Sterile Product Theory Final Exam Review PDF

STERILE PRODUCT THEORY FINAL EXAM REVIEW Lecture 1 - Unit 1: Introduction to sterile Dosage Form HISTORY of STERILE PRODUCT : FOR BONUS QUESTION 1616 - Dr. William Harvey describes blood Devices made of glass to inject under the 192...

STERILE PRODUCT THEORY FINAL EXAM REVIEW Lecture 1 - Unit 1: Introduction to sterile Dosage Form HISTORY of STERILE PRODUCT : FOR BONUS QUESTION 1616 - Dr. William Harvey describes blood Devices made of glass to inject under the 1926 - 1st official injection solutions added to the circulation of human body skin – subcutaneous (SC) or hypodermic National Formulary needle 1665 - Sir Christopher Wren successfully Late 19th century sterilization taken into 1960s – developments in infusion technology, injects opium into a dog with a quill consideration to prevent infection including LAMINAR AIR FLOW attached to a pig’s bladder 18th to 19th century bacterial growth and 1923 – Florence Seibert discovers fevers 1971 – contaminated IV solutions cause nationwide sepsis discovered by scientists: What are come from PYROGENS from improperly outbreak. FDA, CDC focus attention on IV related their names? distilled water infections Robert Koch, Joseph Lister and Louis Pasteur - One hypodermic needle made by H Wufling Luer (remember that name) - Purpose of Chapter to ensure safe preparation, storage and distribution of compounding sterile products by all healthcare facilities involved in the preparation, storage and distribution of such products (These standards do not apply to the actual clinical administration of these products: such as nursing practices Enforceable in USA only) STANDARDS AND GUIDELINES Health Canada NAPRA CSHP OCP Creation of “The Policy on Developed their own documents: Development of Manufacturing and Compounding “Model Standards for Pharmacy “Guidelines for Adopted the NAPRA Drug Products in Canada” Compounding of Non-Hazardous Preparation of Sterile documents as guidelines Sterile Preparations” Products in Pharmacies” of best practice Defines the terms “compounding” and and “manufacturing” related to “Model Standards for Pharmacy Specifically for All pharmacies involved in sterile and non-sterile products Compounding of Hazardous Sterile pharmacies engaged in sterile compounding now Preparations” sterile compounding inspected by OCP These are the minimum practice Compounding of sterile products and quality standards Includes compliance with falls under section ‘C’ of the Food Adapted from standards such as the Food and Drugs Act and Drugs Act and includes all USP and Health Canada’s GMP drugs scheduled in Schedule C, D USP-NF (Good Manufacturing Health Canada’s GMP (Good - Provincial Regulatory Practices) Manufacturing Practices) Authorities (OCP) use these documents as part of their Compounding will be regulated and standards of practice for include site inspections by each pharmacies engaged in sterile provincial regulatory authority compounding  ALERT!! USP Chapter 797 – LOW, MEDIUM, HIGH RISK PRODUCT LOW RISK LEVEL MEDIUM RISK LEVEL HIGH RISK LEVEL Compounding under ISO Class 5 Includes all low risk level conditions Use of non-sterile ingredients and/or environment using commercially plus one or more of the following using non-sterile devices available ingredients, products, conditions components and devices Combining or pooling multiple doses of Exposure to outside of an ISO Class 5 commercial products to be environment for more than one hour Simple aseptic opening of ampoules, administered to a patient multiple penetrating disinfected times or to multiple patients (batching) closures/stoppers of vials using sterile Inappropriate gloving and gowning needles and syringes Complex aseptic manipulations longer duration of compounding time Storage: Storage : 24 hours or less at RT Transferring/measuring and mixing with 30 hours or less @ room temp 3 days or less refrigerated no more than 3 sterile commercial 9 days or less under refrigeration 45 days or less in a frozen state- no products and no more than 2 entries 45 days or less in a frozen state- no sterility testing into any one sterile container sterility testing Using non-sterile components in Storage of finished product : Combining multi-component admixtures preparing solutions to be sterilized 48 hours or less at room temp using sterile products, syringes and 14 days or less refrigeration automated compounding devices Sterile ingredients measured or mixed 45 days or less in solid frozen state- if in non-sterile devices/containers before no sterility test Sterile containers for