing water per os can correct some conditions, including mild salt toxicity and mild cases of dehydration. Providing water via the oral route is as simple as offering the patient a bowl with a premeasured volume of water on a set schedule and measuring the amount consumed. However, in patients that have gastrointestinal pathology (i.e., parvovirus infection) or are unable to consume adequate amounts of water to maintain normal urine production or to establish and maintain fluid homeostasis, other means of fluid resuscitation must be used.

Subcutaneous Route

Subcutaneous fluids are a mainstay of veterinary therapy. Subcutaneous fluid administration is used for many disease conditions, including cases of mild vomiting and diarrhea or mild dehydration, or to support kidney function in animals with chronic kidney disease. It is relatively simple to provide fluids via the subcutaneous route, and many owners can be trained to provide this therapy at home, mitigating the need for hospitalization. As with other therapies given subcutaneously, it takes time for subcutaneous fluids to be absorbed into the bloodstream; thus the subcutaneous route is not appropriate to treat life-threatening conditions such as severe dehydration or shock.

Intravenous Route

IV fluid therapy is very common in veterinary practice and allows practitioners to restore intravascular volume, correct dehydration, and administer IV medications. IV catheter placement is a core nursing competency for veterinary technicians and allows for IV fluid therapy in emergency presentations and hospitalized patients alike. In addition, access to the vascular space allows for other therapies, including transfusions, medications, and parenteral nutrition.

In emergency situations or when a large volume of fluid is needed over a short amount of time, selecting a catheter with a large bore and a short length is preferable to allow for rapid infusion of fluids. This is a function of Poiseuille’s law, which governs the flow of fluid through a tube: essentially, the shorter the tube, the smoother the flow, and the larger the tube’s diameter, the faster the flow, meaning that large-bore, short catheters are the best choice when a large volume of fluid must be delivered quickly, such as in cases of hypovolemic shock.6,7 T-ports and additional tubing (e.g., extension sets) may decrease both the amount of fluid and the speed of delivery. In an emergency situation, it is best to minimize any extra IV accessories that might impede flow.

In addition to peripheral access, IV fluid therapy can be delivered through central line catheters. These catheters are longer than typical peripheral IV catheters and reach the central circulation via the vena cava. Central lines are commonly placed in the jugular vein, with the tip of the catheter sitting just outside the entrance to the right atrium to facilitate measurement of central venous pressures, if desired. Jugular central line catheters can be placed with a guidewire (i.e., Seldinger technique) or a peel-away introducer. They are available with multiple lumens to enable sampling, concurrent administration of incompatible fluids, and administration of hypertonic solutions that may cause phlebitis if given peripherally (e.g., dextrose concentrations >7.5%). The central circulation can also be reached with a long, through-the-needle catheter (e.g., Intracath) placed in either the lateral saphenous vein or the medial femoral vein or a peripherally inserted central catheter (PICC) in the same vessels. Because of their long length, smaller bore, and longer time usually required for placement, central catheters are not recommended for emergency fluid therapy, but can be maintained for long periods, making them well-suited to longer-term fluid therapy.

Intravenous Intraosseous Route

Intraosseus (IO) catheters are an excellent choice for providing drugs and fluids to patients in which IV access is difficult—if not impossible—to obtain in a timely fashion. Patients with severe hypotension or complete cardiovascular collapse (i.e., patients in cardiac arrest), that are severely dehydrated, or in which IV access is not obtainable (as in patients with edema, burns, thrombosis, or obesity) can benefit from placement of a catheter in the medullary cavity of a bone (IO). This route is also very useful in tiny patients, such as neonates and pocket pets (e.g., hamsters, gerbils). The materials are readily available in most, if not all, veterinary practices, and placement may mean the difference between life and death. The IO route is fast and has been proven8,9 to provide access to the central circulation comparable to the access provided by central venous catheterization, making it the first choice for administration of drugs and fluids when IV access cannot be achieved.
For all of the advantages of the IO route, there are several limitations. Fluid cannot be provided at a rate equivalent to that of IV access, and the needles are not designed for long-term use. Most sources1,2,4,7,10 recommend removal of IO access devices within 72 to 96 hours of placement to avoid the development of osteomyelitis or bone infections, as long as IV access can be obtained.

Monitoring

Veterinary technicians are responsible for providing therapies in as safe a manner as possible; this includes fluid therapy. Safety can be maintained with vigilant monitoring. To monitor a patient’s perfusion status, technicians should observe forward perfusion parameters (BOX 2). Normalization of these parameters is a good indication that fluid therapy is being provided successfully. In the laboratory, technicians can perform serial measurements of PCV/TP and USG. In patients that presented in a state of dehydration with increased PCV/TP, lowering of these values indicates a return to normal fluid levels in the intravascular space and an improvement in overall hydration. Increasingly dilute urine means that the patient’s kidneys have detected an increase in intravascular volume and a restoration of overall fluid balance.

One of the easiest and most sensitive ways to monitor fluid therapy in patients is with multiple weight checks throughout the course of therapy. Since TBW is 60% of a patient’s body weight, increases in any fluid compartment leads to a commensurate increase in the patient’s overall weight. However, an increase >10% from baseline admission weight should prompt an investigation of the possibility that the patient is becoming overhydrated, also known as becoming fluid overloaded.
Swelling of the conjunctiva without signs of inflammation or irritation is known as chemosis. This is a late sign of fluid overload; it is incumbent on veterinary technicians to recognize earlier signs such as increased respiratory rate and effort, increased breath sounds (e.g., crackles), or clear nasal discharge.

Fluid overload is a major complication of fluid therapy and can lead to pulmonary edema, ascites, and peripheral edema with the potential for development of compartment syndrome. A patient who becomes tachypneic, develops clear nasal discharge, or is found to have crackles on thoracic auscultation while receiving fluid therapy should be suspected of becoming overhydrated. If these signs are noted, particularly in combination with an increase in body weight, IV fluid therapy should be stopped and the veterinarian should be notified immediately.11 Chemosis (swelling of the conjunctiva) is a late sign of fluid overload and requires urgent treatment including cessation of IV fluids and potential administration of diuretic agents.

Fluid Types Available

Several types of fluids are available, ranging from crystalloids to synthetic colloids to natural colloids (i.e., blood products). Each type has its place in the treatment of various conditions and pathologies found in veterinary patients. It is easiest to differentiate fluids based on their purpose: maintenance or replacement therapy. The components of common maintenance and replacement fluids available to veterinary practitioners in the United States. The resources listed in the Recommended Reading box can provide more detailed explanations of fluid types and their effects.

Patients presented as an emergency often require immediate intravascular expansion in the form of crystalloid boluses, or large volumes of crystalloid fluids. Crystalloid fluids move quickly from the intravascular space into other fluid compartments, primarily the intracellular compartment. Less than one-third of the crystalloid volume administered intravenously persists in the vasculature 1 hour after administration,4 making these fluids an excellent choice for treating dehydration and electrolyte derangements and correcting free water deficits.

Crystalloid fluids can be categorized as follows:

•   Free water: 5% dextrose in sterile water or 0.45% saline. This hypotonic (i.e., containing fewer solutes than ICF) solution replenishes the interstitial fluid and ICF compartments.

•   Replacement solutions: These balanced, isotonic solutions are designed to replenish the ECF compartments, including increasing intravascular volume and restoring perfusion. Isotonic fluids contain a solute concentration that approximates that of ICF, and crystalloids that are considered “replacement” fluids have compositions that closely match the electrolyte balance and pH of ECF,1 making them ideal to replace losses from that fluid compartment (e.g., dehydration).

•   Maintenance solutions: These balanced, isotonic solutions have less sodium and more potassium than replacement fluids and may be more suitable for long-term fluid therapy after restoration of intravascular volume and correction of electrolyte derangements. Maintenance fluids are rarely used alone—they are usually combined with a ratio of 0.9% sodium chloride1 (aka “normal” or “isotonic” saline) to more closely match the composition of the fluid in the intravascular space, preventing unwanted fluid shifts between compartments.

•   Hypertonic solutions: 7% to 23.4% saline. These fluids contain a solute concentration higher than that of ICF and rapidly expand intravascular volume by drawing water from the interstitial and intracellular compartments. Because of this oncotic pull, hypertonic solutions should never be used in cases of severe dehydration.

Colloids

Many practitioners also use colloids (either synthetic or natural) in an emergency to expand the intravascular compartment without the risk of fluid overload posed by infusing large volumes of crystalloid fluids. Colloids contain large, osmotically active particles that work to hold fluid in the vasculature after administration.

Synthetic colloids are fluids with large molecules designed to provide oncotic pressure support within the intravascular space. Natural colloids are blood products such as whole blood, packed red blood cells (pRBCs), plasma, and albumin. Whole blood and pRBCs have the added benefit of providing oxygen-carrying capacity, helping to prevent and treat hypoxia.
The use of colloids is highly controversial in human medicine and becoming so in veterinary medicine as well,12 with recent research13 implicating a link between the use of a synthetic colloid and the development of acute kidney injury in dogs.

Developing and Implementing a Fluid Therapy Plan

There is a helpful guideline when it comes to fluid therapy: Replace like with like. This means if a patient has lost blood, that fluid should be replaced with plasma, pRBCs, or whole blood. If a patient has lost body fluids through diarrhea, vomiting, or excessive urination, replacement should be with similarly constituted isotonic crystalloid fluids. While development of the fluid plan is ultimately the veterinarian’s purview, it is important for veterinary nurses and technicians to understand the fluids available and for what conditions they might be used in clinical practice.

Fluid therapy in the veterinary hospital or clinic has 3 primary phases, which can overlap and alternate, depending on how a patient presents and the progression of its disease process. The resuscitation phase refers to correcting shock and other life-threatening fluid deficits; the replacement phase is the time taken to replace dehydration deficits; and the maintenance phase covers fluids provided during hospitalization to support and maintain homeostasis. BOX 3 provides examples of fluid choices in some specific disease processes.

BOX 3 Appropriate Fluid Choices for Selected Disease Processes

•   Cardiac disease: Low-dose maintenance crystalloid, such as 0.45% saline with dextrose (may require potassium and or magnesium supplementation)

•   Vomiting/diarrhea: Replacement crystalloid, such as lactated Ringer’s solution, Normosol-R, or
Plasmalyte-A

•   Diabetic ketoacidosis: Replacement crystalloid, such as lactated Ringer’s solution, Normosol-R,
Plasmalyte-A

•   Hemorrhage: Natural colloid, such as plasma, whole blood, pRBCs

The amount of fluid to be provided to a patient must be calculated carefully, taking into account the need for intravascular volume expansion, the profundity of perfusion deficits, the degree of dehydration, and the severity of electrolyte derangements, among other considerations. BOX 4 lists common fluid therapy calculation formulas.

BOX 4 Fluid Therapy Formulas

Calculation of Dehydration Deficit1
Body weight (kg) × % dehydration as a decimal = liters of fluid required to correct dehydration
Calculation of Maintenance Fluid Requirements*
Dogs: Body weight (kg)0.75 × 132 = 24-hour fluid requirement in milliliters
Cats: Body weight (kg)0.75 × 80 = 24-hour fluid requirement in milliliters
Ongoing losses (e.g., from diarrhea, vomiting, or polyuria) must be calculated and added to the total maintenance requirement obtained from these formulas.
*UC Davis School of Veterinary Medicine fluid therapy formula.
 

Source: todaysveterinarynurse

22

Eggshell Remover / Calcium and Phosphorus Deficiency in Poultry

« Last post by LamiyaJannat on May 31, 2021, 11:18:25 AM »

Both calcium and phosphorus are required for the synthesis of bone. These elements also play an important role in the nervous system, blood clotting and muscle contraction. Stored in bone they provide not only mechanical strength but also a reserve for periods of increased requirement (e.g., during egg laying) or periods of nutritional deficiency.

Calcium and phosphorus deficiencies can lead to abnormal skeletal development, or rickets in the growing chick, and osteoporosis in older birds. Although rickets is frequently associated with a deficiency of calcium, the condition is most likely to arise in situations of vitamin D deficiency (Wise, 1979). Osteoporosis results from calcium being removed from bone to meet other needs, and this causes porous and brittle bones (Long et al., 1984).

