1. Contaminated pharmaceutical products can present health hazards ranging from local infections to life-threatening systemic infections depending on the type and amount of contamination as well as the patient's susceptibility.
2. Gram-negative bacteria are a particular concern as they have caused numerous outbreaks through contaminated products and can produce endotoxins. Routes of administration like ophthalmic and parenteral introduce the highest risk.
3. The effects of contaminated product use may vary between patients depending on the microbial contaminant, administration route, and individual patient resistance and immune status. Immunocompromised patients are most at risk.
Fermenters, also known as bioreactors, are closed containers used for culturing microorganisms or cells under controlled conditions. There are several types of fermenters including stirred tank, airlift, bubble column, packed bed, and fluidized bed fermenters. Fermenters provide aeration, agitation, temperature and pH control to microorganisms. They are used across various industries like food processing, pharmaceuticals, and waste treatment. Modern fermenters are integrated with sensors and computers to monitor processes efficiently.
Biosafety aims to prevent large-scale biological harm to both the environment and human health. It involves regularly reviewing safety protocols in laboratories working with biological materials. Risks arise from the samples and equipment used, and can threaten both workers and the outside community if safety regulations are not followed. Proper risk assessment of pathogens considers factors like infectiousness, transmission methods, treatment options, and containment facilities available.
The document discusses various topics related to fermentation and inoculum development. It begins by defining fermentation as a metabolic process that consumes sugar in the absence of oxygen, producing organic acids, gases, or alcohol. It then discusses inoculum development, noting it is the process of developing an active microbial culture suitable for industrial fermentation. This involves building up the culture volume gradually while maintaining genetic uniformity. Finally, it provides details on developing inocula for different types of microorganisms, including unicellular bacteria, mycelial fungi, and vegetative fungi. It emphasizes the inoculum must be in a healthy, active state with sufficient volume while being free of contamination.
This document discusses various methods for sterilizing gases, liquids, and equipment in bioprocess technology. It describes how sterilization of inlet gases can be achieved through absolute, ceramic, fibrous and stainless steel filters, as well as filter cartridges and membrane filters. It also discusses liquid sterilization using filtration and heat sterilization methods. Sterilization techniques for small equipment include the use of microbiocidal gases, chemicals, radiation and dry heat. Methods for sterilizing large industrial equipment involve valves, piping and eliminating condensation. Validation of sterilization processes is also covered.
Anti-foaming agents, inducers, precursors and inhibitors in Fermentation tech...Dr. Pavan Kundur
The document discusses antifoaming agents, inducers, precursors, and inhibitors used in fermentation technology. Antifoaming agents like oils and silicones are added to fermentation to reduce foam formation which can contaminate processes. Precursors are added to increase product yields, like corn steep liquor for penicillin production. Inducers trigger secondary metabolite production in microbes and are necessary for genetically modified organisms. Inhibitors redirect metabolism toward the target product or halt pathways to prevent degradation.
A fermentor, also known as a bioreactor, is a closed vessel used for commercial fermentation processes. It provides controls for factors like temperature, pH, aeration and agitation to maintain optimal conditions for microbial growth. Early large-scale fermentors had capacities over 20 liters and were used to produce products like yeast and acetone. Modern fermentors can be designed as various types depending on the application, including stirred tank, airlift, photo and fluidized/packed bed bioreactors. Proper design of components like the vessel material, agitator, sparger and temperature/pH controls is important for efficient fermentation.
Industrial sterilization will help you to get more information about sterilization in pharmaceutical industries. how the process of sterilization are selected for different product.
Fermenters, also known as bioreactors, are closed containers used for culturing microorganisms or cells under controlled conditions. There are several types of fermenters including stirred tank, airlift, bubble column, packed bed, and fluidized bed fermenters. Fermenters provide aeration, agitation, temperature and pH control to microorganisms. They are used across various industries like food processing, pharmaceuticals, and waste treatment. Modern fermenters are integrated with sensors and computers to monitor processes efficiently.
Biosafety aims to prevent large-scale biological harm to both the environment and human health. It involves regularly reviewing safety protocols in laboratories working with biological materials. Risks arise from the samples and equipment used, and can threaten both workers and the outside community if safety regulations are not followed. Proper risk assessment of pathogens considers factors like infectiousness, transmission methods, treatment options, and containment facilities available.
The document discusses various topics related to fermentation and inoculum development. It begins by defining fermentation as a metabolic process that consumes sugar in the absence of oxygen, producing organic acids, gases, or alcohol. It then discusses inoculum development, noting it is the process of developing an active microbial culture suitable for industrial fermentation. This involves building up the culture volume gradually while maintaining genetic uniformity. Finally, it provides details on developing inocula for different types of microorganisms, including unicellular bacteria, mycelial fungi, and vegetative fungi. It emphasizes the inoculum must be in a healthy, active state with sufficient volume while being free of contamination.
This document discusses various methods for sterilizing gases, liquids, and equipment in bioprocess technology. It describes how sterilization of inlet gases can be achieved through absolute, ceramic, fibrous and stainless steel filters, as well as filter cartridges and membrane filters. It also discusses liquid sterilization using filtration and heat sterilization methods. Sterilization techniques for small equipment include the use of microbiocidal gases, chemicals, radiation and dry heat. Methods for sterilizing large industrial equipment involve valves, piping and eliminating condensation. Validation of sterilization processes is also covered.
Anti-foaming agents, inducers, precursors and inhibitors in Fermentation tech...Dr. Pavan Kundur
The document discusses antifoaming agents, inducers, precursors, and inhibitors used in fermentation technology. Antifoaming agents like oils and silicones are added to fermentation to reduce foam formation which can contaminate processes. Precursors are added to increase product yields, like corn steep liquor for penicillin production. Inducers trigger secondary metabolite production in microbes and are necessary for genetically modified organisms. Inhibitors redirect metabolism toward the target product or halt pathways to prevent degradation.
A fermentor, also known as a bioreactor, is a closed vessel used for commercial fermentation processes. It provides controls for factors like temperature, pH, aeration and agitation to maintain optimal conditions for microbial growth. Early large-scale fermentors had capacities over 20 liters and were used to produce products like yeast and acetone. Modern fermentors can be designed as various types depending on the application, including stirred tank, airlift, photo and fluidized/packed bed bioreactors. Proper design of components like the vessel material, agitator, sparger and temperature/pH controls is important for efficient fermentation.
Industrial sterilization will help you to get more information about sterilization in pharmaceutical industries. how the process of sterilization are selected for different product.
Preparation and quality control of immunological productsMayur D. Chauhan
The following presentation is only for quick reference. I would advise you to read the theoretical aspects of the respective topic and then use this presentation for your last minute revision. I hope it helps you..!!
Mayur D. Chauhan
Microbial Culture Preservation and its MethodsDENNISMMONDAH1
This document discusses various methods for preserving microbial cultures, including short term and long term methods. Short term methods include periodic transfer to fresh media, preservation using saline suspension, drying, and refrigeration. Long term methods discussed are preservation using liquid paraffin/mineral oil, glycerol, lyophilization (freeze drying), and cryopreservation in liquid nitrogen. The aim of preservation is to maintain cultures in viable condition for extended periods without genetic changes.
This document discusses sterilization of air and media. It defines sterilization as removing microorganisms through chemicals, heat, or radiation. For air sterilization, common methods are heating, radiation, chemicals, and filtration. Filtration uses depth or absolute filters to trap particles. Media sterilization can be in-situ or ex-situ. Common media sterilization methods are heat (such as autoclaving or steam), filtration, radiation (ionizing or non-ionizing), and chemicals (like ethylene oxide gas). Heat sterilization via autoclaving is most widely used.
The document discusses different types of bioreactors used in fermentation technology. It describes continuous stirred tank reactors, bubble column bioreactors, airlift bioreactors, fluidized bed bioreactors, packed bed bioreactors, photo-bioreactors, tower bioreactors, and rotary drum reactors. For each type of bioreactor, it provides details on the design, functioning, applications and advantages. Continuous stirred tank reactors provide good mixing but are open systems, while bubble column and airlift bioreactors rely on the bubbling of gas to promote mixing and circulation of the medium.