admixing sterile being sterilized Single volume transfers using sterile components syringes and needles Simple aseptic transferring using no Examples: Examples: more than 3 commercially ✓ TPN ✓ L.E.T. gel – using non-sterile powders manufactured sterile packages and ✓ Chemotherapy infusion devices infusion or diluent solutions ✓ Batching antibiotics ✓ Nutrient powders, electrolyte powders and other products meant for Examples: parenteral use but made from non- ✓ Reconstitution of sterile powders sterile raw ingredients and mixed in ✓ Measuring, transferring and admixing a sterile/non-sterile containers sterile solution into an IV bag ✓ Prefilled syringes from a sterile container  Characteristics of sterile product STERILITY Absence of viable microorganisms Sterile Assurance Level (S.A.L.) The probability of a viable microorganism found in or on a product following sterilization S.A.L. - the lower the value the greater assurance of sterility S.A.L. VALUE OF 1 = VERY STERILE PRODUCT PARTICULATE MATTER absence of particulate matter includes various types and sources – hair, lint, dust PYROGENICITY Absence of pyrogens Fever producing endotoxins from bacteria STABILITY Prevention of drug degradation- oxidation/hydrolysis/polymerization Dependent on the type of packaging VISCOSITY Key characteristic of ophthalmic preparations Essential to increase contact time of solution and the surface of the eye Ph Commonly a pH of 3-8 for injections pH as close to 7.4 as possible IS ideal Maintaining pH will ensure stability of the preparation TONICITY Must simulate the same tonicity of blood isotonic/hypertonic/hypotonic Tonicity adjusted with sodium chloride – match the pH of your ‘tears’ STERILE PARENTERAL DOSAGE FORMS INJECTION LargestSTERILE sterile parenteral group of products PARENTERAL DOSAGE FORMS Are available as: Aqueous or non-aqueous sterile products administered by: ✓ Solutions IV :STERILE intravenousPARENTERAL DOSAGE FORMS ✓ Powders/solids IM : intramuscular ✓ Suspensions SC : subcutaneous ✓ Emulsion ID : Intradermal IT: intrathecal IS: Intraspinal OPHTHALMICS Includes solutions, suspensions and ointments Sterile and isotonic DIALYSATES Kidney failure Hemodialysis Peritoneal Dialysis IRRIGATION Used to bathe or flush wounds/organs and body cavities Similar packaging as IV solutions ****Always topical never as an injection**** RADIOPHARMACEUTICALS Radioactive chemicals used to diagnose potential condition and/or organ function Different techniques in handling and preparing  SOLUTIONS POWDERS/SOLIDS SUSPENSIONS EMULSIONS Medication in solution of a suitable drug has poor stability in drug suspended in a suitable Insoluble drugs vehicle (water, NaCl 0.9%, dextrose) solution vehicle (aqueous) emulsified for IV for parenteral administration freeze-dried and placed in in solution ready to administration Small volume Parenterals (SVP) solution at time of use – administer Reduce drug toxicity as small as 0.5mL reconstitution administered always IM Large volume Parenterals (LVP’s) never IV as large as 3000 mL Components of Sterile Products VEHICLES No therapeutic/toxic activity Water for Injection Sterile Water for Irrigation Serve as solvents and carriers most widely used vehicle Prepared by distillation and/or reverse of active drug prepared by distillation/reverse osmosis Includes aqueous and non- osmosis Packaged and sterilized in containers of aqueous types must meet purity requirements 1-3L sizes with screw cap Most common is water absence of pyrogens Labeled not for injection/only for Must meet compendial must be clear and colorless with a irrigation standards - i.e. USP/BP pH of 5-7 Contains no preservatives AQUEOUS Water for injection Sterile Water for Injection (SWFI) Bacteriostatic Water for Injection Sterile VEHICLES/ STERILE water for injection Sterilized water for injection and water for injection containing 1 or more WATER BACTERIOSTATIC water for suitable packaged suitable bacteriostatic agents injection Contains no preservatives Common bacteriostatic agents include: Sterile Water for IRRIGATION benzyl alcohol/parabens Compatibility and potential adverse clinical/toxicity issues ISOTONIC ISOTONIC ISOTONIC VEHICLES ISOTONIC VEHICLES NaCl 0.9% for injection Sodium Chloride for Injection 0.9% Sodium chloride for IRRIGATION NaCl 0.9% for IRRIGATION Commonly referred to as Normal (not injection) BACTERIONSTATIC NaCl Saline-NS No preservative 0.9% Bacteriostatic Sodium Chloride Only for irrigation/topical Dextrose 5% With preservative use for wounds not for injection Lactated Ringers Vehicles ***Both are Sterile and