Newly hatched chicks need an immediate supply of dietary calcium for bone development. Since at this age chicks are osteoporotic, an absence of calcium or vitamin D makes this condition more pronounced.

The medullary cavity is the central area inside a bone where bone marrow is stored. Red bloods cells, white blood cells and fat calls are formed in the bone marrow and it has a vascular section which supplied the bone with nutrients and transports the cells around the body.

The first signs of a deficiency of calcium, phosphorus or vitamin D, or all of these, are:

•   Lameness
•   Stiff legs
•   Ruffled feathers
•   A reduction in growth
•   Leg bones appear rubbery
•   Joints become enlarged
•   A calcium deficient diet may cause paralysis followed by death

In growing pullets, a calcium deficiency can result in increased general activity and environmental pecking (Hughes and Wood-Gush, 1973). The pullet’s requirement for calcium is relatively low during the growing period, but the bird still needs properly balanced phosphorous and calcium in its diet. When laying starts the need is increased at least four times, largely for the production of eggshells (Jacob et al., 2003) as the egg shell is composed primarily of calcium carbonate. Thus an early sign of calcium deficiency in laying hens is the production of thin and soft-shelled eggs.

Calcium is stored in the medullary cavity of the bone capable of rapid calcium turnover (See diagram). Whereas caged hens may suffer calcium depletion and brittle bones, birds on the ground tend not to suffer as they recycle calcium and phosphorus through coprophagy (Jacob et al., 2003).

The nutritional role of phosphorus is closely related to that of calcium. The ratio of dietary calcium to phosphorus affects the absorption of both these elements. An excess of either can interfere this process and cause production losses.
Low dietary phosphorus during lay can lead to elevated incidence of cage layer fatigue, reduced bone ash, increased severity of osteoporosis, and diminished bone strength (Webster, 2004).

In addition to its function in bone, phosphorus also plays a key role in carbohydrate metabolism, fat metabolism, and the regulation of the acid-base balance of the body (Jacob et al., 2003).

Control and Prevention of Calcium and Phosphorus Deficiency

Encouraging birds to do more exercise as in free ranging systems will improve bone strength and minimize the risk of osteoporosis.

Generally, the calcium content of poultry feeds of plant origin is low. Prevention of deficiency requires the adequate dietary provision of calcium, but young birds should not be fed a high calcium layer diet as an excess of dietary calcium can tie up phosphorus making it unavailable, and may result in rickets. The balance between calcium and phosphorous is key. Excess calcium in the growing period can also result in kidney damage, visceral gout, calcium deposits in the ureter and mortality.
If all feed for the birds is bought in, the feed mill will balance calcium and phosphorous in the ration. Farmers who mill and mix their own feed should be particularly careful to avoid causing deficiencies. There is a difference in requirement for calcium between laying hens and broilers with laying hens having a higher need for calcium of around 4g per day – equivalent to the weight of an average eggshell. Soluble limestone grit or oyster shell grit may be used to provide a source of calcium for laying hens (Reid and Weber, 1976). Calcium may also be provided in the form of mixed grit. Mixed grit contains soluble grit composed of limestone, oyster shell and other mollusc shells, and insoluble grit in the form of granite and flint. Particle size affects calcium availability with larger particles being retained for longer in the upper digestive tract and calcium being released more slowly. Oyster shell for example provides a slow release of calcium. This may be important for the continuity of shell formation (Jacob et al., 2003).

Dolomitic limestone should not be fed to poultry as it contains at least 10% magnesium, and can interfere with calcium absorption creating a deficiency, as opposed to alleviating it.

Breeding may be an effective way of combating osteoporosis. Some genetic lines may be more prone to osteoporosis than others (Bell and Siller, 1962 cited by (Webster, 2004)). A study was conducted which looked at the genetic heritability of bone index and strength in five generations of while leg horn end-of-lay hens. Some bone strength traits were been shown to be moderately to strongly heritable (Bishop et al., 2000).

Phosphorus in plant material is only partly available to the chicken, and for periods of the bird’s development can become unavailable. For this reason, poultry feeds need supplementation with phosphorus (Hopkins et al., 1987). Microbial phytases can be used in reduced-P layer diets containing feeds with high levels of P bound up in the form of phytate e.g. rice bran (Tangendjaja et al., 2002).

An interaction between particle size and phosphorus concentration occurs when chicks are fed diets deficient in phosphorus. For example, whilst food efficiency increases with fine and pelleted corn diets, calcium and phytate phosphorus retention are greatest with coarse corn diets (Kilburn and Edwards, 2001).

Treating Calcium and Phosphorus Imbalances

Provided irreversible damage has not been done to bone structure, altering the calcium content of the diet should be effective. Expert nutritional advice should be sought regarding therapeutic inputs of calcium to deficient birds. Damaged bone structure may be improved by encouraging exercise, provided the diet has been improved.
A calcium boost using water-soluble sources can help get the diet back into balance. Providing ad lib oyster shell will then allow hens to take what they need for maintenance.

Source: FARM HEALTH ONLINE

23

Antiseptic / Antiseptics and Disinfectants

« Last post by LamiyaJannat on May 31, 2021, 11:08:02 AM »

Cleansers, antiseptics, and disinfectants play critical roles in preventing infectious disease transmission in veterinary medicine. From use as a presurgical scrub to disinfection after an outbreak, these products are relied upon by veterinarians for safe and effective germicidal activity. The beneficial effects of cleansing or disinfecting practices have been known for many years; the efficacy of hand washing was demonstrated as early as the 1840s by Ignaz Semmelweis, a Hungarian obstetrician. Following Pasteur’s identification of infective agents as the cause of disease, Joseph Lister suggested the use of antiseptics in the field of surgery. His treatment of the hands with 1 : 20 carbolic lotion and his initiation of methods for chemical sterilization of bandages, dressings, and surgical instruments and for antisepsis of wounds began aseptic surgery.

Cleansers, antiseptics, and disinfectants are differentiated by their intended use and characteristic properties, not by their chemical content. A cleanser aids in physical removal of foreign material and is not necessarily a germicide. An antiseptic is a biocide applied to living tissue, whereas a disinfectant is a biocide applied to inanimate objects. Because certain antiseptics may be inactivated on inanimate surfaces and because certain disinfectants are hazardous to living tissue, the two should not be used interchangeably; however, these products may still have a very similar chemical content. Even products with the identical active chemical moiety may be formulated in such a way (e.g., exposure time, concentration) as to prevent their interchangeable use. Products formulated as disinfectants (and sanitizers or sterilants) to be used on inanimate surfaces, objects, or instruments are regulated by the Environmental Protection Agency (EPA). Antiseptics for use on living tissue must be registered with the Food and Drug Administration (FDA), along with some chemicals used on critical and semicritical devices.

Different cleaning, antiseptic, and disinfectant protocols exists for many different clinics, farms, procedures, and uses in veterinary medicine; no one compound is applicable, appropriate, or effective for every use.

Cleansers

Cleansers contain surfactants or detergents that remove dirt and contaminating organisms by solubilization and physical means. Cleansers are often a critical step to proper disinfection or antisepsis as removing gross contamination from an area prior to disinfection or antisepsis treatment maximizes their efficacy. Depending on the application and use, cleansing may be sufficient.

Cleansers can be classified into three types based on the presence and charge of the hydrophilic portion of the molecule: anionic, cationic, and nonionic. Soaps are anionic surfactants of the general structure R-COO−Na+. Dissociation in water to R-COO− liberates a molecule with both a hydrophilic and a hydrophobic portion, which can emulsify and solubilize hydrophobic dirt, fat, and protoplasmic membranes. Once solubilized, this contamination can be rinsed away with water. The ability to solubilize membranes renders soaps antibacterial against gram-positive and acid-fast bacteria. The anionic nature of soaps, however, causes them to be inactivated in the presence of certain positive ions such as free Ca+ in hard water and in the presence of cationic detergents. The mixture of soaps and quaternary ammonium compounds forms a precipitate, which terminates the activity of both compounds. Inclusion of antiseptic compounds in soap preparations has given them a wider antibacterial spectrum.

The quaternary ammonium compounds (QACs) are examples of cationic surfactants with germicidal activity. These compounds have been widely used as disinfectants (see Section Examples of disinfectant use in Veterinary Medicine). Cationic surfactants combine readily with proteins, fats, and phosphates and are thus of limited value in the presence of serum, blood, and other tissue debris (Huber, 1988). In addition, use with materials such as gauze pads and cotton balls makes them less germicidal owing to absorption of the active ingredients.

Antiseptics

An antiseptic is a chemical agent that reduces the microbial population on skin and other living tissues. Because in most cases its mechanism of action involves nonspecific disruption of cellular membranes or enzymes, caution must be taken not to harm host tissue. An ideal antiseptic would have a broad spectrum of activity, low toxicity, high penetrability, would maintain activity in the presence of pus and necrotic tissue, and would cause little skin irritation or interference with the normal healing process.
The use of antiseptics has been suggested in situations which require maximal reduction of bacterial contamination (Larson, 1987) such as when defense mechanisms are compromised after surgery, during catheterization or insertion of other invasive implants, and in immunocompromised states due to immune defects, cytotoxic drug therapy, extreme old or young age, or extensive skin damage (burns and wounds).

Disinfectants

Disinfection is a process that eliminates most, if not all, pathogenic organisms, excluding spore forms, from an inanimate object. Disinfection is sometimes incorrectly confused with sterilization, a process that completely eliminates all microbial forms by a physical or chemical means. True chemical sterilization necessitates the use of an EPA-registered agent capable of killing all infective organisms, including fungal and bacterial spores, usually within 10 hours. Sometimes, however, chemical sterilants can be considered disinfectants when shorter exposure periods are used. The treatment of objects that are too large to soak in disinfectant, such as cabinets, exam tables, chairs, lights, and cages, is considered surface disinfection. Immersion disinfection is the immersion of smaller objects in disinfectant for sufficient time to kill the majority of contaminating, pathogenic organisms.

The ideal characteristics of a disinfectant includes a broad spectrum, fast action, activity in the presence of organic material (including blood, sputum, and feces), compatibility with detergents, low toxicity, low cost, ease of use, and residual surface activity. They should not corrode instruments or metallic surfaces or disintegrate rubber, plastic, or other materials, and should be odorless and economical (Molinari et al., 1982).

The ability to kill different classes of microorganisms further categorizes disinfectants into high, intermediate and low levels. High-level disinfection destroys all microorganisms except high concentrations of bacterial spores. Intermediate-level disinfection inactivates acid-fast microorganisms, including Mycobacterium tuberculosis, most viruses and fungi, but not necessarily bacterial spores. Low-level disinfection kills most bacteria, some viruses, and some fungi, but not tubercle bacilli or bacterial spores. In addition, low-level disinfection usually occurs in less than 10 minutes.

A second classification system is intended to divide instruments and patient-care items into three categories based on risk of infection involved in their use (Spaulding, 1968). In this system, items are classified as: (i) critical – those that enter or penetrate skin or mucous membranes (e.g., needles, scalpels), usually at a sterile site; (ii) semicritical – those that touch intact mucous membranes (e.g., anesthesia equipment, endoscopes); and (iii) noncritical – those that do not touch mucous membranes but may contact intact skin (e.g., stethoscopes, cages, tables, food bowls). In general, items classified as critical should be sterilized, semicritical items require high-level disinfection, and noncritical items require low to intermediate-level disinfection.