The document discusses foodborne infections and intoxications. Foodborne infections occur when harmful microorganisms in contaminated food grow in the intestines and cause illness, while intoxications result from toxins produced by microorganisms or present in plants/seafood. Common bacteria that can cause infections include Salmonella, Listeria, Campylobacter, and viruses like Hepatitis A and parasites such as Giardia. Symptoms include diarrhea and vomiting. Prevention methods include proper food handling and cooking practices.
Fermentation is a metabolic process where organic compounds like carbohydrates are broken down by microorganisms to release energy without oxygen. It is used to produce a variety of foods, beverages, industrial products, and more. There are several types of fermentation including alcoholic, lactic acid, propionic acid, and butyric acid fermentations. Fermentation can occur via solid state or submerged cultures in different types of bioreactors. Key factors that control microbial growth during fermentation include nutrients, pH, temperature, water activity, and presence of other microorganisms. Proper isolation techniques are required to culture pure microbial strains.
This document discusses important microorganisms in food microbiology, focusing on molds and yeasts. It describes the general characteristics, morphology, cultural characteristics, and physiological characteristics of molds and yeasts. Some molds and yeasts of industrial importance are also outlined, including Aspergillus, Penicillium, and Saccharomyces. The criteria used to classify and identify molds is also summarized.
This document discusses methods for isolating and cultivating animal and plant viruses. There are three main methods for animal viruses: embryonated chicken eggs, tissue cultures, and laboratory animals. Embryonated chicken eggs are commonly used as they provide several inoculation sites and are economical. Tissue cultures include primary cell cultures from animal tissues, diploid cell strains with normal chromosome numbers, and continuous cell lines with abnormal numbers that can undergo infinite divisions. Laboratory animals like primates and small mammals are also used but their use is now limited. For plant viruses, whole plants, plant tissue cultures, and protoplast cultures are used, with protoplasts being a standard technique. Insect cell cultures can also be used
This document defines fermentation and fermenter. It then describes the key components of a fermenter:
1) The vessel, which is designed to carry out fermentation under aseptic and controlled environmental conditions. Vessels come in small-scale laboratory or large-scale industrial sizes.
2) An impeller that provides mixing for oxygen transfer, heat transfer, and maintaining a uniform environment.
3) A sparger that introduces air into the medium through small holes.
4) Baffles that prevent vortexes and improve aeration.
5) Devices for controlling temperature, as fermentation generates or requires heat.
6) Sensors and controls for maintaining the optimal pH for microbial growth
This document discusses contamination and spoilage of milk and milk products. It describes how milk can become contaminated from sources like milking equipment and utensils. It also discusses the microorganisms involved in spoilage of raw milk, pasteurized milk, evaporated milk, condensed milk, sweetened condensed milk, and butter. Finally, it outlines several methods used to preserve milk and milk products, including aseptic practices, packaging, removal of microorganisms, use of heat through pasteurization and ultra-pasteurization, and use of low temperatures.
Fermentors are closed containers used for fermentation reactions. They come in two types - open and closed. Construction materials differ based on scale, with glass or stainless steel used for small scale and stainless steel, mild steel, wood, plastic or concrete for larger scales. Fermentors contain mechanically mixed impellers within a baffled cylindrical vessel to promote mixing and mass transfer. Key factors that must be controlled during fermentation include temperature, pH, dissolved oxygen, nutrient concentrations, mixing, and foam formation. Proper strain selection and sterilization of the fermentor are also important.
This document discusses xanthan gum, a biopolymer produced through the fermentation of glucose by the bacterium Xanthomonas campestris. It provides information on:
1) Xanthan gum's properties, structure, production process, and applications in foods, cosmetics, and industrial products like drilling fluids and textiles.
2) How xanthan gum is commercially produced through the fermentation of glucose in a bioreactor, followed by recovery processes to extract and purify the biopolymer.
3) Ongoing research seeking to improve xanthan gum production through genetic engineering of bacteria strains and the use of alternative carbon sources for fermentation.
The document discusses various methods for preserving microorganisms. Short term methods include periodic transfer to fresh medium, storage in saline suspension, and refrigeration. Long term methods involve storage under mineral oil, lyophilization (freeze drying), cryopreservation in liquid nitrogen, and storage in sterile soil or silica gel. Lyophilization works by freezing and then reducing moisture content through sublimation and desorption. It allows storage at room temperature for many years but can damage some microbes. Cryopreservation in liquid nitrogen at -196°C also enables long term storage of over 10-30 years without genetic change.
This document discusses biopreservation, which uses natural or controlled microorganisms and their antimicrobial compounds to extend the shelf life and improve the safety of foods. It describes various biopreservative agents like lactic acid bacteria, yeast, and bacteriophages and their modes of action in inhibiting pathogens. Specifically, it outlines classes of bacteriocins produced by lactic acid bacteria and their applications in preserving foods like meat, seafood, vegetables, and dairy products. The document also discusses regulatory requirements for using bacteriocins and the safety of lactic acid bacteria as biopreservatives.
Groups of Bacteria important in Food Bacteriology Saajida Sultaana
Lactic acid-forming bacteria, acetic acid-forming bacteria, and butyric acid-forming bacteria play important roles in food microbiology. Lactic acid-forming bacteria are involved in the production of sauerkraut, cheese, and wine spoilage. Acetic acid-forming bacteria oxidize ethanol to acetic acid and are used to make vinegar and can spoil alcoholic beverages. Butyric acid-forming bacteria, like Clostridium, are spore forming anaerobes.
Pure culture preservation of microbes are described in detain. Different short and long term preservation are explained in detail. Methods like Agar slant cultures (Sub culturing) & Refrigeration , Mineral Oil or Liquid Paraffin Method,Saline suspension storage, Drying in Vacuum, Storage at low temperatures (Cryopreservation) and Lyophilization (Freeze drying) are included.
This document discusses inoculum build up for industrial fermentation. It describes isolating microorganisms from nature, genetic modification to develop desirable strains, using mutation techniques to improve cultures, and preservation methods like lyophilization. Proper inoculum development is important - the culture must be active, healthy, and contamination-free in large volumes while retaining product formation abilities. Factors like medium composition and inoculum volume influence growth. Three common inoculum development programs are also mentioned. To obtain the full power point presentation, a payment of 20 USD or 400 RS can be sent to the provided bank account and email.
The document discusses various methods for producing and preserving starter cultures for fermented dairy products. It describes traditional liquid culture production methods and highlights that they are time-consuming and risk contamination. It then outlines several improvements to culture production including concentrated, freeze-dried cultures and cryoprotected frozen cultures that allow for direct inoculation and overcome issues with traditional methods. The document also discusses factors that affect survival of freeze-dried cultures and outlines three main systems for bulk starter culture production: using simple techniques; mechanically protected tanks; and propagation in a phage-inhibitory medium.
Microbial spoilage of fruits & vegetables9404577899
This document discusses microbial contamination and spoilage of fruits and vegetables. It outlines various methods of contamination during harvesting, transportation, handling, and processing. It also describes different preservation methods for vegetables and fruits, including aseptic techniques, heat, low temperatures, drying, and use of preservatives. Various types of microbial spoilage are outlined for both fresh and processed fruits and vegetables, caused by bacteria, molds, and fungi. The spoilage microorganisms and symptoms associated with each type of spoilage are listed.
Microbial contamination of pharmaceutical products can lead to spoilage or health hazards. Contamination can occur during manufacturing from water, the environment or packaging. It can be prevented through good manufacturing practices and controlling moisture, temperature, pH and packaging design. Spoilage results from microbial growth and causes product deterioration or infection. Factors influencing spoilage include the contaminant type/level, nutrients, moisture, temperature, pH and packaging. Strict control of these factors is needed to prevent issues.