pyrogen Aqueous free*** ISOTONIC VEHICLES Dextrose 5% Injection Lactated Ringer’s Injection  Lecture 2 - Unit 2 : Infection Control Define: Mutualism/Commensalism/Parasitism (Symbiotic Relationships) mutualism commensalism parasitism ✓ Both species benefit ✓ One organism or species benefits ✓ One of the species exists at the ✓ DIGESTIVE BACTERIA and the other neither benefit OR expense of the other Inhabit GI of vertebrates & aid in suffers The organism that benefits: parasite digestion of food not able to be Indigenous microflora in/on The organism that suffers: host digested humans Tapeworm Bacteria obtain nutrients from Staphylococcus on the skin Fleas food eaten Scabies Bacteria produce by-products that are beneficial to humans Symbiosis: Close association between two organisms of two different species - no harm and at least one of the organisms will benefit from this association The Three Types of Symbiotic Relationships ORGANISM 1 ORGANISM 2 EXAMPLE MUTUALISM BENEFITS BENEFITS Bacteria in human colon COMMENSALISM BENEFITS NEITHER BENEFITS NOR IS HARMED Staphylococcus on skin PARASITISM BENEFITS IS HARMED Tuberculosis bacteria in human lung DEFINITIONS Micro-organism Small living organism Includes bacteria, protozoa, algae and fungi Micro = small May or may not cause disease Not visible to the naked eye Majority only visible under a microscope Pathogen/Pathogenic Microorganisms that cause disease Approximately 3% of known micro-organisms Non-Pathogen/Non-pathogenic Micro-organisms that DO NOT cause disease Approximately 97% of known micro-organisms PATHOGENIC or NON-PATHOGENIC The ability to cause OR not cause disease Opportunistic Pathogens Have the potential to cause infection or disease by invading a part of the human body Indigenous microflora (normal flora) Inhabit on or within the human body Transient-present for a short period of time then disappear Resident – permanent residence in the body ~ 10 trillion of 500-1000 different species Pyrogens Pyrogens are substances, typically produced by bacteria, viruses, or damaged cells, that can cause fever when introduced into the body. They trigger the body's immune response, leading to an increase in body temperature as part of the defense mechanism.  Bacteria – all aspects - types, characteristics, growth conditions etc. BACTERIA ✓ Over 5000 species Most non-pathogenic Small number are pathogenic Classified by 3 common characteristics SHAPE GRAM STAIN ABILITY TO USE OXYGEN BACTERIA - CLASSIFICATION Simplest way of classifying bacteria is by performing a gram stain viewed microscopically Gram positive (+ve) Bacteria stains blue to purple following Gram staining Gram negative (-ve) Bacteria stains red/pink following Gram staining BACTERIA – GROWTH ABILITY TO USE OXYGEN CONDITIONS Aerobic Thrive and grow in an oxygen-rich environment Anaerobic No oxygen needed to grow and multiply BACTERIA – GROWTH TEMPERATURE: pH CONDITIONS Level of acidity/alkalinity affects growth THERMOPHILES - high temperatures 40-70°C ACID-ophiles – ACIDIC ENVIRONMENT HYPERthermophiles - above 100°C Prefer pH of 2 - 5 PSYCHROPHILES - cold temperatures 0- 32°C ALKALI-philes - ALKALINE ENVIRONMENT PSYCHRODURIC - Prefer warm but can endure cold Prefer pH > 8.5 temperatures Barometric Pressure MESOPHILES - Like moderate temperatures15-43°C Baro-philes - High atmospheric pressure COMMON Gram negative cocci PATHOGENS Neisseria gonorrhoeae Neisseria meningitis Gram positive cocci Staphylococcus aureus/streptococcus pyogenes opportunistic Fungi – types, characteristics etc. ( I CAN’T FIND SLIDE ON FUNGI) ? Pathogenic Fungi – Candida Albicans  Viruses – types, characteristics etc. VIRUS Not common contaminants of sterile products Not considered microbes Can infect all living organisms including bacteria can not reproduce on their own – need to invade a host Sources of pyrogens and particulate matter PYROGENS Clinical Side Effects ✓ Soluble in water Lead to septic shock ✓ Insoluble in organic solvents Low blood pressure ✓ Compounded sterile products from non-sterile Reduction of mental alertness/confusion components should be tested for pyrogens Rapid breathing ✓ Pyrogenic reactions indicate poor aseptic preparation Chills & fever technique Organ failure Blood clots Death Sources of Pyrogens ELIMINATION ✓ Water-solvent –most common source ▪ Once present extremely difficult to eliminate ✓ Containers/devices used to prepare a product and/or ▪ Best way to prevent is to not introduce pyrogens into the package a product product/components ✓ Chemicals used in preparation of OTHER METHODS: product Sterilization of