Popular Antiseptic and Disinfecting Agents

Alcohol
Alcohols are one of the most popular antiseptic and disinfecting products, used every day in veterinary clinics and laboratories. Although many alcohols are germicidal, the two most commonly used as disinfecting agents are ethyl and isopropyl alcohol. These compounds are both lipid solvents and protein denaturants. They kill organisms by solubilizing the lipid cell membrane and by denaturing membrane cellular proteins. Alcohols are most effective when diluted with water to a final concentration of 70% ethyl or 50% isopropyl alcohol by weight. It is thought that at greater concentrations, initial dehydration of cellular proteins makes them resistant to the denaturing effect (Molinari and Runnel, 1991). Alcohols have excellent antibacterial activity against most vegetative gram-positive, gram-negative, and tubercle bacillus organisms but do not inactivate bacterial spores. They are active against many fungi and viruses, principally enveloped viruses due to alcohol’s lipid-solubilizing action.
The alcohols are not recommended for high-level disinfection or chemical sterilization due to their inactivity against bacterial spores and reduced efficacy in the presence of protein or other bioburden. Blood proteins are denatured by alcohol and will adhere to instruments being disinfected. Fatal Clostridium spp. infections have occurred postoperatively that were the result of contaminated surgical instruments that had been disinfected with alcohol containing bacterial spores (Nye and Mallory, 1923). After repeated and prolonged use, alcohols can damage the shellac mounting of lensed instruments, can swell or harden rubber and certain plastic tubing (Rutala, 1990), and can be corrosive to metal surfaces. Alcohols are flammable; thus caution must be taken in their storage and when used prior to electrocautery or laser surgery. In deciding between ethyl and isopropyl alcohol, it is important to consider isopropyl’s inactivity against hydrophilic viruses, its less corrosive nature, and the abuse potential for ethyl alcohol (grain alcohol).

Both isopropyl and ethyl alcohol are also commonly used, effective antiseptics, with only subtle differences in their action. Because their effectiveness is drastically reduced by organic matter such as feces, mucus, and blood, they are most effective on “clean” skin. They produce rapid reduction in bacterial counts (Lowbury et al., 1974), with contact times of 1–3 minutes, resulting in elimination of almost 80% of organisms. Rapid evaporation limits contact time; however, residual decreases in bacterial counts are seen to occur after the alcohol has evaporated from the skin. Although alcohols are among the safest antiseptics, toxic reactions have been reported in children. Alcohol can be drying to the skin and can cause local irritation. In efforts to minimize this drying effect, emollients such as glycerine have been added with good results (Larson et al., 1986).

Halogens

Iodine and chlorine both demonstrate antimicrobial activity and are used as antiseptics or disinfectants. Elemental iodine has germicidal activity against gram-positive and gram-negative bacteria, bacterial spores, fungi, and most viruses. It exerts these lethal effects by diffusing into the cell and interfering with metabolic reactions and by disrupting protein and nucleic acid structure and synthesis. Iodine has a characteristic odor and is corrosive to metals. It is insoluble in water and thus is prepared in alcohol (tincture) or with solubilizing surfactants (“tamed” iodines). Tincture of iodine, used as early as 1839 in the French Civil War, is most effectively formulated as a 1–2% iodine solution in 70% ethyl alcohol. In this form, most (approximately 90%) bacteria are killed within 3 minutes of application. The antibacterial activity of this combination is greater than that of the alcohol alone. Tincture of iodine, however, is irritating and allergenic, corrodes metals, and stains skin and clothing. It is also painful when applied to open wounds and is harmful to host tissue; therefore, it can delay healing and increase the chance of infection. For these reasons, this preparation has fallen out of favor as an antiseptic or disinfectant. Strong tinctures of iodine have been used as blistering agents in the equine industry.

Efforts to reduce the undesirable aspects of tinctures while retaining the powerful killing action of iodine have led to the introduction of tamed iodines known as iodophors. In this preparation, iodine is solubilized by surfactants, which allow it to remain in a dissociable form. Application of this product allows for slow continual release of free iodine to exert its germicidal effects. The iodophors have a similar spectrum of activity to aqueous solution; are less irritating, allergenic, corrosive, and staining; and have prolonged activity after application (4–6 hours). Common solubilizing carriers include polyvinylpyrrolidone (called PVP-iodine or povidone-iodine, PI) as well as other nonionic surfactants, making iodophors excellent cleansing agents as well as antiseptics and disinfectants. Iodophor solutions retain their activity in the presence of organic matter at pH <4 (Huber, 1988). The water-soluble carriers have been postulated to interact with epithelial surfaces to increase tissue permeability, thereby enhancing iodine’s killing efficacy.

Proper dilution to 1% iodine is necessary for maximum killing effect and minimal toxicity. More-concentrated solutions are actually less efficacious, presumably due to stronger complexation preventing free iodine release. It takes approximately 2 minutes of contact time for release of free iodine (Lavelle et al., 1975). Literature reports indicate that iodophors are quickly bactericidal, virucidal, and mycobactericidal but may require prolonged contact times to kill certain fungi and bacterial spores. Iodophors formulated as antiseptics are not suitable as hard-surface disinfectants, due to insufficient concentrations of iodine.
Consideration must be taken of iodine’s ability to be systemically absorbed through the skin and mucous membranes. The extent of absorption is related to the concentration used, frequency of application, and status of renal function (the principal excretory route) (Swaim and Lee, 1987). Complications of iodophor absorption include increased serum enzyme levels, renal failure, metabolic acidosis (Pretsch and Meakins, 1976), and increased serum free iodide. If renal function is normal, serum iodine concentrations quickly return to normal. Clinical hyperthyroidism and thyroid hyperplasia have been reported after treatment with PI (Scheider et al., 1976; Altemeier, 1976).

Chlorine-containing solutions were first introduced by Dakin in the early 1900s in the chemical form of sodium hypochlorite. They are effective bactericidal, fungicidal, virucidal, and protozoacidal agents. The chemical forms most commonly used today include the hypochlorites (sodium and calcium) and organic chlorides (chloramine-T). In either form, the germicidal activity is due to release of free chlorine and formation of hypochlorous acid (HOCl) from water. The mechanisms of action of these compounds include inhibition of cellular enzymatic reactions, protein denaturation, and inactivation of nucleic acids (Dychdala, 1983). Dissociation of HOCl to the less microbicidal hypochlorite ion (OCl−) increases as pH increases, and thus the solution may be rendered ineffective above pH 8.0 (Weber, 1950). Mixing NaOCl with acid liberates toxic chlorine gas, and NaOCl decomposes when exposed to light.

Low concentrations of free chlorine are active against M. tuberculosis (50 ppm) and vegetative bacteria (<1 ppm) within seconds. Concentrations of 100 ppm destroy fungi in less than 1 hour, and many viruses are inactivated in 10 minutes at 200 ppm. Household bleach is 5.25% (52,500 ppm); thus dilutions of 1 : 100 to 1 : 250 should result in effective germicidal concentrations although more-concentrated solutions are often recommended (1 : 10 to 1 : 100).

The use of the hypochlorites as disinfectants are limited by several characteristics. Chlorine solutions are corrosive to metals and destroy many fabrics. Because chlorine solutions are unstable to light, they must be prepared fresh daily. Hypochlorites are inactivated by the presence of blood more so than are the organic chlorides (Bloomfield and Miller, 1989). They have a strong odor and are not suitable for enclosed spaces. In addition, hypochlorites may lead to irritation of mucous membranes and may form toxic bioproducts when interacting with other chemicals. Despite these shortcomings, chlorine solutions are commonly used as low-level disinfectants on dairy equipment, animal housing quarters, hospital floors, and other noncritical items. Of 12 disinfectant solutions evaluated for their ability to kill the dermatophyte Microsporum canis, those containing hypochlorite were most effective. Also found effective were benzalkonium chloride and glutaraldehyde-based products; phenolics and anionic detergents were considered inadequate (Rycroft and McLay, 1991). The hypochlorites are not recommended for routine use as antiseptics because they are very irritating to skin and other tissues and they delay healing. There is, however, research to suggest diluted household bleach can be applied to control superficial pyoderma in dogs.
Several compounds from a class called N-halamines (oxazolidinones or imidazolidinones) have been developed, which are water-soluble solids that have been shown to be bactericidal, fungicidal, virucidal, and protozoacidal in water disinfection at low total halogen concentrations (1–10 mg/l). They are noncorrosive and tasteless and odorless in water. They are extremely stable in water even in the presence of organic loads. Their potential use in poultry processing to control Salmonella has been evaluated (Smith et al., 1990).

Biguanides

Chlorhexidine (Chx) is popular synthetic cationic antiseptic compound (1-1′-hexamethylenebis[5-(p-chlorophenyl)biguanide]) with better activity against gram-positive than against gram-negative organisms. The compound lacks sporicidal activity. Chlorhexidine kills bacteria by disrupting the cell membrane and precipitating cell contents. It has also been suggested that membrane-bound adenosine triphosphatases, specifically inhibition of the F1 ATPase, may be a primary target for Chx (Gale et al., 1981). It is active against fungi, fairly active against M. tuberculosis, but poorly active against viruses. The antibacterial activity of Chx is not as rapid as that of the alcohols; however, as a 0.1% aqueous solution, significant killing action is evident after only 15 seconds. Additionally, Chx solutions have the longest residual activity, remaining chemically active for 5–6 hours and retaining their activity in the presence of blood and other organic material. Being cationic, it is inactivated by hard water, nonionic surfactants, inorganic anions, and soaps. Dilution with saline causes precipitation and its activity is pH dependent. It has extremely low toxicity even when used on intact skin of newborns (O’Neill et al., 1982). Chlorhexidine is available in a detergent base as a 4% solution or as a 2% liquid foam. Traditionally, it has widely been used as a presurgical antiseptic, wound flush, and teat dip. Formulations of chlorhexidine and alcohol have also been described and appear to improve efficacy. Its use as a disinfectant are not well described.

Polyhexamethylene biguanide (PHMB) is a polymeric biguanide with activity against gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus equi. PHMB rapidly kills bacteria by disrupting the cytoplasmic membrane resulting in leakage and precipitation of cellular contents (Broxton et al., 1983). PHMB has been used to treat infections in the eye, mouth, and vagina and has been formulated in contact lens disinfectants and mouth rinses. It was shown to be nontoxic as a component of an ear flush for dogs (Mills et al., 2005) and when impregnated in a gauze wound dressing, reduced growth of underlying gram-positive and gram-negative bacteria in vitro (Lee et al., 2004).

Aldehydes

Two related aldehyde disinfectants are formaldehyde and glutaraldehyde (GLT). Formaldehyde has antimicrobial activity both as a gas and in liquid form. Formalin, the aqueous form, is 37% formaldehyde by weight. It inactivates microorganisms by alkylating the amino and sulfhydryl groups of proteins and ring nitrogen atoms of purine bases (Favero, 1983). Formaldehyde is an effective but slow bactericide, virucide, and fungicide, requiring 6–12 hours contact time. It is effective against M. tuberculosis, bacterial spores, and most animal viruses, including foot-and-mouth disease virus. Its action is not affected by organic matter and it is relatively noncorrosive to metals, paint, and fabric. Formaldehyde alone is considered a high-level disinfectant and in combination with alcohol can be used as a chemical sterilant for surgical instruments. However, due to irritating fumes and pungent odor at low concentrations (approximately 1 ppm), and because the National Institute for Occupational Safety and Health requires it to be handled as a potential carcinogen, thereby limiting worker exposure time, formaldehyde’s use as a disinfectant has been limited.

Glutaraldehyde, a saturated dialdehyde, is similar to formaldehyde but without some of its shortcomings. It has better bactericidal, virucidal, and sporicidal activity than formaldehyde. Its biocidal activity is related to its ability to alkylate sulfhydryl, hydroxyl, carboxyl, and amino groups affecting RNA, DNA, and protein synthesis (Scott and Gorman, 1983). Acidic GLT solutions are not sporicidal; thus, they must be “activated” by alkalinizing agents to a pH between 7.5 and 8.5. Once activated, these solutions have a limited shelf life (14 days) due to polymerization of the GLT molecules (Rutala, 1990). Newer formulations (stabilized alkaline GLT, potentiated acid GLT, GLT-phenate) have increased shelf life (28–30 days) and excellent germicidal activity (Pepper, 1980). GLT has gained wide acceptance in high-level disinfection and chemical sterilization due to several favorable properties, including wide spectrum of activity. Low surface tension allows GLT to penetrate blood and exudate without coagulating proteins. It retains its biocidal activity in the presence of organic matter. It is noncorrosive to metal, rubber, and plastic and does not damage lensed instruments. GLT solutions must be used in well-ventilated areas, since air concentrations of 0.2 ppm are irritating to the eyes and nasal passages (CDC, 1987). Contact times of less than 2 minutes for vegetative bacteria, 10 minutes for fungi, and 3 hours for bacterial spores were necessary using a 2% aqueous alkaline GLT solution (Stonehill et al., 1963). Activity against the tubercle bacillus was found to be somewhat variable; at least 20 minutes at room temperature is needed to reliably kill these organisms with 2% GLT. When used as a high-level disinfectant, a minimum of 1% GLT should be used. GLT-phenate formulations should be used with caution since they were shown to be less effective than other aldehyde solutions in decreasing bacterial counts from some medical instruments (Ayliffe et al., 1986). GLT disinfectants were found to more effectively reduce duck hepatitis B virus infectivity when they contained additives such as alcohol, an ammonium chloride derivative, and a surfactant (Murray et al., 1991). The caustic nature of both formaldehyde and GLT makes them inappropriate as antiseptics, and in fact, protective gloves should be worn when using the aldehyde disinfectants.