Types of spoilage, factors affecting the microbial spoilage of pharmaceutical...Ms. Pooja Bhandare
PHARMACEUTICAL MICROBIOLOGY (BP303T)Unit-V Part-1
Types of spoilage, factors affecting the microbial spoilage of pharmaceutical products, source and type of contaminants. Introduction: Defintion Types of Microbial Spoilage:
1. Infection induced due to contaminated pharmaceutical products: Table no. 1.1 Common pathogens spoiling pharmaceutical products:
2. Physicochemical spoilage –
i) Viable growth ii) Gas production
iii) Colouration / Decolouration
iv) Odour formation
v) Taste change
3. Physical Spoilage:
Cracking of emulsion:
Odor changes
4. Biological spoilage:
Microbial Toxins
Microbial Metabolites
5. Chemical spoilage: Table 1.2 Susceptibility of pharmaceutical ingredients to microbial contamination
Factors affecting microbial spoilage
Size of contaminant inoculum
Nutritional factors
Moisture content
pH
Storage temperature
Redox potential
Packaging design
Sources and Types Of Contamination:
Personnel,
Poor facility design,
Incoming ventilation air,
Machinery and other equipment for production,
Raw material and semi-finished material,
Packaging material,
Utilities,
Different media used in the production process as well as for cleaning and Cleanroom clothing.
Preparation and quality control of immunological productsMayur D. Chauhan
The following presentation is only for quick reference. I would advise you to read the theoretical aspects of the respective topic and then use this presentation for your last minute revision. I hope it helps you..!!
Mayur D. Chauhan
Microbial Culture Preservation and its MethodsDENNISMMONDAH1
This document discusses various methods for preserving microbial cultures, including short term and long term methods. Short term methods include periodic transfer to fresh media, preservation using saline suspension, drying, and refrigeration. Long term methods discussed are preservation using liquid paraffin/mineral oil, glycerol, lyophilization (freeze drying), and cryopreservation in liquid nitrogen. The aim of preservation is to maintain cultures in viable condition for extended periods without genetic changes.
This document discusses sterilization of air and media. It defines sterilization as removing microorganisms through chemicals, heat, or radiation. For air sterilization, common methods are heating, radiation, chemicals, and filtration. Filtration uses depth or absolute filters to trap particles. Media sterilization can be in-situ or ex-situ. Common media sterilization methods are heat (such as autoclaving or steam), filtration, radiation (ionizing or non-ionizing), and chemicals (like ethylene oxide gas). Heat sterilization via autoclaving is most widely used.
The document discusses different types of bioreactors used in fermentation technology. It describes continuous stirred tank reactors, bubble column bioreactors, airlift bioreactors, fluidized bed bioreactors, packed bed bioreactors, photo-bioreactors, tower bioreactors, and rotary drum reactors. For each type of bioreactor, it provides details on the design, functioning, applications and advantages. Continuous stirred tank reactors provide good mixing but are open systems, while bubble column and airlift bioreactors rely on the bubbling of gas to promote mixing and circulation of the medium.
The document discusses foodborne infections and intoxications. Foodborne infections occur when harmful microorganisms in contaminated food grow in the intestines and cause illness, while intoxications result from toxins produced by microorganisms or present in plants/seafood. Common bacteria that can cause infections include Salmonella, Listeria, Campylobacter, and viruses like Hepatitis A and parasites such as Giardia. Symptoms include diarrhea and vomiting. Prevention methods include proper food handling and cooking practices.
Fermentation is a metabolic process where organic compounds like carbohydrates are broken down by microorganisms to release energy without oxygen. It is used to produce a variety of foods, beverages, industrial products, and more. There are several types of fermentation including alcoholic, lactic acid, propionic acid, and butyric acid fermentations. Fermentation can occur via solid state or submerged cultures in different types of bioreactors. Key factors that control microbial growth during fermentation include nutrients, pH, temperature, water activity, and presence of other microorganisms. Proper isolation techniques are required to culture pure microbial strains.
This document discusses important microorganisms in food microbiology, focusing on molds and yeasts. It describes the general characteristics, morphology, cultural characteristics, and physiological characteristics of molds and yeasts. Some molds and yeasts of industrial importance are also outlined, including Aspergillus, Penicillium, and Saccharomyces. The criteria used to classify and identify molds is also summarized.
This document discusses methods for isolating and cultivating animal and plant viruses. There are three main methods for animal viruses: embryonated chicken eggs, tissue cultures, and laboratory animals. Embryonated chicken eggs are commonly used as they provide several inoculation sites and are economical. Tissue cultures include primary cell cultures from animal tissues, diploid cell strains with normal chromosome numbers, and continuous cell lines with abnormal numbers that can undergo infinite divisions. Laboratory animals like primates and small mammals are also used but their use is now limited. For plant viruses, whole plants, plant tissue cultures, and protoplast cultures are used, with protoplasts being a standard technique. Insect cell cultures can also be used
This document defines fermentation and fermenter. It then describes the key components of a fermenter:
1) The vessel, which is designed to carry out fermentation under aseptic and controlled environmental conditions. Vessels come in small-scale laboratory or large-scale industrial sizes.
2) An impeller that provides mixing for oxygen transfer, heat transfer, and maintaining a uniform environment.
3) A sparger that introduces air into the medium through small holes.
4) Baffles that prevent vortexes and improve aeration.
5) Devices for controlling temperature, as fermentation generates or requires heat.
6) Sensors and controls for maintaining the optimal pH for microbial growth
This document discusses contamination and spoilage of milk and milk products. It describes how milk can become contaminated from sources like milking equipment and utensils. It also discusses the microorganisms involved in spoilage of raw milk, pasteurized milk, evaporated milk, condensed milk, sweetened condensed milk, and butter. Finally, it outlines several methods used to preserve milk and milk products, including aseptic practices, packaging, removal of microorganisms, use of heat through pasteurization and ultra-pasteurization, and use of low temperatures.
Fermentors are closed containers used for fermentation reactions. They come in two types - open and closed. Construction materials differ based on scale, with glass or stainless steel used for small scale and stainless steel, mild steel, wood, plastic or concrete for larger scales. Fermentors contain mechanically mixed impellers within a baffled cylindrical vessel to promote mixing and mass transfer. Key factors that must be controlled during fermentation include temperature, pH, dissolved oxygen, nutrient concentrations, mixing, and foam formation. Proper strain selection and sterilization of the fermentor are also important.
This document discusses xanthan gum, a biopolymer produced through the fermentation of glucose by the bacterium Xanthomonas campestris. It provides information on:
1) Xanthan gum's properties, structure, production process, and applications in foods, cosmetics, and industrial products like drilling fluids and textiles.
2) How xanthan gum is commercially produced through the fermentation of glucose in a bioreactor, followed by recovery processes to extract and purify the biopolymer.
3) Ongoing research seeking to improve xanthan gum production through genetic engineering of bacteria strains and the use of alternative carbon sources for fermentation.
The document discusses various methods for preserving microorganisms. Short term methods include periodic transfer to fresh medium, storage in saline suspension, and refrigeration. Long term methods involve storage under mineral oil, lyophilization (freeze drying), cryopreservation in liquid nitrogen, and storage in sterile soil or silica gel. Lyophilization works by freezing and then reducing moisture content through sublimation and desorption. It allows storage at room temperature for many years but can damage some microbes. Cryopreservation in liquid nitrogen at -196°C also enables long term storage of over 10-30 years without genetic change.
This document discusses biopreservation, which uses natural or controlled microorganisms and their antimicrobial compounds to extend the shelf life and improve the safety of foods. It describes various biopreservative agents like lactic acid bacteria, yeast, and bacteriophages and their modes of action in inhibiting pathogens. Specifically, it outlines classes of bacteriocins produced by lactic acid bacteria and their applications in preserving foods like meat, seafood, vegetables, and dairy products. The document also discusses regulatory requirements for using bacteriocins and the safety of lactic acid bacteria as biopreservatives.
Groups of Bacteria important in Food Bacteriology Saajida Sultaana
Lactic acid-forming bacteria, acetic acid-forming bacteria, and butyric acid-forming bacteria play important roles in food microbiology. Lactic acid-forming bacteria are involved in the production of sauerkraut, cheese, and wine spoilage. Acetic acid-forming bacteria oxidize ethanol to acetic acid and are used to make vinegar and can spoil alcoholic beverages. Butyric acid-forming bacteria, like Clostridium, are spore forming anaerobes.