equipment Use of acidic/alkaline solutions Rinsing with pyrogen free water Removal of Use of pyrogen free sterile ingredients equipment, containers and closures pyrogens Same environmental and hygiene controls as for particulate matter Prevent entry during compounding by aseptic technique De-pyrogenation and sterilization of compounding equipment Use of dry heat, autoclaving and chemical methods to remove pyrogens from equipment Particulate matter Particular SOURCES Removal of particular Matter TYPES matter Vehicles-solvents Compounding under ISO class 5 Fibers Drug-active ingredient environment Glass Environment Aseptic manipulation of Rubber Equipment components Metal Packaging Use of sterile commercial Plastic Container & closure components Undissolved substances Personnel - aseptic technique Personal hygiene Hair proper attire controlled environment of compounding area filtration  Lecture 3 - Unit 2 (continued): Causes, prevention and elimination of micro-organisms (pathogens) DEFINITIONS 😉 STERILIZATION the process of eliminating or killing all forms of microbial life, including bacteria, viruses, fungi, and spores, from an object or surface. Unlike disinfection, which reduces the number of harmful microorganisms, sterilization ensures complete eradication 2 categories: ✓ Physical Anti-Microbial Method ✓ Chemical Anti-Microbial Methods DISINFECTION Process using a disinfectant to reduce/inactivate/destroy disease producing microorganism. Disinfection does NOT destroy spores!! DISINFECTANT A chemical agent that inhibits infection by reducing the number of microorganisms, such as bacteria. Most disinfectants are used on surfaces and/or equipment Typically, more potent than antiseptics because they are used on inanimate surfaces where higher concentrations are tolerable. Example: Bleach or Lysol is used to disinfect hospital floors or bathroom surfaces. ANTISEPTIC A chemical agent used on living skin or mucous membranes (skin or wounds) to kill microorganisms Since antiseptics are applied to the body, they are gentler to avoid causing irritation or harm Example: Hydrogen peroxide ANTISEPSIS the process of using antiseptics to kill micro-organisms COLD STERILANT a chemical agent used to achieve sterility in medical and laboratory equipment without the use of heat valuable for materials that cannot withstand high temperatures (autoclaving) COMMUNITY ACQUIRED Infections that are contracted outside of healthcare settings, usually in everyday environments like homes, schools, or workplaces. INFECTIONS Examples: ✓ MRSA-Methicillin-Resistant Staph Aureus ✓ VRE – Vancomycin – Resistant Enterococci ✓ Norovirus-stomach flu ✓ Influenza, pneumonia, tuberculosis NOSOCOMIAL INFECTIONS Infections acquired during a stay in a healthcare facility (such as a hospital) that were not present at the time of admission. AKA hospital-acquired infections Example: MRSA, surgical site infections USA statistics: 2 million people/year 33% considered preventable IATROGENIC INFECTIONS infections that occur because of medical treatment or procedures Caused by: ✓ Medical interventions ✓ Contaminated equipment ✓ Medications ENDEMIC A disease regularly found and consistently present in a particular geographic area or population. Cases may increase or decrease but never eliminated Incidence at any particular time depends on: ✓ Environmental conditions ✓ Genetic susceptibility of population ✓ Behavioral factors ✓ Virulence and source of infection ✓ Immunizations Example: Malaria is endemic to parts of Africa, chicken pox, common cold PANDEMIC Across many countries- possibly worldwide affecting a large number of people globally. Occurs in epidemic proportions Involves a specific disease Examples: COVID-19, HIV/AIDS EPIDEMIC AKA an outbreak A sudden increase in the number of cases of a disease above what is normally expected in a specific area. Present in a specific population/region Number of people infected could be small or large Examples: Norovirus, Legionnaire’s disease, West Nile virus, Ebola SPORADIC occur infrequently and irregularly in a population. These cases are isolated and scattered without a predictable pattern. Population of a particular geographic area Can become epidemic Controlled by vaccinations & good public health Examples: Measles, Mumps Nosocomial infections – Sources, types of infections and pathogens, contributing factors SOURCES the process of eliminating or killing all forms of microbial life, including bacteria, viruses, fungi, and spores, from an object or surface. Unlike disinfection, which reduces the number of harmful