Gluteraldehyde and QAC combinations have been formulated (e.g., Synergize™, Preserve International, Reno, NV) and largely marketed as a cleaner and disinfectant for use in animal (e.g., swine and poultry) production facilities.

Oxidizing Compounds

Conflicting reports concerning hydrogen peroxide’s efficacy as a germicide make evaluating its utility in disinfection and antisepsis difficult. Although it has been reported to have bactericidal (Schaeffer et al., 1980), virucidal (Mentel and Schmidt, 1973), and fungicidal (Turner, 1983) activity, the activity of hydrogen peroxide is nonpenetrable and short lived. For this reason hydrogen peroxide antiseptic use is most valuable in the initial treatment of recently contaminated wounds. Because 3% hydrogen peroxide has been shown to be damaging to tissues, including fibroblasts (Lineweaver et al., 1982), it is not considered suitable for routine wound care. It is, however, considered a stable and effective disinfectant and is used in the disinfection of soft contact lenses. More recently, accelerated hydrogen peroxide products have been formulated to also contain a surfactant and stabilizer, which improve antimicrobial activity. These products are being implemented in many veterinary clinic settings for use as a disinfectant.

Other oxidizing agents include potassium peroxymonosulfate (PPMS), an oxidizing agent used in disinfection systems of pools and hot tubs. More recently, it has been formulated with potassium chloride and organic acids and salts (i.e., sulphamic acid, malic acid, sodium hexametaphosphate, and sodium dodecyl benzene sulphonate) resulting in a disinfectant effective against over 580 infectious agents including viruses, gram-positive and gram-negative bacteria, fungi (molds and yeasts), and mycoplasma (EPA Master Label). It is marketed as a powder because it is stable in solution for approximately 1 week. It is not inactivated by organic challenge and has been found to be user friendly to both humans and animals. It is widely used as a high-level disinfectant for surfaces in laboratories, dental care facilities, and hospitals; for decontaminating laundry; for air disinfection; and in food processing and transport. Use of peracetic acid, sodium perborate, benzyl peroxide, and potassium permanganate have also been reported in human and veterinary literature.

Phenols

Carbolic acid, a phenol, is the oldest example of an antiseptic compound. However, due to severe toxicity, it is no longer appropriate for use as an antiseptic. These agents act as cytoplasmic poisons by penetrating and disrupting microbial cell walls. Most commercially available phenolic products contain two or more compounds that act synergistically, resulting in a wider spectrum of activity, including against M. tuberculosis. Sodium o-phenylphenol is effective against staphylococci, pseudomonads, mycobacteria, fungi, and lipophilic viruses, and against ascarids, strongyles, and tichurids. Cresols are substituted phenols and are more bactericidal and less toxic and caustic than phenols. Phenolics are not recommended for disinfection of anything other than noncritical items, because of residual disinfectant on porous materials causing tissue irritation even when the items have been thoroughly rinsed, because of strong odors, and because of absorption into feed.

Triclosan (Irgasan DP 300; 2,4,4′ trichloro-2′-hydroxydiphenyl ether) is a chlorinated diphenyl ether or bisphenol that possesses high antibacterial activity particularly against many gram-positive (e.g., Bacillus subtilis, Mycobacterium smegmatis, Staphylococcus aureus) and gram-negative bacteria (Escherichia coli, Salmonella enterica serotype Typhimurium, Shigella flexneri

Source: veteriankey

24

Acidifier / Types of Acidifier

« Last post by LamiyaJannat on May 31, 2021, 10:59:58 AM »

Acidifier ensures the growth of the animal and reduces the increase of pathogenic bacteria in the gastrointestinal region. The major purpose of using this acidifier is to improve growth performance and better the profitability in poultry production. Organic acids have multi usages in poultry feeds as they help in preservation to control microbial growth, reduction of the feed buffer capacity, inhibition of pathogenic bacteria and betterment of nutrient digestibility.

It is important that poultry birds keep a low gastric pH, so they can activate enzymes which are critical for protein digestion. This low pH also curbs pathogens. Pathogenic microbes compete with the birds for vital nutrients in feed and grow quickly which higher pH leading to harm in health and productivity of the birds. By the use of Acidifier make feed and digestive system grow and multiply pathogenic organisms, which increases the productivity immensely.

Advantages

•   Less corrosive
•   Completely bio-degradable
•   Less stringent smell of acids
•   No resistance
•   User-friendly
•   No withdrawal times

Activity in Feed

•   It creates acidic conditions in feed which controls the growth and multiplication of harmful pathogens.
•   Improves the appetizing of feed and which helps in improving feed intake.
•   Lower downs the acid binding capacity of feed.

Activity in Bird

Effects on Pathogenic Flora

•   Acidifies all parts of the digestive region
•   Results in low intestinal pH, which reduces the pathogens like Salmonella, clostridium perfingers, Listeria and Compylo-bacter jejuni.
•   Acidification favors growth of acidophilus bacterial flora that prevents multiplication of pathogens.

Effects on Nutrient Digestion

•   Improves the digestion, absorption and utilization of feed
•   Cut downs the number of microbes that results in thinning of intestinal wall and increased size of villi which improves the absorption and utilization of nutrients
•   Stimulates the activation of digestive enzymes

Dry Acidifier Powder Composition

Dry constitutes unique property blend of buffered organic acids and their salts for use in poultry feed.

Dosage

For Low risk feed   1-1.5 Kg/Ton
For High risk feed   1.5-2.5 Kg/Ton

Dry Plus (Concentrated Acidifier Powder) Composition

Dry Plus Acidifier contains a unique proprietary blend of concentrated direct acting buffered organic acids and their salts for use in Poultry Feed.

Dosage

For Low-risk feed   0.75-1 Kg/Ton
For High-risk feed   1-1.5 Kg/Ton

Liquid (Acidifier Liquid) Composition

Liquid contains a combination of direct acting organic acids and pH regulators for use in poultry feed.

Dosage

Breeders   1000-1500 ml/ Ton of feed
Broilers   500-1000 ml/ Ton of feed
Layers   300-500 ml/ Ton of feed

WA (Water Acidifier Liquid) Composition

•   Formic Acid
•   Lactic Acid
•   Citric Acid
•   Acetic Acid
•   Phosphoric Acid
•   Organic Copper
•   Bioflavonoids
•   Polyphenols

Usage

For drinking water: Broiler, Breeder, Layer 0.2 ml per Litre of water (Usage depends on water pH)

Source: Vetline

25

Opportunities in Pharmaceuticals / Top most Business Opportunities in Pharmaceutical/Ayurvedic Sector

« Last post by LamiyaJannat on May 28, 2021, 01:31:30 AM »

Pharmaceutical Business is one of most profitable business throughout world. Main problem that is faced by most of person are from where to start, not matter whether they are from pharma background or from any other background. Here we are going to prepare a list of businesses that you can start in pharmaceuticals sector. Only marketing company or manufacturing company is not a single option in pharmaceutical sector. You have number of business opportunities available. Click at option name to read in detail about mention opportunity.

1. Pharmaceutical Marketing/Trading Company:

Most profitable and easy to start if you have sales and marketing experience but don’t worry if you don’t have. You can also start after developing few qualities in you. How many types you can sell your products in marketing companies are:

    Branded/Ethical Marketing
    Generic Marketing
    Pcd/Franchise Distribution ship
    OTC marketing
    Institutional Sales
    Export

2. Pharmaceutical Manufacturing Company:

Pharmaceutical manufacturing is base of all pharmaceutical marketing companies. It requires some what more formalities and documentations to start manufacturing company but it is also one of the best option to make profit and establish pharma business. You can sell your manufactured products as per below marketing types:

    Marketing type mentioned for marketing/trading company
    Third Party/Contract Manufacturing
    Loan License Manufacturing

Manufacturing types you can choose from:

    Any of all Pharmaceuticals products and formulations sections
    Pharmaceutical Raw material manufacturing
    Surgical and Dressing
    Veterinary pharma products
    Disposal Syringes
    Transdermal Pouches
    Softgel Capsule plant
    Ayurvedic manufacturing Unit

3. Carrying and Forwarding Agents (C&F):

Carrying and Forwarding agents are those who receive products from company godown and after repacking, they distribute it to stockists or distributors. They get their fixed percentage margin. Every type of marketing, there is need of CnF. CnF could be appointed at area, state, region basis depend at sale of company.

4. Wholesaler/Stockist/Distributors:

Pharmaceutical products distribution is also good way to start own pharma business. Wholesaling/Distribution is good margin able and profitable business. There are different types of distributors present:

    Branded Products Distributors
    Generic Products Distributors
    Pcd/Franchise Distributors
    OTC/Institution Sales Distributors

5. Retail/Chemist/Pharmacy:

Opening a chemist shop could be one of the best option for doing pharma business. It needs less investment and more margin as compare to above mentioned pharma businesses. You have to consider only location of chemist shop. Retailers/Pharmacies/Chemists are placed at ground level in pharma distribution chain. One has to make sure about availability of all running products. Online pharmacy concept is also getting popularity day by day. It could be leading business opportunities in coming future in pharmaceutical sector as use of internet & online sale is increasing.

6. Pharma PCD/Franchise Marketing:

For marketing and sales professionals in pharmaceutical sector, pcd pharma franchise is one of the best suitable work with minimum investment and maximum profit. If some one has good hold in market and number of doctors in his circle who can prescribe his products, then pcd franchise marketing is best option. You can associates with any Pharma or Ayurvedic Pcd Franchise Company for starting pharma business with low investment. Main advantages are:

    Minimum investment as it can be started with less than ten thousand.
    Easy availability of pcd/franchise companies
    Number of options in company selection and product list selection
    Highly profitable etc

7. Pharmaceutical Raw Material Supplier:

As number of pharma manufacturer is increasing, there is also increasing the demand of Raw material suppliers. Most of pharma raw material suppliers in India is trading or marketing nature. They depend at import or few big raw material manufacturers for procurement of raw material. Big pharma companies deal directly with manufacturers for raw material procurement or involve in direct importing of raw material whereas small manufacturers have less demand and can’t indulge in getting direct supply from manufacturer or importer. They are dependent at Raw material suppliers. It could be great of option for pharmaceutical business to start with.

8. Food and Dietary Supplement (Nutraceutical) Marketing Company:

Food and Dietary supplements has huge demand in healthcare and pharma sector. Most commonly used dietary supplements are protein powders, vitamins like B-complex/D/D3/A/E/C, minerals like iron supplements/calcium supplements, lycopene preparations, DHA, Methylcobalamine preparations etc. Every doctor’s prescription has one or more food and dietary supplements in it. Due to high demand, it could be highly profitable business. One can market these products for Human purpose or Veterinary purpose or both. Veterinary supplements has also huge demand. One has to register under FSSAI to start marketing of Nutraceuticals.

9. Food and Dietary Supplement (Nutraceutical) Manufacturing Company:

Due to less regulation and easy to start, we recommend start with food and dietary supplements manufacturing company if you want to enter into manufacturing sector. As we have discussed, there is huge demand and every pharma company has a large portion of its product list as food & dietary supplements products. One can get number of third party or contract manufacturing orders or start own marketing of food and dietary supplements. One has to take license of manufacturing from FSSAI to manufacture Nutraceuticals.