Pure culture preservation of microbes are described in detain. Different short and long term preservation are explained in detail. Methods like Agar slant cultures (Sub culturing) & Refrigeration , Mineral Oil or Liquid Paraffin Method,Saline suspension storage, Drying in Vacuum, Storage at low temperatures (Cryopreservation) and Lyophilization (Freeze drying) are included.
This document discusses inoculum build up for industrial fermentation. It describes isolating microorganisms from nature, genetic modification to develop desirable strains, using mutation techniques to improve cultures, and preservation methods like lyophilization. Proper inoculum development is important - the culture must be active, healthy, and contamination-free in large volumes while retaining product formation abilities. Factors like medium composition and inoculum volume influence growth. Three common inoculum development programs are also mentioned. To obtain the full power point presentation, a payment of 20 USD or 400 RS can be sent to the provided bank account and email.
The document discusses various methods for producing and preserving starter cultures for fermented dairy products. It describes traditional liquid culture production methods and highlights that they are time-consuming and risk contamination. It then outlines several improvements to culture production including concentrated, freeze-dried cultures and cryoprotected frozen cultures that allow for direct inoculation and overcome issues with traditional methods. The document also discusses factors that affect survival of freeze-dried cultures and outlines three main systems for bulk starter culture production: using simple techniques; mechanically protected tanks; and propagation in a phage-inhibitory medium.
Microbial spoilage of fruits & vegetables9404577899
This document discusses microbial contamination and spoilage of fruits and vegetables. It outlines various methods of contamination during harvesting, transportation, handling, and processing. It also describes different preservation methods for vegetables and fruits, including aseptic techniques, heat, low temperatures, drying, and use of preservatives. Various types of microbial spoilage are outlined for both fresh and processed fruits and vegetables, caused by bacteria, molds, and fungi. The spoilage microorganisms and symptoms associated with each type of spoilage are listed.
Microbial contamination of pharmaceutical products can lead to spoilage or health hazards. Contamination can occur during manufacturing from water, the environment or packaging. It can be prevented through good manufacturing practices and controlling moisture, temperature, pH and packaging design. Spoilage results from microbial growth and causes product deterioration or infection. Factors influencing spoilage include the contaminant type/level, nutrients, moisture, temperature, pH and packaging. Strict control of these factors is needed to prevent issues.
Types of spoilage, factors affecting the microbial spoilage of pharmaceutical...Ms. Pooja Bhandare
PHARMACEUTICAL MICROBIOLOGY (BP303T)Unit-V Part-1
Types of spoilage, factors affecting the microbial spoilage of pharmaceutical products, source and type of contaminants. Introduction: Defintion Types of Microbial Spoilage:
1. Infection induced due to contaminated pharmaceutical products: Table no. 1.1 Common pathogens spoiling pharmaceutical products:
2. Physicochemical spoilage –
i) Viable growth ii) Gas production
iii) Colouration / Decolouration
iv) Odour formation
v) Taste change
3. Physical Spoilage:
Cracking of emulsion:
Odor changes
4. Biological spoilage:
Microbial Toxins
Microbial Metabolites
5. Chemical spoilage: Table 1.2 Susceptibility of pharmaceutical ingredients to microbial contamination
Factors affecting microbial spoilage
Size of contaminant inoculum
Nutritional factors
Moisture content
pH
Storage temperature
Redox potential
Packaging design
Sources and Types Of Contamination:
Personnel,
Poor facility design,
Incoming ventilation air,
Machinery and other equipment for production,
Raw material and semi-finished material,
Packaging material,
Utilities,
Different media used in the production process as well as for cleaning and Cleanroom clothing.
Microbial spoilage-by S.D.Mankar types, sources of contamination, factors,Ass...someshwar mankar
Types of spoilage, factors affecting the microbial spoilage of pharmaceutical products,
sources and types of microbial contaminants, assessment of microbial contamination and
spoilage.
This document discusses various methods for preserving pure microbial cultures, including short-term and long-term methods. Short-term methods include periodic transfer to fresh media, storage in paraffin or mineral oil, preservation using glycerol, and storage through drying or refrigeration. Long-term methods allow for extended preservation and involve oil storage, saline suspension, immersion in water, storage in soil, lyophilization, or cryopreservation through freezing in liquid nitrogen. Whichever preservation technique is used, it is important to routinely check the quality of preserved microbial stocks to ensure their viability and characteristics remain unchanged over long periods of storage.
Starter cultures are microorganisms used to initiate fermentation processes and produce desirable qualities in fermented foods. They are selected based on their ability to produce acids that preserve foods while inhibiting spoilage. Factors like antibiotics, bacteriophages, residual detergents and disinfectants can inhibit starter cultures and negatively impact food quality. Proper selection and handling of starter cultures is important for producing foods with consistent quality through controlled fermentation.
This document provides an overview of various food preservation methods for short and long shelf life foods. It discusses techniques such as heating, cooling, drying, adding natural preservatives like salt or sugar, and using chemical preservatives. It explains how each method works to control microorganisms, deactivate enzymes, and prevent spoilage reactions. Specific methods like drying, acidification, sugar/salt addition, and smoke exposure are then described in more detail regarding their mechanisms and considerations.
Class 12,chemistry project by Prekshya Dhakal.docxAnitaPoudel5
This document discusses a study on different types of food preservatives used in foods. It begins by introducing food preservatives and their purpose of preventing spoilage. It then describes the history of preservatives and categorizes them into three types: natural, chemical, and artificial. For each type, several common examples are provided and briefly explained. The roles of preservatives in food are maintaining quality, improving nutrition, and delaying spoilage. Both benefits and potential side effects of preservatives are mentioned. The document concludes that while preservatives ensure food safety, artificial preservatives can have negative health impacts.
Chemical preservatives for semisolids must be carefully evaluated for their stability with regard to the other components of the formulation as well as to the container. Plastic containers may absorb the preservative and thereby decrease the quantity available for inhibiting or destroying the microorganism’s responsible for spoilage. Some preservatives may sting or irritate the mucous tissues of the eye or nasal passages. Methylparabens and propylparabens tend to be more irritating when applied in the nose than quaternary ammonium compounds or the phenylmercuric salts. Boric acid may be used in the ophthalmic preparations, but is omitted from products to be used in the nose because of possible toxic effects if absorbed in large quantities.
Water activity and types of food based on water activitySaptadeep Sanyal
Water activity is a measure of available water in a food and is important because it determines microbial growth. It is defined as the ratio of vapor pressure of water in a food to vapor pressure of pure water at the same temperature. Foods with water activities below 0.6 inhibit mold growth, increasing shelf life. Controlling water activity through addition of solutes like salt or sugar allows some foods to be stored without refrigeration as intermediate moisture foods.
Prof.Mr.Kiran K. Shinde (M.Pharm), Assistant professor (VNIPRC)
Pharmaceutical microbiology (Second year b.pharm) (3rd semester)
Introduction
Types of Spoilage
Factors affecting the Microbial spoilage of pharmaceutical products
Sources and Types of Contamination
Assessment of microbial contamination and spoilage
This document discusses intermediate moisture foods (IMF), which are foods with a water activity between 0.6-0.9 that prevents microbial growth. Examples include jams, jellies, candies, baked goods, honey, and dried meats. IMF have 10-50% moisture. Water activity measures the availability of water for microbial growth. IMF provide food preservation by controlling water activity and may include additional preservatives. While IMF don't require refrigeration, they can contain high sugar or salt and their texture may deteriorate if not properly handled.
Hydra Bio Blocks for Grease Trap Bacteria TreatmentAmyWhite11
Hydra offers bacteria blocks for effluent treatment in grease trap and also to remove false odours & FOG deposits. Bio Block dissolves slowly and lasts up to 6 to 8 weeks.