microorganisms, sterilization ensures complete eradication 2 categories: Physical Anti-Microbial Methods Chemical Anti-Microbial Methods TYPES OF 1. Urinary tract infections 2. Surgical wound infections INFECTIONS 3. Lower respiratory infections 4. Blood stream infections (COMMON) 5. Gastrointestinal infections COMMON Gram + positive cocci Gram - negative bacilli Staphylococcus aureus E. Coli PATHOGENS Enterococcus species Klebsiella species CONTRIBUTING ✓ Increasing number of drug-resistant pathogens ✓ Failure of personnel to follow infection control guidelines FACTORS ✓ Poor hygiene procedure and aseptic technique ✓ Lengthy & complicated surgery ✓ Overcrowding and staff shortages ✓ Lack of training and/or qualified personnel ✓ Economic restrictions ✓ Increased number of immuno-compromised patients ✓ Increased usage of immunosuppressant agents ✓ Inappropriate use/processing of medical devices Types of Physical anti-microbial methods – describe, define DEFINITION involve techniques that utilize physical agents to kill, inhibit, or remove microorganisms. METHODS DRY HEAT MOIST HEAT AUTOCLAVING FREEZE-DRYING FILTRATION COLD METHOD DEFINITION APPLICATIONS Dry Heat Uses hot air to sterilize materials by Used for materials that cannot be exposed to moist heat heating them at high temperatures in a Useful for items that are stable at high temperatures hot air oven Suitable for medical devices made of steel, glass or some 160- 165°C for 2 hours or powders, oils and waxes 170°C-180°C for 1 hour PROS CONS Nontoxic Time consuming Not harmful to the environment slow rate of microbial kill Easy installation of hot oven cabinet high temperatures not suitable for most material Low operating cost Not suitable for majority of parenteral and/or heat-sensitive Not corrosive to metals and sharp products instruments METHOD DEFINITION Moist Involves the use of steam or boiling water to sterilize equipment Heat Lower temperatures No pressure Suitable for devices, food, and some Ophthalmic products METHOD DEFINITION Cold Includes refrigeration/freezing Mainly for inhibition of microbial growth Thawing allows bacterial growth to start again or resume ✓ Does not kill all microorganisms; some may survive freezing. METHOD DEFINITION APPLICATIONS Autoclaving form of moist heat sterilization using Used to sterilize items that can be penetrated by steam under pressure water vapor (pressurized steam) 121°C and steam pressure of 15 lbs/sq for 15-20 minutes). Preferred method of sterilization for: Aqueous solutions Kills all vegetative bacteria, spores and Suspensions viruses Sealed glass ampoules High density plastic tubing – administration sets PROS CONS More effective than dry heat not suitable for containers that are dry sealed Rapid penetration through wrapped items not suitable for oils and waxes Easily controlled sterilization process Temperature-sensitive tape – easy identifier METHOD DEFINITION Freeze Drying A dehydration process that removes moisture from materials o Dehydration & freezing in a vacuum (Lyophilization) Sterile powders Does not kill microorganisms but prevents them from reproducing Potential reactivation of pathogens if their environment becomes favourable for reproducing o Once freeze-dried pathogens are rehydrated (e.g., by adding water or placing them in a suitable medium), they can regain metabolic activity and proliferate Freeze-drying is commonly used for vaccines, antibiotics, and other biological products to extend shelf life METHOD DEFINITION Filtration Sterile membrane filters of a pore size of 0.22 microns or smaller, effectively removing bacteria and some larger viruses from solutions. Use in many aseptic compounding procedures administration of parenteral products that are sensitive to heat or steam Two types: o Hydrophobic – filter gases & solvents ▪ These filters repel water and are ideal for applications involving non-aqueous solutions o Hydrophilic – aqueous solutions ▪ These filters allow water to pass through  Types of Chemical anti-microbial agents – advantages/disadvantages METHOD DEFINITION LOW LEVEL Also referred to as carbolic acid Potent anti-microbial activity Phenols Minimal use as may be corrosive Cresol group- Lysol® Inanimate object disinfection- surfaces Not effective against spores PROS CONS Leaves residual film – maintains contact with surface which not to be used in neonatal units will extend time to increase killing of micro-organisms can not be used on or near food When used with detergent provides one-step because it will can be absorbed through skin or stoppers of vials clean but also disinfects