10. Cosmetic Manufacturing Company:

Cosmetic and Beauty products manufacturing is also popular among pharmaceutical professionals. For starting manufacturing of cosmetic products, one need diploma in pharmacy or equivalent education and should be registered under state pharmacy council. Or you can appoint person with above qualification. It requires less investment and less requirements to start cosmetic and beauty products manufacturing company.

11. Consultancy and Legal Firms:

You don’t know about manufacturing and marketing/sales. You also don’t want to go into distribution channel. But you have experience of administration, regularity affairs and setting up plants, launching of new company divisions, brands, export etc. You can start your consultancy firms to provide all documentation and services support to new pharma set-ups or existing pharma set-ups. Even persons having sale, marketing or manufacturing experience can provide consultancy to specific firms on basis of their experience in sales, brand promotion, formulation developments etc. and help them grow & get paid for your knowledge and experience.

12. Pharma Printing Material Production:

It may be out of matter but it is most demand able business type in present time. In pharma production, procurement of printing material takes most of time. Every company faces delay in printing material problem. Every pharma printing material supplier has more work as compare to its capacity. It requires less documentation and formalities and it is margin able too. Main printing material supplied to pharma companies are:

    Box
    Label
    Foil
    Catch covers
    Visual aids
    Promotional inputs e.g. leaf lets, reminders, pads etc.

13. Pharmaceutical Machinery Business (Manufacturing/Marketing):

With growth of pharmaceutical sector and increase in pharmaceutical units, there is huge demand of machinery that are used in manufacturing plant. There may be three way of supplying machinery to units:

    Own Manufacturing Units of Machinery and its parts
    Trading/Marketing of Machinery
    Import/Export of Pharmaceutical Machinery

Main machinery used in pharmaceutical units Tablet punching rotary, capsule filling machine, blister, grinder, mixers, liquid filling machine, cap sealers, alu-alu machine, analytic instruments etc.

14. Pharmaceutical Blogging and News Website:

Blogging is one of the business that could be started without any investment and infrastructure. You can start blogging or website related to pharma, ayurvedic, health, pharmacy etc. Only one condition is required, you should have good knowledge of subjects, you are writing for. Write good content. After six months of blogging, you can apply for Google adsense. Adsense is google advertising business. If Google approves your account. You can show google ads at your blog. Google pays at PPC (Pay Per Clict) Basis. Provide information to your user & Readers and google will start to show your blog page at good rank. Many SEO agencies will tell you many lies about how to take your blog page at google first page but google hasn’t disclose its way for search to any one.

Source: pharmafranchisehelp

26

QC Lab / Digitization, automation, and online testing: The future of pharma quality contr

« Last post by LamiyaJannat on May 27, 2021, 08:17:25 PM »

Emerging technologies can make quality control (QC) faster and more efficient. What do pharma companies need to do to become QC leaders?

The emerging technologies that characterize Industry 4.0—from connectivity to advanced analytics, robotics and automation—have the potential to revolutionize every element of pharma-manufacturing labs within the next five to ten years. The first real-life use cases have delivered 30 to 40 percent increases in productivity within already mature and efficient lab environments, and a full range of improvements could lead to reductions of more than 50 percent in overall quality-control costs. Digitization and automation will also ensure better quality and compliance by reducing manual errors and variability, as well as allowing faster and effective resolution of problems. Use cases have demonstrated more than 65 percent reduction in deviations and over 90 percent faster closure times. Prevention of major compliance issues can in itself be worth millions in cost savings. Furthermore, improved agility and shorter testing time can reduce QC-lab lead times by 60 to 70 percent and eventually lead to real-time releases.

While most of the advanced technologies already exist today, few pharmaceutical companies have seen any significant benefits yet. On one side, quality leaders often struggle to define a clear business case for the technological changes, which makes it difficult for them to convince senior management that lab digitization or automation can deliver significant impact. On the other side, companies rarely develop a clear long-term lab-evolution strategy and blueprint, which can lead to some costly investments with unclear benefits. For example, many companies have already taken steps to become paperless by first simplifying paper records to minimize the number of entries and then digitizing lab testing records. Now those moves are being superseded by new advances in equipment connectivity that enable direct transcription of thousands of data points without any manual data transcription and without any reviews.

To capture opportunities offered by existing and emerging technological advances, companies should set clear goals, define robust business cases for any level of investment, and engage in rapid piloting of the new technologies followed by fast scale-up of pilots that deliver promising results. To succeed in the future, pharma companies need both the foresight to make long-term strategic investments, including those in R&D for developing and filing new test methods, and the agility to adapt those plans as technologies rapidly evolve.

Multiple digital and automation technologies have created opportunities for change in pharmaceutical laboratories. Most pharma labs have not yet achieved digital transformation, but labs can aim for one of the three future horizons of technological evolution (Exhibit 1).

Exhibit 1
As pharmaceutical labs incorporate new technologies, they will evolve to become more digitized, automated, and distributed in nature.
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Digitally enabled labs achieve at least 80 percent paperless operations. These labs transition from manual data transcription and second-person verification to automatic data transcription between equipment and the general laboratory information-management system (GLIMS).

Digitally enabled labs use advanced real-time data analytics and ongoing process verification to track trends, prevent deviations or out-of-specifications, and optimize scheduling. They employ digital tools like smart glasses to translate standard operating procedures into step-by-step visual guidance on how execute a process. They create a digital twin of a lab to predict impacts before making physical changes. All these are currently available technologies, with time to impact as short as three months for each case.

An average chemical QC lab can reduce costs by 25 to 45 percent by reaching the digitally enabled lab horizon. Potential savings at an average microbiology lab would be in the 15 to 35 percent range. Productivity improvements come from two main sources:

    the elimination of up to 80 percent of manual documentation work
    the automation, and especially optimization, of planning and scheduling to improve personnel, equipment, and materials utilization

With fewer manual errors and data-enabled analyses of root causes, labs can reduce investigation workloads by as much as 90 percent.

Digitally enabled labs also reap compliance-improvement benefits from reduced errors and variability, as well as seamless data retrieval and analysis. The increased productivity and scheduling agility can also reduce lab lead time 1 by 10 to 20 percent.

One large global pharma company transitioned to a digitally enabled lab within its Italian digital lighthouse plant. Lab productivity at the site jumped by more than 30 percent after the company implemented advanced schedule optimization by harnessing a modular and scalable digital-twin platform adapted to the lab-specific scheduling constraints. The site also used advanced analytics to reduce deviations by 80 percent, eliminating reoccurring deviations altogether and accelerating deviation closure by 90 percent.

Pharma companies have many options when it comes to choosing and customizing technological solutions to create digitally enabled labs. In addition to custom digital-twin and advanced-analytics platforms, other solutions include real-time insights from IoT platforms such as ThingWorx, lab scheduling software such as Bookitlab or Smart-QC, and digital assistants with visual operating procedures from providers such as Tulip.
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Automated labs use robots, cobots, or more specific advanced automation technologies to perform all repeatable tasks like sample delivery and preparation. At the automated-lab stage, some high-volume testing (for example, microbial detection and water for sterility) is performed online instead of in physical labs. Automated labs can also use predictive-maintenance technologies to plan for infrequent tasks, such as for large-equipment maintenance, which can be performed by lab analysts with remote expert support.

While full implementation of digital enablement is not a prerequisite, automated labs can build upon digitization to deliver greater value and higher cost savings. Automated microlabs can enable additional cost reduction of 10 to 25 percent inside the lab, while also capturing a similar amount of savings outside the lab. The same improvements at chemical labs have the potential to produce 10 to 20 percent savings beyond that achieved by digitally enabled labs. The productivity improvements come from automation of up to 80 percent of sample-taking and sample-delivery tasks and of up to 50 percent of sample-preparation tasks, as well as from the reduction of equipment-maintenance cost through remote monitoring and failure prevention. Automation also reduces sampling and related logistics tasks performed by operations outside the lab, which produces the equivalent of up to 25 percent lab-cost savings 2 for microlabs and up to 8 percent equivalent lab-cost savings for chemical labs.

Pharmaceutical companies can also achieve additional benefits beyond efficiency. Remote-monitoring and predictive-maintenance capabilities built into the equipment will decrease downtime and ultimately enable companies to reduce their use of expensive devices, such as chromatography, near-infrared spectrometers, and isolators. By shifting to instantaneous microbial detection for environmental monitoring, companies may also reduce their overall lab lead time by 40 to 75 percent.

Technologies already exist—in healthcare and research labs or in manufacturing operations—that can be adapted to pharma-manufacturing labs in a relatively straightforward way to reach the automated-lab horizon. Vendors offering solutions include Aethon and MICROMO (sample distribution systems), BioVigilant, Colifast (online microbial-testing systems), Metrohm and Sotax (automated sample prep), Milliflex, Light Guide Systems (work-flow optimization with visual guidance), and Scope (assisted maintenance).

Distributed quality control represents a true disruption to traditional ways of providing quality control. At these sites, nearly all routine product testing would take place on the production line, enabling real-time release testing (RTRT). Equipment and robots at distributed QC facilities have artificial-intelligence capabilities. In the distributed QC scenario, labs continue to perform specialty and stability testing. This testing can take place off-site in a centralized location. Adoption of process analytical technology (PAT) and RTRT has been relatively slow because of regulatory filing and approval requirements. To be able to make a smooth shift to online testing in the future, operations need to start collaborating with R&D now to develop an optimal quality-control and filing strategy, especially for new products and manufacturing sites.

Distributed QC facilities primarily add value by significantly reducing the footprint and costs of a traditional lab. Because of significant R&D-investment requirements, as well as the need for equipment and operational changes, existing sites with stable or declining volumes are unlikely to make a compelling business case for distributed QC in the short and even medium term. At the same time, sites that have been rapidly growing or under construction may be able to capture significant value from reducing capital-expenditure investment for building or expanding traditional QC labs if they can move a significant share of routine testing online. Distributed QC and real-time release would also enable true continuous-manufacturing processes (Exhibit 2).

Exhibit 2
Digitization and automation will transform quality-control work in the lab and on the shop floor by introducing new ways of working.
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For example, Biogen plans to use this distributed QC method of real-time release and review by exception in its new manufacturing facility near Solothurn, Switzerland. When production starts up in 2019, the Solothurn facility will achieve raw-material control through screening and genealogy, with minimal testing using rapid identification and electronic data exchange. Bioreactor processes controlled through in-line instruments will eliminate the need for process control sampling. The new facility will have adaptive process control levers, lab execution by recipe, and automated data transcription from all equipment, all based on a deep understanding of raw materials, processes, and product characteristics. The integrated control system allows employees to see data and react in real time. 3
Sidebar
On the path to the future: How one company is exploring and adopting new quality-control technologies

As pharma companies start exploring ways to build distributed QC facilities, they may be able to pull in relevant technologies from adjacent spaces. For example, the PharmaMV platform from Perceptive Engineering and the Sipat platform from Siemens could provide the advanced process control necessary to enable parametric release. Meanwhile, AI systems from companies such as Arago and IBM could allow pharma companies to automate tasks that historically have been performed by highly trained expert employees. (For a view on one company’s efforts, see sidebar, “On the path to the future: How one company is exploring and adopting new quality-control technologies.”)
Typical implementation pitfalls hampering successful transformation and value capture

As pharma labs evolve, they face significant costs associated with implementing IT and automation solutions. Even expensive solutions can deliver a strong positive return on investment (ROI), but many companies, unfortunately, struggle to capture value from these digital upgrades. These companies typically encounter one or more of the following pitfalls:

Not having a clear vision of what evolution horizon is the right target for a specific lab. While most labs can make a solid business case for the digitally enabled horizon, not all labs have sufficient volumes and operational setup to justify automation and distributed QC. For example, it could be hard to justify an investment in automating a smaller lab where the potential cost savings might be less than $200,000 a year, whereas the same investment could quickly generate positive ROI for a large sterile facility with significant environmental-monitoring volumes.

Not having a compelling business case for the transformation. Many companies start implementation of costly IT systems without a clear understanding of the full benefits such solutions can generate. This often results in delays in implementation and the rollout of partial solutions. For instance, labs might move to paperless systems on individual modules but still need significant manual efforts to move data from one system to another. This can lead to situations where analysts must record test results into a paper log before manually entering the data into a laboratory information-management system (LIMS). This manual-entry step prevents them from capturing the full savings they should get from automating documentation.