Visit here: http://grease-eater.co.uk/grease-trap-bacteria-blocks.html
This document provides an overview of freeze drying. It discusses that freeze drying involves freezing food, then removing almost all moisture in a vacuum chamber to preserve the food. It also discusses that freeze drying was originally developed to preserve blood plasma during World War II. Finally, it provides details on the freeze drying process, materials used, types of freezing, advantages and disadvantages of freeze drying.
Hurdle technology in Fish PreservationShubham Soni
Hurdle Technology is a kind of combination of Mechanisms to preserve the perishable commodity like Fish and the Fish Products, its even useful in other Industries like Poultry, Agri-Industries etc.
Just Keep Creating Hurdles for Microbes and we all we have a healthy and Hygienic Life...!
This document discusses the quantitative analysis of viable bacteria and fungi in liquid preparations. It analyzed 12 samples of liquid antacid suspension. 3 samples exceeded the USP limit for aerobic bacterial count, ranging from 0-1000 CFU per mL. 6 samples contained fungi and 8 contained bacteria. Specific bacteria identified included E. coli in 2 samples, Salmonella in 1 sample, and Staphylococcus aureus in 5 samples. The document provides background on types of bacteria that may contaminate liquids, including Salmonella and its identification. Proper sealing of containers is important from a microbiological perspective.
All information regarding which factors involve in food for growth of microorganisms.
Introduction, Food as a substrate for microorganism
a. pH, aw, O-R potential
b. Nutrient Content
c. Accessory food substances
d. Inhibitory substances & biological structure
e. Combined effects of factors affecting growth
Interactions between microorganisms and our foods are sometimes beneficial.
The interactions between microorganisms, plants, and animals are natural and constant.
The ecological role of microorganisms and their importance in all the geochemical cycles in nature.
In most cases microorganisms use our food supply as a source of nutrients for their own growth. This, of course, can result in deterioration of the food. By increasing their numbers, utilizing nutrients, producing enzymatic changes, and contributing off-flavors by means of breakdown of a product or synthesis of new compounds they can “spoil” a food.
This is a normal consequence of the action of microorganisms, since one of their functions in nature is to convert reduced forms of carbon, nitrogen, and sulfur in dead plants and animals to the oxidized form required by plants, which in turn are consumed by animals.
So by simply “doing their thing” in nature they frequently can render our food supply unfit for consumption. To prevent this we minimize the contact between microorganisms and our foods (prevent contamination) and also eliminate microorganisms from our foods, or at least adjust conditions of storage to prevent their growth (preservation).
1. Culture media are nutrient materials prepared for the growth of microorganisms in the laboratory. Different microbes require different nutrients and conditions in the culture media.
2. Agar is commonly added to culture media to solidify it for growing bacteria on solid surfaces like Petri dishes and slants. Agar solidifies the media without degrading.
3. Pure cultures of microbes are necessary for most bacteriological work and are obtained using methods like streak plating that isolate single colonies from mixed cultures.
Proteins and peptides have received increased interest in the current drug therapies
Recently, approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, exposure to infectious agents, autoimmunity/ inflammation and genetic disorders.
Their high potency and selectivity.
Their low accumulation in tissues.
They have potentially lower toxicity than the small drug molecules.
Provide abroad range of targets, which could represent a basis for personalized medication.
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Microbial spoilage, infection risk and.pptx
1.
2. • Types and Size of Contaminant Inoculum
- Before doing a formula, the formulator should consider the
environment and usage to which the product is likely to be
subjected during its life and the history of similar
medicines, why?
to build as much protection as possible against non-standard
encounters, such as additional preservation for a syrup if
osmotolerant yeast contamination is particularly likely
- If microbial failure occurs, identification of the
contaminant(s) & knowledge of microbial ecology are
very useful in tracking down the defective steps in the
design or production process
3. Types and Size of Contaminant Inoculum
- Very low levels of contaminants which are unable to replicate in a
product might not cause appreciable spoilage but, if a surge in
contaminant bio-burden occur, the built-in protection could
be insufficient and spoilage occurs
- This surge might arise if:
1. Raw materials were unusually contaminated;
2. A problem of the plant-cleaning protocol occurred;
3. Biofilm detached itself from within supplying pipework;
4. There was demolition or maintenance work in the vicinity of the
manufacturing site
5. Gross misuse of the product during administration
4. Types and Size of Contaminant Inoculum
- Inoculum size alone is not always a reliable indicator of spoilage
potential. e.g. a very low level of, aggressive Pseudomonads in a
weakly preserved solution may suggest a greater risk than tablets
containing fairly high numbers of fungal and bacterial spores.
When an aggressive contaminant enters a medicine, there may be an
appreciable lag period before significant spoilage begins, the
duration of which decreases disproportionately with increasing
contaminant loading. However, since there is usually a long delay
between manufacture and administration of factory-made
medicines, growth and attack could start during this period unless
additional steps are taken to prevent it.
5. Types and Size of Contaminant Inoculum
- The isolation of a particular m.o. from spoiled
product does not necessarily mean that it was the
initiator of the attack. It could be a secondary
opportunistic contaminant which had overgrown
the primary spoilage organism once the
physicochemical properties had been favourably
modified by primary spoiler.
6. Nutritional Factors
- Many common spoilage microorganisms have simple nutritional
requirements and metabolic adaptability This enables them to
utilize many of the components of medicines as substrates for
biosynthesis and growth, even including trace materials
contained in them.
Even demineralized water prepared by good ion-exchange methods
normally contains sufficient nutrients to allow significant
growth of many water-borne Gram-negative bacteria such as
Pseudomonas spp.
That’s why when such contaminants fail to grow in a medicine
it is unlikely to be as a result of nutrient limitation but due to
other, non-supportive, physicochemical or toxic properties.
7. Nutritional Factors
- Most acute pathogens require specific growth factors
normally associated with the tissues they infect but
which are often absent in pharmaceutical formulations.
Therefore, they will unlikely multiply in them, but they
may remain viable and infective for an appreciable time
in some dry products where the conditions are
protective.
- The use of crude vegetable or animal products in a
formulation provides an additionally nutritious
environment.
8. Moisture Content: Water Activity (Aw)
- Microorganisms require readily accessible water in appreciable
quantities for growth.
- Although some solute-rich medicines such as syrups appear to be
'wet', microbial growth in them may be difficult, why?
Since the microbes have to compete for water molecules with the
large numbers of sugar and other molecules of the formulation
which also interact with water via hydrogen bonding.
- An estimate of the proportion of the unbound water in a
formulation available to equilibrate with any microbial
contaminants and facilitate growth can be obtained by
measuring its water activity (Aw).
AW = vapour pressure of formulation / vapour pressure of water
…(under similar conditions )
10. Moisture Content: Water Activity (Aw), examples:
NaCl Solutions:
The scale is different for the %’s of different solutes
- The greater the (same) solute concentration, the lower is the
water activity
11. Moisture Content: Water Activity (Aw)
- With the exception of halophilic bacteria, most m.o
grow best in dilute solutions (high Aw) and, as solute
conc. rises (lower Aw), growth rates decline
until a minimal, growth-inhibitory Aw is reached.
- Limiting Aw values are of the order of :
Gram-negative rods: 0.95
Staphylococci, Micrococci and Lactobacilli: 0.9
Most yeasts: 0.88
12. Moisture Content: Water Activity (Aw)
- The Aw of aqueous formulations can be lowered to increase resistance to
microbial attack by the addition of high concentrations of sugars or
polyethylene glycols.
- Since there are trends to eliminate sucrose from medicines, alternative
solutes are used, such as sorbitol and fructose, which are not thought
to encourage dental caries.
- But, syrup-fermenting osmo-tolerant yeasts were found to spoil
products with Aw levels as low as 0.73, while some filamentous fungi can
grow at even lower values, such as Aspergillus glaucus (0.61)
That’s why even Syrup BP (67% sucrose; Aw= 0.86) has been reported to
occasionally fail to inhibit osmo-tolerant yeasts and hence additional
preservation may be necessary
13. Moisture Content: Water Activity (Aw)
- Aw can also be reduced by drying, although the dry, often
hygroscopic, medicines (tablets, capsules, powders) will
require suitable packaging to prevent reabsorption of
water and consequent microbial growth.