METHOD DEFINITION INTERMEDIATE LEVEL 50-80% concentration Disinfection/antisepsis Inanimate objects Alcohol Skin antisepsis effective against a wide range of microorganisms, including bacteria, fungi, and some viruses. Recommended for ISO Class 5-8 environments Examples: Ethyl/Isopropy PROS CONS No residue Not effective against spores Alcohol evaporates quickly, which can reduce Needs sufficient contact time residue on surfaces and make it suitable for use on The effectiveness of alcohol as a disinfectant depends on its skin and instruments. concentration. Fast acting Alcohol works quickly to kill microorganisms, typically within 30 seconds to a few minutes Non staining METHOD DEFINITION INTERMEDIATE LEVEL Chlorhexidine Disinfectant and antiseptic Aqueous and/or tincture Biguadines class - chlorhexidine Different concentrations- 0.05%- 20% PROS CONS Very effective against most bacteria Not effective against bacterial spores has a prolonged residual effect, meaning it continues to Can cause staining inhibit microbial growth even after application At high concentration & prolonged contact, can cause irritation  METHOD DEFINITION HIGH LEVEL highly effective Example: formaldehyde, glutaraldehyde ALDEHYDES PROS CONS Highly effective because it can sterilize and kill both Need of ventilation and proper attire vegetative bacteria and spores and viruses Highly irritating fumes and toxic Non-corrosive METHOD DEFINITION HIGH LEVEL Stabilized for better effectiveness Can sterilize in 30 minutes Can be combined with other disinfectants HYDROGEN PEROXIDE PROS CONS strong oxidant can be corrosive fast acting reduced ability to infiltrate onto surfaces decomposes down to oxygen and water METHOD DEFINITION HIGH LEVEL chemical solutions that are used to sterilize medical instruments and equipment at room temperature (or lower temperatures), without the need for heat-based sterilization PERACETIC ACID (cold sterilant) methods PROS CONS Rapid acting Can corrode metal but additives and pH modifications can No harmful decomposition products minimize this effect Leaves no residue Can be combined with hydrogen peroxide  Transmission of pathogens – different types 1. DIRECT Skin to skin contact DIRECT MUCOUS-TO-MUCOUS MEMBRANE CONTACT KISSING AND/OR SEXUAL CONTACT o (STIs) like HIV, herpes, or gonorrhea. o Epstein-Barr virus (mono) 2. AIRBORN DROPLETS Respiratory secretions o infected person coughs, sneezes, talks, breathes o influenza, COVID-19, and tuberculosis (TB) 3. FECAL MATERIAL food, water, or surfaces contaminated with fecal matter are ingested, often due to poor sanitation or hygiene practices. o Gastrointestinal infections: cholera o Parasites 4. FOMITES Fomites are inanimate objects or surfaces that can carry and transmit pathogens when touched. o stethoscopes o bedding o surgical equipment Improperly sterilized medical instruments can transmit pathogens like HIV, hepatitis B and C  Lecture 4 - Unit 3: Contamination control/Facility Engineering control systems Structural and engineering requirements of facilities Requirements Specifically constructed Standards & Guidelines: regulatory and professional recommendations NAPRA CSHP Must be in a separate area from other pharmacy facilities Air handling/temperature/humidity control Control traffic of personnel entering and leaving Specific areas for all Personnel preparation (PPE &handwashing) Product compounding aspects of sterile Product labeling compounding Final product release (checking) Documentation (Needs have a specific area for the following:) Controlled Rooms Environment is controlled & documented, NAPRA expects controlled rooms to fall under certain conditions entrance only allowed to people trained in their proper use (hand hygiene, garbing, cleaning) the only activities taking place are those related to the compounding of sterile preparations (NAPRA) Ceilings, walls, floors, doors, door frames, shelves, counters and cabinets must be smooth, impervious/waterproof, free from cracks and crevices, non-porous, resistant to damage from cleaning & disinfecting products Under positive pressure, to keep contaminants from entering controlled areas Avoid brining in particle shedding items such as cardboard, paper  Anteroom vs clean room ANTEROOM CLEANROOM Definition serves as a buffer zone between uncontrolled or less controlled Primary workspace, ultra-clean areas and the highly controlled clean room environment. environment physically separated from the only work related to sterile compounding - control the types of pharmacy to reduce the risk of contaminants entering the