   
Targeting a fully tested end-to-end future-state prototype rather than testing and rapidly scaling up high-value solutions to capture quick wins. For example, schedule automation and optimization can be implemented quickly and start generating significant value even if a lab is not yet mostly paperless and fully digitized.

Lacking proper planning or management for rollout of new systems and technologies. In extreme cases, it can take pharma companies several years and more than $100 million to implement a LIMS. Given such a lengthy time frame and the fast pace of technological change, some of the LIMS capabilities are liable to become obsolete before they get rolled out across the entire network. Pharma companies need skilled resources to accelerate the rollout and should avoid the temptation to engage in excessive customization at each site. A poor rollout can cost five to ten times more and take three to five times longer than a properly planned investment executed with good long-term planning.

Not having a full understanding of the capabilities of the systems they acquire. Pharma companies may purchase a system such as LIMS to comply with data-integrity regulations without truly understanding or considering the system’s potential to generate improvements in productivity.

Pursuing automation rather than optimization. Scheduling automation can deliver 2 to 3 percent of the QC cost savings, but automation plus dynamic scheduling optimization can yield three to four times more value.

Self-imposed constraints from a perceived need to validate all systems and technologies. Many of the high-impact changes, such as optimized scheduling and data-enabled deviation analysis, do not require validation and refiling.

Missing the skill set to extract full value from their data. Most typical pharma labs do not have the advanced analytical capabilities needed to get the maximum value from data sources. As a result, the labs collect data, but the data does not get used properly to generate insights that could prevent problems or reduce testing volumes.

Spending too little time and effort on developing a robust change-management program. Digital transformation requires radical changes in mind-set and has major implications for the organization and individual employees who must develop new skills and competencies. To succeed, companies must make up-front investments in changing the culture, winning buy-in across the business, and forging strong links between business and IT functions.

Modern technologies can make QC faster, more agile and reliable, more compliant, and more efficient. By setting appropriate goals, choosing the right technologies, and scaling up quickly, pharma companies can become QC leaders and reap the rewards in the form of speed, compliance, cost savings, and productivity improvements.

Source: McKinsey & Company

27

Production Unit / Automation in Pharmaceutical Manufacturing

« Last post by LamiyaJannat on May 27, 2021, 08:09:22 PM »

Technological advancements open the door to fundamental performance improvements in pharmaceutical manufacturing.

The need for process optimization, regulatory compliance, and improvements in the supply chain are driving investment in automation technologies across the pharmaceutical industry. Consequently, the systems used to automate process steps during the manufacture of pharmaceuticals are continuously evolving with new instrumentation and control products coming to market.

This article will consider trends that impact the future of automation and what will likely be the biggest influences in transforming the pharmaceutical manufacturing environment.

Multi-Product Manufacturing Facilities

Gone are the days when manufacturing facilities could rely on developing the same product year after year. More targeted therapies that need to be manufactured in smaller volumes for smaller populations means the industry is seeing a transition away from “one-line-one-product” setups in favor of multi-product manufacturing facilities. These sites must be designed to be more agile, with the capability to react to changing demands quickly. The growing trend toward contract manufacturing is also driving the need for more flexible facilities to meet the needs of multiple customers.

Flexibility is key, and modern facilities need to be able to re-orientate their processes according to the requirements of individual products. As a result, sites are now being designed in a way that ensures a high degree of segregation between process steps, provides cross contamination control, and limits product exposure to the environment.

Single-Use Technologies

Aligned with today’s growing pipeline of high potency and biological drugs, the adoption of single-use technologies, such as single-use bioreactors and other unit operations, is having a significant impact on the way that automation is delivered. The integration of process control systems and manufacturing execution system (MES) solutions with start-to-finish technologies and single-use manufacturing platforms is helping the industry to deploy biopharmaceutical manufacturing with increased productivity and efficiency, and at a lower cost, which can significantly reduce the time-to-market for new products.

Both upstream and downstream manufacturing processes benefit from single-use systems. They reduce or eliminate the time required to perform cleaning and steaming, and they allow manufacturers to switch quickly from one product to another, or from batch to batch.

Single-use components are also an enabling technology for smaller scale production of biopharmaceuticals, including antibodies, proteins, vaccines, and cell therapies, which would otherwise be much more difficult to produce. In addition, as the world of gene therapy continues to evolve, the industry can expect to see even greater reliance on single-use technologies. However, as a starting point, many companies may in the first instance choose to pursue hybrid facilities with both stainless steel and single-use components.

Continuous Manufacturing

Batch manufacturing processes have a pre-defined maximum asset utilization on the plant floor. Traditional pharmaceutical companies have in the past been slow to investigate new manufacturing techniques, preferring a more risk-adverse approach to modifying the validated batch manufacturing design.

Cost pressures and the need to find ways to increase productivity have led to the introduction of new continuous manufacturing techniques across a number of unit operations in the life science industry. Oral solid dose tableting lines, continuous API production, and continuous chromatography in biological processes are but a few examples of where continuous manufacturing provides greater productivity for companies. With this also comes new challenges from an automation perspective, not only in the continuous manufacturing process but also in the batch record and genealogy requirements for the product.

Industry 4.0

Industry 4.0 is becoming increasingly important to the continued success and competitiveness of pharmaceutical manufacturers. It refers to new tools and processes that are enabling smart, decentralized production, with intelligent factories, integrated IT systems, the Internet of Things (IoT), and flexible, highly integrated manufacturing systems. For the life science manufacturing industry, it’s not about being new—it’s about using proven solutions and approaches to decision making to improve quality, reliability, and reducing waste. Companies in the life science industry have been collecting and using evidentiary data to improve their manufacturing processes for nearly 40 years and have some of the best quality systems in the world.

Industry 4.0 is simply the latest wave of technological advances that will drive the next phase of pharmaceutical manufacturing. It will enable manufacturers to have full visibility of operations and allow them to be responsive to information, while bringing connectivity of equipment, people, processes, services, and supply chains. Industry 4.0 will take automation to a new level with individual management processes expected to become automated. For example, if a temperature gauge makes a higher than expected reading, the machine will detect this and rectify the situation rather than requiring an operator to intervene and make an assessment about the required course of action.

In addition, future developments may mean that machine learning algorithms will be able to adjust manufacturing lines and production scheduling quickly. New developments will also pave the way for predictive maintenance and the opportunity to identify and correct issues before they happen.

The food and drinks industry is leading the charge in implementing Industry 4.0, with some companies in the sector beginning to use artificial intelligence to improve processes. Similarly, the automotive industry is also making considerable progress in terms of smart devices, the IoT, and achieving connectivity between all systems within a manufacturing plant.

Due to regulatory constraints, the pharmaceutical industry has been slower to adopt this type of cutting-edge technology. While embracing the potential for Industry 4.0 is going to be critical to future operational efficiency for all manufacturers, it may be a long time before the industry is able to complete the digital transformation and have fully automated and connected facilities that can take advantage of all the age of digital manufacturing has to offer.

Leveraging Data & Analytics

While the idealistic end game of fully connected, self-optimizing production processes may be further down the road, the first steps to digital manufacturing are well under way. Automation and technology create the opportunity to leverage data and analytics to improve processes. Often referred to as enterprise Manufacturing Intelligence (MI), access to more meaningful data means a better view of operations, allowing for better analytics and real-time responsive decision-making to drive continuous improvement and operational excellence.

With Industry 4.0 comes the introduction of edge devices; computing to make it easier to connect machines and the ability to create organization-wide data lakes. These edge devices can also be used to run analytics in real time close to the equipment while big data is analyzed in the cloud.

Big data also allows for the creation of digital twins. A digital twin can be made up of end-to-end data in the manufacture of a product where a fleet’s data can be used to find insights. Extension of the traditional “golden batch,” where data was very much process control-based, will be supplemented and surrounded with environmental data, raw material data, training data, and any other digital data available that goes toward influencing the golden batch. With this digital information available across multiple sites, batches and suppliers, sophisticated advanced analytics can provide a digital twin that best represents the golden batch and alert controllers to any problems based on these specific data sets.

Final Thoughts

Automation and other manufacturing systems, such as MES, have the potential to transform processes within pharmaceutical manufacturing facilities, opening the door to fundamental performance improvements. For manufacturers that fail to leverage these technologies, the introduction of new pharmaceutical products may take months or years rather than weeks, and they will likely find themselves falling behind their competitors in the efficiency stakes. Companies that take the initiative early stand to gain the biggest competitive advantage, ensuring they can operate with greater agility, cost-efficiency and compliance. 

Written By-
Trevor Marshall
Director of Enterprise System Integration,
Zenith Technologies

28

Technology / Drugs on Demand: How Automation is Changing the Global Pharma Industry

« Last post by LamiyaJannat on May 27, 2021, 07:46:02 PM »

The global pharmaceutical industry has traditionally been a complex and difficult space to master. Tasked with serving the health needs of millions of patients with varied afflictions, the industry must constantly meet stringent regulations and compliance standards. One wrong move can set in motion a free falling chain of events. Moreover, manufacturers are constantly working to achieve control and transparency across facilities as rising R&D costs lead to higher drug prices.

Pharmaceutical manufacturing has evolved drastically since the days of the apothecaries and wholesale production in the 19th century. Today, drug makers have mammoth state-of-the-art manufacturing facilities that are driven by robotics, AI and cutting-edge tech-enabled business processes, in alignment with Good Manufacturing Practices (GMP) and U.S. FDA regulations. Recipe processes now go through multiple automated stages as the industry transitions from batch to continuous manufacturing.

Automation is definitively transforming pharma, with regard to product development, commercial production and real-time monitoring. It can foster manufacturing excellence by leveraging sensors and identification systems to not just help companies achieve compliance, but also to do so at the lowest costs. Indeed, many pharma manufacturers have deployed Corrective Action, Preventive Action (CAPA) software to adhere to GMP and FDA norms.

In the digital era, compliance-as-a-service is expensive, but non-compliance is even more so due to the underlying hidden costs. Companies are racing to compete with generics before their product patents expire, so they are turning to automation to boost speed-to-market. Doing so also leads to associated benefits such as product yield improvement, less wastage, greater adherence to safety and environmental controls. All these translate into cost savings for patients.

Quality compliance and cost savings with robotics and AI

Pharma companies are increasingly partnering with external solution vendors to integrate robotics into specific processes concerning drug development, manufacturing and anti-counterfeiting. Operating in an intensely regulated marketplace, drug makers must meet the various guidelines and recommendations outlined for ensuring public health safety. Therefore, they are opting for automated setups and tools that enable effective risk management and greater scalability.

Automation is firmly embedded in primary aspects such as Active Pharma Ingredients (API) and in myriad other secondary aspects including packaging and distribution. As medicines exist in either solid or liquid state, automated manufacturing techniques can master the weighing, blending and tableting of solids, or the stirring and filling of liquids, to deliver global standardization. This new-found precision in laboratory manufacturing is also driving the discovery of new medicines, further boosting the adoption of digital manufacturing.

Another area where automation is having a massive impact is in the supply chain and logistics domain. Thanks to the growing adoption of RFID technologies, electronic batch records and workflow management, medicine delivery has become more effective. Errors and weaknesses in the logistics system can easily be spotted and removed. Thus, the right medicines can now reach the neediest people at the right time, thanks to the help of complex algorithms that can predict the same.

The increased use of robots in pharma manufacturing is also prevalent in processes related to dispensing, kit assembly, sorting and machine tending. These automated processes are teaming up to offer the industry more flexibility, greater speed and lower operating costs. Moving forward, greater integration between development work and manufacturing will be possible. And, it will all work together to reduce the primary cause of error in manufacturing processes–human error.

Bright future for pharma regulatory compliance

Pharma companies are thus looking to integrate the benefits of shared support services and shared environments to reap the benefits of automation now. This can be done firstly by establishing Centers of Excellence (CoE) that enhance each step of the automation process, and by optimizing the usage of data collected through sensors. Doing so can ensure that all the data produced and collected is compliant from a regulatory perspective. This data can increasingly be used for proactive reporting of safety and information management to give pharma companies a holistic approach toward complete enterprise-wide Governance, Risk and Compliance (eGRC).