- Some tablet film coatings are now available which
greatly reduce water vapour uptake during storage.
These might contribute to increased microbial stability
during storage in particularly humid climates,
although suitable foil strip packing may be more effective,
but also more expensive.
14. Moisture Content: Water Activity (Aw)
- Without proper packaging, condensed water films can
accumulate on the surface of 'dry’ products such as
tablets or bulk oils following storage in damp
atmospheres with fluctuating temperatures, resulting
in high localized Aw which can initiate fungal growth.
- Dilute aqueous films similarly formed on the surface
of viscous products such as syrups and creams, or
exuded by syneresis from hydrogels, reach sufficiently
high Aw to permit surface yeast and fungal spoilage.
15. Redox Potential
- The ability of microbes to grow in an environment
is influenced by its oxidation-reduction balance
(redox potential) since they require compatible
terminal electron acceptors to permit function of their
respiratory pathways.
- The redox potential even in fairly viscous emulsion
may be quite high due to the high solubility of oxygen
in most fats & oils.
16. Storage Temperature
- Spoilage of pharmaceuticals could occur over the range of about -20°
to 60°C, although much less likely at the extremes.
- The actual storage temperature may determine the spoilage by
particular types of microorganisms.
- Storage in a deep freeze at -20°C or lower is used for long term
storage of foodstuffs and some pharmaceutical raw materials.
- Dispensed total parenteral nutrition (TPN) feeds have also been stored in
hospitals for short periods at -20°C to even further minimize the risk
of growth of any contaminants which might have been introduced
during their aseptic compounding.
17. Storage Temperature
- Reconstituted suspensions and multi-dose eye drop packs
are sometimes dispensed with the instruction to 'store in
a cool place' such as a domestic fridge (2°-8°C), partly to
reduce the risk of in-use contamination.
- On the other hand, ‘Water for Injections’ is usually
held at 80°C or above after distillation (prior to
packing and sterilization) to prevent possible regrowth of
Gram-negative bacteria, and the release of endotoxins
18. pH
- Extremes of pH prevent microbial attack.
- Around neutrality bacterial spoilage is more likely, with reports of
Pseudomonads and related Gram-negative bacteria growing in
antacid mixtures, flavoured mouth washes and in distilled or
demineralized water.
- Above pH 8, e.g. with soap-based emulsions, spoilage is rare.
- For products with low pH levels such as the fruit juice-flavoured
syrups ( pH 3-4) mould or yeast attack is more likely. Yeasts can
metabolize organic acids and raise the pH to levels where
secondary bacterial growth can occur.
- In food industry low pH adjustment can be made to preserve
foodstuffs (pickling, yoghurt), but this is not practical for medicines (
why??? ).
19. Packaging Design
- Packaging should be made in a way to control the
entry of contaminants during both storage and
use.
- The most important dosage form to be protected
are the parenteral drugs because of the high risks
of infection by this route.
- Self-sealing rubber closures must be used to
prevent microbial entry into multi-dose injection
containers following drug withdrawals
20. Packaging Design
- Wide-mouthed cream jars will allow the entry of fingers
with their high bioburden of contamination.
Thus, it is better to replace them with narrow nozzle and
flexible screw capped tubes.
- For medicines which rely on their low Aw to prevent
spoilage, packaging such as strip foils must be of water
vapour-proof materials with fully efficient seals.
- Cardboard outer packaging and labels themselves can
become substrates for microbial attack under humid
conditions; therefore preservatives are often included to
reduce their risk of damage.
21. Protection of m.o. within Pharmaceutical Products
- The survival of microorganisms in particular environments is
influenced by the presence of various relatively inert materials.
- - Microbes can be more resistant to heat or desiccation in the presence
of some polymers such as starch, acacia or gelatin.
- Adsorption onto naturally occurring particulate material
may aid establishment and survival in some environments.
- The presence of some surfactants, suspending agents and proteins can
increase the resistance of microorganisms to preservatives, over and
above their direct inactivating effect on the preservative itself.
22. Contaminated pharmaceutical products may present
a potential health hazard to the patient.
• Contamination with pathogenic bacteria (e.g.
Salmonella spp) forms a special risk since they can
cause infections in a wide range of patients.
• The presence of opportunists with limited
pathogenicity also present significant challenge to
compromised patients.
23. The outcome of using contaminated products vary from
patient to patient depending on the type & degree of
contamination & how the product to be used.
- The most serious effects are expected to be with
contaminated injections as generalized bacteraemic shock
& sometimes death is reported.
- Wound or sore in broken skin may become locally infected
which may extend the hospital bed occupancy.
• Most medicament related infections are difficult to be
recognized by health practitioners which causes the spread of
infection over several months
24. :Gram -negative bacteria
- G- negative bacteria were responsible for numerous outbreaks.
- Pseudomonas spp have simple nutritional requirements &
multiply significantly in aqueous products
Cornea when scratched or damaged by irritant chemicals offers
little resistance to Pseudomonas and hence contaminated ophthalmic
solutions have resulted in frequent cases of infections; some leading to
loss of sight.
Pseudomonas contaminating antiseptic solutions caused skin
infections in burnt patients resulting in failure of skin grafts &
death.
Infections of eczematous skin & respiratory infections in neonates
were caused by contaminated ointments & creams.
25. :Gram -negative bacteria
-Infections by Salmonella spp were reported & the m.o.
was isolated from products contaminated with it
(tablets, pancreatin, thyroid extracts).
- Oral mixtures & antacid suspensions can support the
growth of Gram -negative bacteria & resulted in
serious effects in immunocompromised patients (e.g.
as a result of antineoplastic chemotherapy)
- Bladder wash out solutions contaminated with
Gram - negative bacteria caused painful infections
26. Microbial toxins:
- G-negative bacteria contain endotoxins (LPS) which can
remain active in products even after cell death & some
can survive moist heat sterilization
- Endotoxins are inactive via oral route but if they enter
blood stream via contaminated infusion fluids (even
in ng level) or via diffusion across membranes from
contaminated haemodialysis solution they can induce
serious physiological effects.
- Endotoxins cause fever, activation of the cytokine system,
endothelial cell damage & these all lead to septic & often
febrile shock.
27. Clinical rxns may range from local infections of wounds or
broken skin (contaminated topical prep) to GI infections
(contaminated oral products) to serious widespread
infections such as bacteraemia or septicemia possibly
resulting in death (contaminated infusion)
• Clinical rxns resulting from the use of contaminated
medicament may be evident in one patient but not in
another one depending on many factors, among which are:
1. Type & Degree of Microbial Contamination
2. Route of Administration
3. Resistance of the Patient to Microbial Infections
28. 1. Type & Degree of Microbial Contamination
- Microorganisms contaminating medicaments are classified
into true pathogens or opportunistic pathogens.
- Pathogens rarely occur in products but if present they
cause serious problems, examples:
Clostridium tetani: caused wound infections & cases of
neonatal death resulted from use of contaminated talcum
Powder
Salmonella spp: caused outbreaks of salmonellosis due
to ingestion of contaminated thyroid & pancreatic
powders
29. 1. Type & Degree of Microbial Contamination
- Opportunists like P. aeruginosa, Klebsiella spp. And Serratia spp
are more frequently isolated from medicinal products.
The main concern with these organism is that their simple
nutritional requirements enable them to survive in a wide
range of pharmaceuticals, thus they present in high numbres
106-107 CFU/g or ml, although the product itself may not show
visible sign of contamination.
Compromised patients are considered at risk from infection
with these m.o.
- The critical dose of m.o that will initiate an infection is unknown
& varies between spp & within spp.
30. 2. Route of Administration
- Ophthalmic & parenteral route:
Contaminated products injected directly into blood stream or instilled into the
eye cause the most serious problems.
Injectable & ophthalmic solutions are often simple & provide sufficient nutrient
for G-ve opportunists.