cleanroom contaminants Should contain hands free sink, soap dispenser, nail, picks, hand drying system, mirror, garbage, eyewash station, PPE Purpose To minimize contamination in the clean room by serving as a used for sterile compounding staging area where personnel can don protective clothing (such To provide a controlled, sterile as gowns, gloves, masks). environment where contamination is Supplies may be prepared or stored here before being moved minimized. into the clean room. ISO class 8 7 under positive pressure under positive pressure 2 doors (one to cleanroom & uncontrolled area), only one door contains PEC (Primary Engineering opened at a time Control) Cleaning, temperature, pressure & humidity documented daily devices that provide a localized Environmentally sampled every 6 months ultra-clean air environment, Extra anteroom separated into two spaces by a VISIBLE demarcation using HEPA filters, to protect the Information line product and the environment o dirty side: at the entrance to the anteroom from the from contamination non-controlled area cleaning, temperature, pressure & o clean side: beside the dirty area, clean room on the humidity documented daily other side environmentally sampled every 6 Carts used to bring supplies into the anteroom from outside the months controlled area must not cross the line of demarcation ceiling lights flush with the ceiling and line used to don and doff shoe covers sealed no sink or floor drains access through anteroom & restricted only to staff working in the room pass-through windows and/or airlocks no food and/or drin  CUSTOM MODULAR DESCRIPTION Built from the ground up to meet highly specific Prefabricated and assembled on-site. design and performance requirements. Hard-wall for high volume operations These are usually permanent installations Soft-wall for low volume operations PROS offer maximum flexibility in terms of layout, more flexible materials, and features Can be easily reconfigured, expanded, or relocated if rigid strong structures needed quicker to install less expensive than custom no physical maintenance - i.e painting CONS most expensive to construct not as durable as custom built space limitations limited flexibility for expansion high maintenance  ISO classes of clean rooms ISO (International Organization for Standardization) classes define the cleanliness level of air in controlled environments based on the concentration of airborne particles determined by the number and size of particles per cubic meter of air ANTEROOM CLEANROOM PEC DCA (Primary Engineering direct compounding area Control) LAFH, BSCs, isolators ISO CLASS N/A Work surface is 6 inches inside the hood with 8 7 5 HEPA filtered air Particle For particles For particles larger For particles larger N/A Requirements larger than 0.5 than 0.5 microns than 0.5 microns the microns the max the max is 352,000 max is 3,520 (the maximum is 3,520,000 particles per cubic particles per cubic allowable particles per meter of air. meter of air. particle counts cubic meter of air. for particles)  Laminar Airflow Hoods – various types, airflow, ‘first air’ LAMINAR AIR FLOW Also referred to as” Unidirectional Airflow Concept” refers to the movement of air in parallel, uniform layers with minimal turbulence air travelling at a constant velocity in parallel streamlines and in a single direction pushed through a HEPA filter at constant velocity in either horizontal or vertical direction over and away from the product Creates clean/bacteria/particulate free environment in cleanroom and LAFH: NOT STERILE FIRST AIR “A critical area within an ISO Class 5 controlled area where critical sites are exposed to unidirectional HEPA-filtered air” refers to the clean, filtered air that comes directly from the High Efficiency Particulate Air (HEPA) filter. This air is the most sterile and particle-free Materials and products must be placed on the work surface in direct airflow of the HEPA filter Nothing should obstruct the space between the HEPA filter and the sterile products A continuous flow of filtered air ensures that contamination of critical sites is eliminated HEPA FILTER “High Efficiency Particulate Air “- Filter used to remove contaminants like dust, bacteria, and other particles from the air, ensuring the environment remains sterile or contaminant-free. HEPA engineering control is used to maintain sterility & prevent contamination during the compounding of a sterile preparation Characteristics & Efficiency A filter enclosed in a rigid frame having a minimum particle collection efficiency of 99.97% can remove small