The FDA is further putting in place guidelines and rules that can pave the way for drug manufacturers to adopt modern technologies that can boost quality. Quality by design and adopting a risk-based approach to automation are just key first steps to help manufacturers head in this direction and deliver the best medicines.

Written By:
Diti Rastogi,
Senior Business Consultant - Life Sciences

29

Antipyretic / Study of potential toxic effects of acetylsalicylic acid upon short-term repeate

« Last post by LamiyaJannat on May 27, 2021, 01:48:06 PM »

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are used commonly for the treatment of various musculoskeletal inflammatory disorders in human and veterinary practice. In veterinary medicine, they are used to overcome certain clinical conditions like spondylitis, laminitis, mastitis, endotoxic shock and colic in the horse and for the control of pain associated with trauma or surgery (Boothe 2001). Similar to mammals, prostaglandins are involved in the modulation of pain responses in birds (Nicol et al. 1992). Besides, NSAIDs are also indicated in birds (Bauck 1990) that are very much essential to manage pain and inflammatory conditions in food-producing birds (chickens, ducks, turkeys, geese, swans, quails, guinea fowls, ostrich, emu, etc), pet birds as well as in zoo birds (Mohan 2010). Although a large number of NSAIDs are being discovered following the initial breakthrough of aspirin, comparatively a very small number of NSAIDs are being used in birds unlike in other domestic animals or human beings. Sodium salicylate and acetaminophen found to possess anti-nociceptive properties in pigeons (Brune et al. 1974). Acetylsalicylic acid was used in duck production for tenosynovitis and in turkey industry for certain leg problems (Jouglar and Benard 1992). A moderate reduction in ascites was reported for acetylsalicylic acid treated broiler chickens kept in a hypobaric chamber to mimic high altitude (Balog et al. 2000). Self-selection of feed containing an analgesic drug, carprofen was found much higher in lame broiler chickens than sound birds (Danbury et al. 2000). Supplementation of acetyl salicylic acid at a rate of 20 ppm to layer diets during summer season improved both production and reproduction performance (Galil 2004). The findings of these studies suggest that the prostaglandins and cyclooxygenases (COXs) participate in avian nociception and as a result, the use of NSAIDs has found to produce analgesia in birds (Machin et al. 2001). Acetylsalicylic acid, popularly known as aspirin, is commonly used in human medicine. Since this drug is easily available at over the counter, there is all likelihood that pet owners, sometimes caretakers of pet birds and veterinarians use this drug for treating certain clinical conditions (febrile status, joint-related problems and other inflammatory conditions) in birds. Although usage of acetylsalicylic acid is suggested in birds nevertheless, the studies relating to the potential toxic effects of this drug upon repeated oral administration in birds are rarely reported. Hence, the present study was designed to assess the toxic effects of acetylsalicylic acid in chickens.

Materials and methods

Experimental birds
Twenty apparently healthy, unsexed broiler chickens, aged five weeks with body weight ranging from 1.4 to 1.6 kg procured from commercial poultry farm were used for the study. Live bird procedures used in this study were approved by the University Institutional Animal Ethics Committee (IAEC). All the birds were caged individually in experimental animal house maintained under standard laboratory housing conditions. Medication-free feed (free from any antibiotics or coccidiostats) procured from the university poultry farm was fed ad libitum with free access to potable water. All birds were acclimatised to the laboratory housing condition for a period of five days.

Drug formulations

During the experimental period, fresh acetylsalicylic acid solution was prepared daily. The amount of acetylsalicylic acid required to prepare the formulation was based on the body weight of birds. The calculated amount of acetylsalicylic acid (Sigma–Aldrich, St. Louis, MO, USA) was dissolved in the Milli-Q water using an ultrasonicator (Powersonic-410, Daichen Labtech Co. Ltd., Korea).

Dose fixation

The dosage regimens reported for treatment in domestic chickens are mostly extrapolated from other species or sometimes identical to that of small mammals. Therefore, in view of the above premise and in order to evaluate the potential toxic effects of acetylsalicylic acid, the dose of 10 mg/kg (Thompson 2008) (therapeutic dose for small animals) was selected.

Experimental design

Twenty broiler chickens were randomly divided into two groups of 10 birds in each group (completely randomised design). The gavaging tubes of 10 cm length prepared from infant feeding tube fixed to two milliliter syringes were used to deposit the drug formulation directly into the crop of individual bird. Group I served as control and received Milli-Q water (1.0 ml/day, p.o.) and group II received acetylsalicylic acid (10 mg/kg/day, p.o.) at an interval of 24 h for a period of 5 days. After dosing, general clinical observations were made twice daily throughout the study period and birds were observed for general health condition, morbidity and mortality, if any, were recorded.
Blood sampling and analysis

The blood samples were collected from cutaneous ulnar vein by using two millilitre disposable syringe and needle (22 G, 1.5” length). The blood samplings were performed prior to treatment on day 1 and on subsequent days at 24 h interval for the period of five days. From each bird, approximately 1.5 ml blood was collected. From this, 0.2 ml blood was transferred to 1 ml storage vials containing 500 µg of Na2EDTA and this was used for estimation of total erythrocyte count (TEC), haemoglobin concentration (Hb), packed cell volume (PCV) and platelet count by using fully automatic blood cell counter (Model PCE-210, Erma Inc., Tokyo, Japan).

The left-over blood in the syringe was transferred to clean, dry 3 ml glass tubes. The blood in the glass tubes was allowed to clot. Serum was separated from the clotted blood following centrifugation at 2500 rpm for 10 min at room temperature. The serum was transferred to storage vials of 1 ml capacity and stored at −20°C. The serum samples were analysed for aspartate aminotransferse (AST), alanine aminotransferase (ALT), creatinine, uric acid and total serum protein using commercially procured diagnostic kits from Merck (Ecoline®, Merck Specialties Limited, Kalyan Badlapur Road, M. I. D. C Area, Ambernath, India) by utilizing clinical chemistry analyzer-Microlab 300 (Vitalab Scientific, The Netherlands).

Specimen collection and processing

On day 6, all birds were subjected to detail necropsy and gross pathological changes if any were recorded. For histological examination, a representative tissue samples from proventriculus, small intestine, liver and kidney were collected in 10% neutral buffered formalin. They were processed by routine paraffin embedding technique and sections of 5 µ thicknesses were cut and stained by haematoxylin and eosin (Luna 1968).
Statistical analyses

The data were subjected to statistical analysis. Mean values and standard error of mean were calculated and all the values were expressed as Mean±SEM. The data were analysed by student's t-test using statistical software, GraphPad Prisim (2004) and P<0.05 was considered as significant.

Results and discussion

Group II birds showed clinical signs of toxicity such as hypo activity and disinclination to move. These clinical signs were observed 2–3 h after daily dosing. In addition, they showed watery droppings accompanied with blood mixed mucous from day 3 onwards.

Significant (P<0.05) reduction in the TEC on day 4 and 5, haemoglobin concentration, PCV and platelet count on day 3, 4 and 5 was observed in the group II compared to group I (Table 1). Significant (P<0.01) decrease in serum total protein concentration on day 4 and 5 was observed in group II compared to group I (Table 2). At necropsy, group II birds showed severe congestion on serosal surface of small intestine, petechial haemorrhages were observed on mucosal surface of ceca. On microscopic examination of proventriculus sections of group II birds showed haemorrhages on the sub-mucosa or lamina propria, hyalinisation of villus epithelium accompanied with infiltration of inflammatory cells. Sections of small intestine showed erosion, haemorrhages on the sub-mucosa or lamina propria and desquamation of villus epithelium into the lumen with infiltration of inflammatory cell. No apparent
The clinical signs of toxicity viz. hypo activity and disinclination to move observed in group II birds were associated with acetylsalicylic acid-induced toxicity and these toxic clinical signs found to be transitory and descended over a period of time (6–7 h after dosing). To correlate, NSAID-induced clinical signs of toxicity were also observed in the broiler chickens (Mohan et al. 2012) and Leghorn layers, 24 h post administration of diclofenac, wherein the affected birds appeared comatose and could not arouse (Naidoo et al. 2007).

The significant reductions in the TEC, haemoglobin concentration and PCV per cent of the blood samples observed in group II birds are attributed to the adverse effect exerted by this drug on haematopoietic system. The major function of the red blood cells is to transport haemoglobin, which in turn carries oxygen from the lungs to the tissues (Waugh and Grant 2001). Reduction in the haemoglobin is accompanied by a fall in the erythrocytes and PCV (Waugh and Grant 2001). Very low readings for TEC, haemoglobin concentrations and PCV per cent observed for group II birds are indication of anaemia due to heavy loss of erythrocytes on account of haemorrhage in the gastrointestinal tract.

Avian thrombocytes play a primary role in haemostasis in a manner similar to mammalian platelets. They also have a phagocytic function and participate in removing foreign material from the blood (Dieterlen-Lievre 1988; Campbell 1988). A normal thrombocyte count ranging between 20,000 and 30,000/µl of blood is used as a general reference for most of the birds (Jain 1993). Thrombocytopenias are usually indicative of excessive peripheral demand for thrombocytes, although a depression in thrombopoiesis should be considered (Campbell 1988). Thrombocytopenias are often seen in conditions where a combination of excessive peripheral demand for thrombocytes and in case of decreased thrombocyte production. A thrombocytosis may reflect a rebound response following haemorrhage or recovery from other conditions associated with excessive utilisation of thrombocytes (Campbell 1997). The significant reduction in the platelet count in blood samples observed on day 3, 4 and 5 in group II birds are due to impair platelet activity caused by impaired thromboxane synthesis. Particularly, acetylsalicylic acid irreversibly acetylates the platelet cyclo-oxygenase. Since, platelets unable to regenerate cyclo-oxygenases, platelet aggregation defects caused by acetylsalicylic acid found to last up to one week (Eyre and Burka 1979).
The most predictable and serious adverse effects associated with NSAIDs has reported in the gastrointestinal tract (Curry et al. 2005). Gastrointestinal perforation, ulceration and bleeding have been associated with NSAID-induced depression of normal PGE2 mediated and mucosal protective mechanisms (e.g., bicarbonate and mucous secretion, epithelialisation and maintenance of mucosal blood flow) (Bertolini et al. 2001). In the present study, toxic clinical signs such as blood and mucous mixed diarrhoea and lesions observed on the mucosa of intestine and ceca of the birds administered with acetylsalicylic acid are mainly due to the disruption of normal integrity of gastrointestinal mucosa largely mediated by inhibition of COX1 activity.
Non-steroidal anti-inflammatory drugs are well recognised for having potentially toxic effects on the gastrointestinal tract, which may lead to diarrhoea. The prostaglandins PGE2 and PGI2 are critical for the maintenance of normal mucosal blood flow within the gastrointestinal tract (Boothe 2001). Marked decrease in serum total protein concentration is suggestive of gastrointestinal and hepato-toxicity (Denman et al. 1983; Lumeij 1999). To corroborate, severe congestion and haemorrhages observed in the small intestine of group II birds was due to inactivation of the COX (cyclo-oxygenase) enzymes by acetylsalicylic acid. The inactivation of COX leads to a decrease in prostaglandin production, which, in turn, impairs mucosal blood flow and leads to mucosal inflammation and injury leading to protein loosing enteropathy (Boothe 2001). Thus, marked reduction in serum protein observed in group II attributed to the toxic effect exerted by acetylsalicylic acid on gastrointestinal tract.

Conclusion
In conclusion, acetylsalicylic acid at 10 mg/kg upon repeated oral administration daily for a period of five days found toxic in chickens.

Source: Journal of Applied Animal Research

30

Article / Solutions and Treatments

« Last post by LamiyaJannat on May 27, 2021, 01:32:08 PM »

Solutions and Treatments

The following solutions have been used as supportive treatments by poultry and game bird producers. They are intended as aids in treating the described conditions, not as a replacement for any management, drug, or antibiotic therapy.

ASPIRIN SOLUTION

Used as a general treatment for reducing distress conditions of birds (fever or listlessness) that accompanies many diseases.