If contaminated; the product may end up with a bioburden as high as 106 CFU/ml
in addition to the potential production of endotoxins
Total parenteral nutrition fluids provide even more nutritional support for
contaminants
Intrathecal & epidural injections are potentially hazardous procedures, and thus
in practice they are given through bacterial filters.
P. aeruginosa (contaminant of eye drops) has caused serious ophthalmic
infections, including loss of sight. The problem is compounded when the eye
is damaged by improper use of contact lenses or scratched by fingernails or
cosmetic applicators.
31. 2. Route of Administration
- Contaminated orally ingested products have different fate.
This depends on whether the drug was taken on full or
empty stomach as stomach acidity provides a barrier.
- Contaminants in topical products may cause little harm if
applied on intact skin, why?
because intact skin provides a mechanical barrier &
normal flora competes with the few contaminants.
however, damaged skin (sores, burns, surgery, wounds)
may be rapidly colonized & infected by opportunists
potentially causing serious problems
32. 3. Resistance of the Patient to Microbial Infections
- Very important in determining the outcome of a medicament borne
infection
- Hospitalized patients are more exposed and susceptible to
infection than those treated in the general community
- Neonates, the elderly, diabetics and traumatized patients (by
surgery, accidents…) are at special risk because they may have
impaired defence mechanisms
- Immunocompromised people (patients with leukaemia, HIV
or treated with immunosuppressants) are most prone to infections.
That’s why it is better to provide them with all medicines in a
sterile form!
33. Therapeutic agents
Through spoilage, active drug constituents may be
metabolized to less potent or chemically inactive forms.
Under laboratory conditions, it has been shown that a variety
of microorganisms can metabolize a wide assortment of
drugs, resulting in loss of activity. Materials as diverse
as alkaloids (morphine, strychnine, atropine), analgesics
(aspirin, paracetamol), thalidomide, barbiturates, steroid
esters and mandelic acid can be metabolized and serve as
substrates for growth.
34. metabolism of atropine in eye drops by
contaminating fungi
inactivation of penicillin injections by b-lactamase-
producing bacteria
steroid metabolism in damp tablets and creams by
fungi; microbial
hydrolysis of aspirin in suspension by esterase
producing bacteria
chloramphenicol deactivation in an oral medicine by
a chloramphenicol acetylase-producing contaminant.
35. Surface-active agents
Alkyl and alkylbenzene sulphonates and sulphate esters are
metabolized by oxidation of their terminal methyl groups
followed by sequential oxidation of the alkyl chains and
fission of the aromatic rings.
Generally, ease of degradation decreases with increasing
chain length and complexity of branching of the alkyl chain.
Non-ionic surfactants, such as alkylpolyoxyethylene
alcohol emulsifiers, are readily metabolized by a wide variety
of microorganisms.
36. Ampholytic surfactants, based on phosphatides, betaines and
alkylaminosubstituted amino acids, are an increasingly
important group of surfactants and are generally reported
to be reasonably biodegradable.
The cationic surfactants used as antiseptics and preservatives
in pharmaceutical applications are usually only slowly degraded
at high dilution in sewage.
Pseudomonads have been found growing readily in quaternary
ammonium antiseptic solutions, largely at the expense of other
ingredients such as buffering materials, although some
metabolism of the surfactant has also been observed.
37. Organic polymers
thickening and suspending agents
microbial depolymerization, specific classes of extracellular
enzymes, nutritive fragments and monomers.
amylases (starches), pectinases (pectins), cellulases
(carboxymethylcelluloses, but not alkylcelluloses), uronidases
(polyuronides such as in tragacanth and acacia), dextranases
(dextrans) and proteases (proteins).
Fats and oils
Fungal attack, condensed moisture films on the surface of oils
in bulk, or where water droplets have contaminated the bulk
oil phase.
38. Sweetening, flavouring and colouring agents
colouring agents (such as tartrazine and amaranth) and
flavouring agents (such as peppermint water) Pseudomonas
spp., including Ps. Aeruginosa.
39. Preservatives and disinfectants
preservatives and disinfectants, metabolized ,Gram-
negative bacteria, concentrations below their
effective ‘use’ levels. Growth of pseudomonads in
stock solutions of quaternary ammonium antiseptics
and chlorhexidine has resulted in infection of
patients.
Pseudomonas spp. have metabolized 4-
hydroxybenzoate ester preservatives contained in
eye-drops and caused serious eye infections, and
have also metabolized the preservatives in oral
suspensions and solutions.
40. Early indications of spoilage are often organoleptic,
‘sour’ fatty acids, ‘fishy’ amines, ‘bad eggs’, bitter, ‘earthy’ or sickly
tastes and smells.
discolouration by microbial pigments of various shades.
Thickening and suspending agents such as tragacanth, acacia or
carboxymethylcellulose , depolymerization, loss of viscosity, and
sedimentation.
microbial polymerization of sugars and surfactant, slimy, viscous
masses in syrups, shampoos and creams.
fungal growth in creams, ‘gritty’ textures.
Changes in product pH, secondary attack by microbes previously
inhibited by the initial product pH.
Gaseous metabolites may be seen as trapped bubbles
within viscous formulations.
41. Metabolism of surfactants, reduce stability,
‘creaming’ of the oil globules in emulsions.
Lipolytic release of fatty acids from oils will
lower pH and encourage coalescence of oil
globules and ‘cracking’ of the emulsion. Fatty
acids and their ketonic oxidation products, sour
taste and unpleasant smell, bubbles of gaseous
metabolites may be visible, trapped in the
product, and pigments may discolour it
42. Why to add a preservative:
1. To kill any anticipated low levels of contaminants,
where from?
a. Remaining in a non-sterile medicine after
manufacturing
b. Entering during storage
c. Introduced during usage especially the repeated
withdrawal of doses from a multi-dose container
2. To further reduce the risk of spoilage
43. If a medicine is unlikely to encourage growth or
survival of contaminants and the infective risk is
low, then a preservative might be
unnecessary
- Examples: tablets, capsules and dry powders
• Preservatives should not be added to deal with
failures in poorly controlled manufacturing
processes
44. Properties of an ideal properties:
- Broad spectrum and rapid activity
to rapidly kill all microbial contaminants as they
enter the medicine
- Non-irritant and non-toxic to the patient
- Selective in reacting with contaminants and not
the formulation ingredients
- Stable and effective throughout the life of the
product
45. But:
- The most active antimicrobial agents are generally non-
selective
- The remaining preservatives have only modest antimicrobial
efficacy
- There are no preservatives considered sufficiently non-toxic for
use in highly sensitive areas such as CNS and within the eye
- Rapid killing of all contaminants may only be possible for
relatively simple aqueous solutions, whereas for
physicochemically complex systems only inhibition of growth
and slow rate of killing may be realistically achieved.
46. Effect of preservative concentration, temperature and size of inoculum:
- Changes in the efficacy of preservatives vary exponentially with changes in
concentration depending on the type of preservative Remember the
concentration exponent (η)!
- Changes in product temperature will alter efficacy in proportions, related to
different types of preservative Q10!
- If concurrent change in temp & conc → more complex scenario
Example: if a 0.1% chlorocresol (η = 6, Q10 = 5) solution completely killed a
suspension of E. coli at 30°C in 10 minutes, it would require around 90 minutes to
achieve a similar effect if the temperature was lowered to 20°C and slight overheating
during production had resulted in a 10% loss by vaporization in the chlorocresol
concentration (other factors remaining constant)
47. Effect of preservative concentration, temperature and size of
inoculum:
- Preservative molecules are used up as they inactivate microorganisms
and as they interact non-specifically with the significant quantities of
contaminant 'dirt‘ introduced during use.
This will result in a progressive and exponential decline in the efficiency
of the remaining preservative.
- Preservative 'capacity' :
- describes the cumulative level of contamination that a preserved
formulation can cope with before the preservative becomes
ineffective.
This will vary with preservative type and complexity of the formulation.
48. Most preservatives interact in solution with ingredients of pharmaceutical
formulations to varying extents via a number of weak bonding
attractions as well as with any microorganisms present.