    Dissolve five (5 grain) aspirin tablets in one gallon of water.

Offer this solution free-choice to the birds for the duration of an illness. The solution aspirin equivalent to 25 grains/gallon or 324 mg/gallon of drinking water. The dosage rate is about 25 mg/lb body weight per day.


ASTRINGENT SOLUTION

This solution can be used to treat young birds that show non-typical disease symptoms of poor growth. The solution can also be given to birds suffering from respiratory diseases that produce a large amount of mucus exudate. This solution will help "cut through" the mucus and allow it to be expelled easier.

    Two quarts of apple cider vinegar diluted into 100 gallons of water
    (4 teaspoons/gallon)

The tannin in the apple cider vinegar aide in removing any mucus or coating from the mouth, throat, or intestinal tract. Nutrients and drugs are more readily absorbed. Offer this solution as the only drinking water source for two to three day intervals.

COPPER SULFATE SOLUTION

Use this solution as a treatment for mycosis (mold infection) in the crop. An alternate name for the condition is "Thrush." Use the solution as a "follow-up" treatment after flushing with epsom salt solution--refer to the section for LAXATIVE SOLUTIONS.

    Dissolve .5 lb copper sulfate and .5 cup vinegar into 1 gallon of water for a "stock" solution. Dispense stock solution at the rate of 1 oz per gallon for the final drinking solution.

An alternate method of preparing the solution is:

    dissolve 1 oz copper sulfate and 1 tablespoon of vinegar into 15 gallons water.

Use either solution as the sole water source during the course of the disease outbreak. Copper sulfate is often referred to as "bluestone".

EGG DIPPING SOLUTION

This procedure has been used to destroy pathogenic organisms such as Mycoplasma spp. that can be carried on the hatching eggs. The procedure must be conducted exactly as described, and is not intended as a routine hatching egg treatment. The procedure is only used in unusual situations.

    The antibiotic solution contains 500 ppm gentamycin sulfate
    (1 gram per 2 liters of water) or 1 gram tylosin per liter of water.

The hatching eggs must be carefully washed, rinsed, and sanitized prior to treatment. The eggs are then prewarmed to 100 degrees F. for 3-6 hours and immediately submerged into the antibiotic solution that has been previously cooled to 60 degrees F. The eggs are left in the antibiotic solution for 15 minutes before being placed into the incubator.

After each day's use, the solution must be sterilized by heating to 160 degrees and maintained for 10 minutes. Any water lost during sterilization must be replaced. Refrigerate the solution in a clean covered container between uses to prevent bacterial contamination. Do not use or store solutions for more than three days after dilution.

FUMIGATION OF HATCHING EGGS AND EQUIPMENT

Preincubation of hatching eggs and equipment

    Mix .6 gram potassium permanganate (KMnO4) with 1.2 ml formalin for each cubic foot of space.
    -or-
    2 oz KMnO4 and 4 fl oz formalin per 100 ft3 space.

Mix both ingredients in an earthenware or heat resistant container having at least ten times the capacity of the ingredients being added. Circulate the gas for 20 minutes at 70 degrees F. or higher. Equipment without eggs can be allowed to fumigate overnight before exhausting the formaldehyde gas.

Fumigating eggs in incubator

    Mix .4 gram KMnO4 and .8 ml formalin per ft3
    -or-
    1.5 oz KMnO4 and 3 fl oz formalin per 100 ft3

Follow the same guidelines as discussed for equipment fumigation. Do not fumigate chicken eggs between the 24th and 96th hours of incubation. Other species of birds may need the incubation intervals adjusted to compensate for total incubation time in relationship to the chicken's incubation period. It is best to incubate after the incubator reaches normal operating temperature and humidity.

LAXATIVE SOLUTIONS

The following solutions or mixtures are recommended to flush the digestive system of toxic substances, most notably for treating birds exposed to botulism toxins.

Molasses Solution

    Add one pint of molasses to 5 gallons of water

Offer the drinking solution free-choice to the affected birds for about four hours. Treat severely affected birds individually if they cannot drink. Return the birds to regular water after the treatment period.

As a supportive treatment for symptoms resulting from Cryptosporidia infection, often referred to as coronaviral enteritis, use:

    One quart molasses in 20 gallons of water

Offer this solution free-choice for a period of up to 7-10 days. It is assumed that the molasses replaces certain minerals lost from diarrhea during the course of the infection.

Epsom Salt Solution

    1 lb Epsom Salt per 15 lb feed
    -or-
    1 lb Epsom Salt per 5 gallons water for 1 day

Give the epson salt feed mixture as the sole feed source for a one day period. This feed can be used only if the birds are eating. If the birds are not eating, use the water solution. If the birds are unable to eat or drink by themselves, use individual treatment with:

    1 teaspoon of Epsom Salt in 1 fl oz water

Place the solution in the crop of the affected bird. This same amount of solution will treat 5-8 quail or one chicken.

Castor Oil Therapy

    Dose individual birds with .5 oz castor oil.

NUTRIENT SOLUTIONS

The following solutions can be used as supplements to diets that are deficient in certain amino acids, energy, or vitamins and electrolytes. They are used only as temporary additives and not intended as part of a regular feeding program.

Amino Acid Solution

    100 grams (7 fl oz) dl-methionine and 110 grams (6 fl oz) l-lysine HCl dissolved in 50 gallons water
    -or-
    2 grams (.8 tsp) dl-methionine and 2.2 grams (.7 tsp) l-lysine HCl in one gallon of water

Offer the solution free-choice to the birds as an aide to reducing the depressing effects of low-protein diets. Make up a fresh solution daily and offer to birds in clean waterers. All measurements in parentheses () are volumetric measurements while those expressed in grams are weight measurements.

Sucrose Solution

    10 ounces of granulated sugar per gallon of water

This solution may be given as an energy treatment for weak chicks. Offer the solution as the only water source for the first 7-10 days. Clean the drinkers and replace with fresh solution at least once daily. The solution shown above contains eight percent sugar and approximately 2000 kilocalories per gallon.

Vitamin & Electrolyte Solution

This solution can be used to reduce the effects of stresses caused by subclinical diseases, transporting, management errors, etc. Dilute a commercial vitamin/electrolyte packet into the prescribed amount of water. Use as the only source of drinking water until the stress problem has been corrected.

PARASITE (INTERNAL) SOLUTIONS

The following treatments have been shown to be effective for eliminating internal parasites from poultry and game birds. Neither of these drugs (fenbendazole or leviamisole) has been approved for use by FDA, so the producer accepts all responsibility for their use. Both drugs have been very effective if used properly and will eliminate most types of internal parasites that affect birds. Caution: Do not use with birds producing eggs or meat destined for human consumption.

Fenbendazole Treatments

One-day Treatment

    1 oz Safeguard or Panacur per 15-20 lb feed

Dissolve the fenbendazole product in one cup of water. Mix this solution well into the feed and give to the birds as their only feed source for one day. When completely consumed, untreated feed can be given. Be sure that the commercial medication contains 10% fenbendazole.

Safeguard is a product of Ralston Purina, and Panacur is a product marketed by American Hoechst. One ounce of medication will treat about 1000 10-oz bobwhite quail. Adjustments of the amounts of medication and feed needed may be necessary depending on the number and size of the birds.

Three-Day Treatment

    1.2 oz Safeguard or Panacur in 100 lb feed
    -or-
    4 oz pkt of "Worm-A-Rest Litter Pack" (Ralston Purina) in 50 lb feed
    -or-
    5 lb bag of "Worm-A-Rest Mix Pack" in 495 lb feed

Feed all the medicated feeds free-choice for three consecutive days. The feed mixtures provide 75 ppm fenbendazole. Quail will receive about 1.7 mg/bird each day for adult birds or 2.75 mg/lb of bodyweight.

Fenbendazole has been shown to be a very effective treatment for eliminating Capillaria (capillary worms), Heterakis (cecal worms), Ascaridia (roundworms), and Syngamus spp. (gapeworms). Toxicity from overdosing with fenbendazole is very remote. Research indicates that amounts up to 100 times the recommended dosages have been given under research conditions without adverse effects to the birds. Use of this product during molt, however, may cause deformity of the emerging feathers.

Leviamisole Solutions

    52 gram (1.84 oz) pkt Tramisol in 100 gallons water
    -or-
    13 gram (.46 oz) pkt Tramisol in 25 gallons water
    -or-
    52 gram (1.84 oz) pkt in 3 qt water (stock solution)

Dissolve the 52 gram packet of "Tramisol Cattle and Sheep Wormer" or the 13 gram packet of "Tramisol Sheep Drench Powder" into the appropriate amount of water. If the stock solution is used with a water proportioner, be sure that the stock solution is dispensed at the rate of 1 oz/gallon in the drinking water.

Any of the solutions are effective at treating Capillaria (capillary worms), Heterakis (cecal worms), and Ascaridia (roundworms). The solutions contain .5 gram of leviamisole per gallon of water. Allow the birds to drink the solution for one day, then remove. In severe cases, the treatment can be repeated every 5-7 days.

PESTICIDE SOLUTIONS

Mite and Lice Body Spray Solution

Dissolve into 10 gallons of water:

    6.5 fl oz 10% Permethrin EC
    -or-
    11.5 fl oz 5.7% Permethrin EC
    -or-
    2.5 fl oz 25% Permethrin EC
    -or-
    1.5 lb 25% Malathion wettable powder
    -or-
    5.3 oz 57% Malathion EC
    -or-
    .75 lb 50% Carbaryl (Sevin) wettable powder

Spray birds thoroughly to wet the skin and feathers. Pay particular attention to the vent area of the birds. Each gallon of spray will treat 75-100 adult leghorn-type laying hens or 250-300 adult quail. A second treatment can be applied about four weeks after the first application if necessary. The walls, ceiling, and litter of the house can be sprayed with these solutions to kill individual insects not on the birds.

Mites, Lice, and Housefly Residual Spray

Dissolve one of the following in 10 gallons of water.

    1 quart 5.7% Permethrin EC
    -or-
    1 pint 10% Permethrin EC
    -or-
    6 oz 25% Permethrin wettable powder
    -or-
    3 lb 25% Malathion wettable powder
    -or-
    10 fl oz 57% Malathion EC

Apply the permethrin spray to all ceilings, walls, roosts, nests, cracks, and crevices at the rate of one gallon for every 750 square feet. One application will be effective for at least three weeks.Malathion sprays are used as residual sprays to ceilings, walls, roosts, litter, and any dark location that is difficult to reach. Malathion sprays are applied at the rate of one gallon for every 500-750 square feet. Malathion is not recommended for fly control, but is usually effective when used in combination with body sprays for mites and lice.

SANITIZING SOLUTIONS

These solutions will reduce or eliminate slime and most disease organisms in water, drinkers, and water lines.

For Constant Use

    1 teaspoon chlorine bleach (sodium hypochlorite) in 5 gallons of drinking water

This solution provides 11 ppm chlorine for sanitizing. The birds will drink the water and not be harmed by drinking it. They may need a short time to become accustomed to this solution. A more dilute solution with half the above level of bleach can be offered for a few days before using the 11 ppm solution. Clean the waterers thoroughly each day to get the best effect.

Weekly Sanitizing Rinse Solution

    1 oz Chlorine Bleach in 6-8 gallons water

Rinse, soak, or expose equipment to this solution. Let stand at least one hour, then rinse with fresh water. This solution contains equivalent to 45 ppm chlorine. The procedure is most effective if conducted on a weekly basis. Remember, chlorine disinfectants are inactivated by organic matter. Clean all equipment well before using chlorine rinse solutions.

VACCINE ADMINISTRATION GUIDELINES

Clean waterers prior to vaccination. Deprive the birds of drinking water beginning one hour in hot weather and two hours in moderate or cold weather. Mix 3.2 oz powdered skimmed milk packet or equivalent into ten gallons of water. The milk neutralizes the small amount of chlorine or sanitizer present in many water sources.

Follow the vaccine manufacturer's mixing instructions for dilution level. Administer vaccine-water solution in the waterers immediately after mixing. All the vaccine solution must be consumed within 15-20 minutes if good immunization is expected.

Source: Mississippi State University Division of Agriculture, Forestry and Veterinary Medicine