- This can result in unstable equilibrium in which only a small proportion
of the total preservative present is 'available' to inactivate m.o., and the
resultant rate of killing may be less than anticipated from the
performance of simple aqueous solutions.
- However, the 'unavailable' preservative may still, contribute to the
irritancy of the product.
• When solute concentrations are very high and Aw is appreciably
reduced, the efficiency of preservatives is often reduced and may
be even inactive at very low Aw.
- That’s why it is pointless to include preservatives in very low Aw
products such as tablets and capsules.
49. 1. Effect of product pH
- In the weakly acidic preservatives, the unionized molecules are the active
ones & they have significant efficacy at pHs where ionization is low.
- -Benzoic and sorbic acids (pKa = 4.2 and 4.75, respectively) have limited
preservative usefulness above pH 5.
-4(p)-hydroxybenzoate esters with their non-ionizable ester group and poorly
ionizable hydroxyl substituent (pKa ca. 8.5) have moderate protective effect
even at neutral pH levels.
-The activity of quaternary ammonium preservatives and chlorhexidine
resides with their cations and are effective in products of neutral pH.
- Formulation pH can also directly influence the sensitivity of microorganisms
to preservatives
50. 2. Efficiency in multiphase systems
- In a multiphase formulation, such as an oil-in-water emulsion,
preservative molecules distribute themselves in an unstable
equilibrium between the bulk aqueous phase and
the oil phase by partition
the surfactant micelles by solubilisation
polymeric suspending agents and other solutes by competitive
displacement of water of solvation
particulate and container surfaces by adsorption
any microorganisms present
51. 2. Efficiency in multiphase systems
- Generally, the overall preservative efficiency can be related
to the small proportion of preservative molecules
remaining unbound in the bulk aqueous phase.
Although as this becomes depleted some slow re-equilibration between
the components can be anticipated.
- The loss of neutral molecules into oil and micellar phases
may be favoured over ionized species, although
considerable variation in distribution is found between
different systems.
52. 3. Effect of container or packaging
- Preservative availability may be reduced by interaction with
packaging materials.
- Examples:
The permeation of phenolic preservatives into the rubber
closure of multi-dose injection or eye-drop containers and
their interaction with flexible nylon tubes for creams.
Quaternary ammonium preservative levels in formulations
have been significantly reduced by adsorption onto the
surfaces of plastic and glass containers.
Volatile preservatives such as chloroform are lost by the
routine opening and closing of containers
53. QA forms a scheme of management which includes
all the procedures necessary to provide a high
probability that a medicine will conform consistently
to a specified description of quality.
It includes
- formulation design & development (R&D)
- good pharmaceutical manufacturing practice
(GPMP)
- quality control QC
- post marketing surveillance
54. Risk assessment for each product should be made
starting from raw materials, to administration.
- Risk assessments are complicated due to uncertainties
about the exact contaminant & spoilage expected.
- Usually the manufacturers make the worst-case scenario &
design strategies to cover it fully, so that lesser problems
are also included.
• Also, it must be assumed that people administering the
medicament are not highly skilled & aware of
contamination control so that additional detailed
information on administration & even training must be
provided.
55. The best way to eliminate the risk of contamination & spoilage is
by sterilization, but!
- it incurs high cost so sterile products are kept to be used for
situations
were there is high risk of consequent infection from contamination.
• In parenteral products, high risk of infection by contamination &
presence of concerns of systemic toxicity of preservatives
resulted in the production of sterile single-dosage units.
• However, with eye-drops the risk is lesser & sterile multidose
products with preservatives to protect against inuse contamination
is accepted.
• Sterile single-dose units are more common in hospitals where
there is increased risk of infection.
56. Oral & topical routes of admin present low risks of infection & the
emphasis is on the control of microbial content during
manufacturing & subsequent protection of the formulation from
spoilage.
• In the design process it is necessary to include features in the
formulation & delivery system that provide protection against
contamination because preservative use should be only
considered when there is clear benefit due to toxicity & irritancy
problems.
• Among these features:
- Manipulation of physicochemical properties like Aw
- Elimination of certain ingredient
- Selection of container & preservative individually & collectively
contribute to the stability of the product.
57. Laboratory tests (preservative effectiveness tests) were designed to challenge the
product with artificial bioburden. It should be part of the formulation
development & stability trials to ensure that activity is likely to remain
through out shelf life.
• Preservative efficacy tests could be single challenge test where
large inoculum of each m.o is introduced into the product & rate of inactivation is
determined by VC at different time intervals, or multiple challenge test,
where the product is exposed to repeated inoculation at set intervals & the
efficiency of inactivation is monitored until the system fails.
• BP, USP & EP describe single challenge test.
• Problems with these tests:
- Does the performance of these tests gives reliable prediction of real in-use
efficiency?
- Repeated cultivation on microbiological media results in reduced
aggressiveness of strains
58. GPMP is concerned with control of ingredients,
plant construction, process validation, production
& cleaning.
QC is part of GMP that deals with testing, specs,
documentation & assessing conformance to specs.
Relying on finished product testing may result in
financial loss if non-compliance was detected at
this late stage, besides microbiological test
methods have poor precision & accuracy, so that
end product testing may not detect failures.
59. Assurance of overall product quality can only come from detailed
specs, control & monitoring of all stages of manufacturing process
not just from testing finished product.
e.g. real estimate of product microbial quality comes from knowledge
of
bioburden of starting raw material, temp record of the granules,
moisture level of the granules, validation record of the machine
cleaning, foil strip packaging & testing of finished tablets.
Each batch should meet all its specification, but this does not
necessary means that all tests should be performed on finished
product. The manufacturer can carry out Parametric release.
Parametric release: is to provide assurance that the product is of
stipulated quality based on evidence of successful validation of the
manufacturing process & review of the documentation on process
monitoring carried out during manufacturing to provide the desired
assurance of product quality.
60. Points to be considered to assure finished product microbial quality:
- Raw materials:
Raw materials to be free from pathogenic microorganisms & with low bioburden. For
ingredients from bovine source, exclude suppliers of materials were BSE is endemic
- Manufacturing plant:
identify areas where m.o. can thrive & colonize to treat & clean them. The design &
construction should allow for thorough cleaning. (machines are made from materials
that can be cleaned & disinfected, some machines are provided with clean-in place
systems)
- Manufacturing process:
some products may require addition of some steps to reduce bioburden or improve
lethal sterilization (e.g. include ultra filtration step rather than conventional
sterilization cylcle)
- Validation to the cleaning system:
to challenge the ability of cleaning system to remove deliberately introduced
contaminant
61. • The current methods for counting & detecting some
microbes in non sterile products have poor accuracy &
precision, examples:
- low no. m.o. sometimes damage the product but can’t
be isolated
- products with active spoilage yields very low microbial
count
- m.o. in high no. but it is not the primary spoilage
agent nor pathogenic
• Uneven distribution of m.o present serious sampling
problem
62. • Pharmacopeias (Ph Eur, BP & USP) have included
quantitative & qualitative standards for non-sterile
products.
- There are maximum total microbial levels & exclusion of
specific m.o depending on route of administration.
- Example: for oral drugs, the count per ml or gram
should be:
no more than 103 total aerobic m.o.
no more than 102 fungi
no E. coli
- Higher levels are permissible if the product contains raw
material of natural origin.
63. • Endotoxin Test:
- Endotoxin (pyrogen) levels in parenterals must be very low to
prevent endotoxic shock.
- Formerly this was tested by injecting rabbits & noting any
febrile response.
- Nowadays the test is performed using Limulus amoebocyte
lysate (LAL) test (gel clot method) where an amoebocyte
lysate from the horseshoe crab Limulus polyphemus reacts
specifically with microbial lipopolysaccharides to give a gel
&opacity even at very high dilutions.
- Tissue culture test are under development where the ability of
endotoxins to induce cytokine release is measured directly
64. • It is impossible to guarantee that a medicine will
never fail under real life conditions, but a proper
quality assurance system must include
procedures to monitor in use performance &
respond to customer complaints in order to
re-evaluate the constructed & implemented
schemes for product safety & check whether
they need modification.