contaminants such as bacteria but it CANNOT remove any type of vapour/gas  LAMINAR AIR FLOW HOOD TYPES HORIZONTAL VERTICAL AIRFLOW DIRECTION Air flows from the back of the hood towards the Air flows from the top of the hood downwards front, across the work surface. towards the work surface. PROS Less turbulence: Because air moves in a Helps protect the product from potential straight path, it is less likely to be disrupted by contamination from operators, as the air flows objects on the work surface downward, preventing particles from falling onto the work surface. Easy access: Horizontal airflow hoods tend to allow better access to the workspace from Safety: The airflow does not blow directly toward the above, making it easier to work with larger operator, reducing the risk of contaminating the equipment or instruments. operator or disturbing sensitive materials. CONS Airflow directed toward the user: The air, along Limited space: The vertical design may limit with any potential contaminants, flows toward overhead access for large instruments or equipment. the operator tends to have slightly more turbulence than Preferred for non-hazardous powders horizontal LAF. APPLICATION where protecting the product from useful when working with hazardous materials or contamination is more important than chemicals that need to be safely ventilated away protecting the operator. from the user ISO CLASS 5 5 EXTRA INFO 1) Room air is introduced through the PRE- Fans & filter positioned in the ceiling FILTER Suitable for fine powders 1) Room air is introduced from 2 areas – 2) Pre-filter will remove large particles and Top of the hood contaminants from the room air before Intake vents found directly in front of the it passes through the HEPA FILTER work surface area (in BSC) 3) The PRE-FILTERED AIR and 2) The room air introduced through the pre-filter CONTAMINATED AIR are then forced is passed through the HEPA filter as vertical through the HEPA filter by the motor airflow down to the work surface blower assembly 3) The room air introduced through the intake 4) The air stream is passed through the vents is considered contaminated and is HEPA filter in a HORIZONTAL forced through an external venting system DIRECTION  POSITIVE PRESSURE Positive pressure refers to a controlled environment where the air pressure inside a room or space is higher than the surrounding areas. This is achieved by pumping filtered, clean air into the space, ensuring that when doors or openings occur, air flows outward rather than inward REVIEW diagrams of LAFH’s and cleanroom set up TEST 2 REVIEW CONTINUES  LECTURE 5: UNIT 4 Aseptic techniques Principles – introduction Definition of Aseptic Technique Many areas of medical practice use aseptic technique Aseptic derived from two Latin words Aseptic technique principles apply to all aspects of sterile product preparation “a” = without ❑ Personnel and personal protective equipment “sepsis” = infection ❑ Environment ❑ Cleaning of equipment and containers Aseptic technique is the procedure of manipulating sterile ❑ Critical sites preparations, components, packaging components and ❑ Needles and syringes administration devices without contaminating the finished product ❑ Manipulations ❑ Organization ❑ Handling of hazardous material Administration devices PERSONNEL: General Principles Personal Protective Equipment NAPRA 6.6.2.2 PPE donning and doffing must be documented in policies and procedures Dirty side of line of demarcation (LOD): ✓ Hair net ✓ Beard net (if applicable) ✓ Face mask While stepping over the LOD: ✓ Don shoe covers NAPRA set the minimum standards, but hospital can add extra steps to it PERSONNEL: General Principles Personal Protective Equipment NAPRA 6.6.2.2 Perform aseptic handwash o Warm running water use nail pick o Wash hands and forearms to elbows for at least 30 seconds o Rinse with warm water o Pat dry with lint-free, disposable towel ✓ Apply alcohol-based hand rub ✓ Don gown with closure at the neck and cuffs ✓ Apply alcohol-based hand rub Don sterile gloves and disinfect with sterile 70% IPA PERSONNEL: Personal Protective Equipment (PPE) BONNET hair and head are the one of the dirtiest parts of your body long hair tied back and ensure all hair is tucked into the bonnet SHOE COVERS worn over regular shoes shoes are often “work dedicated” only not worn outside MASKS Covers mouth, nose Prevents potential contamination due to saliva droplets and particulate matter Controls mouth secretions during talking, sneezing, coughing Sneezing/coughing – should replace mask immediately Personnel with cough and/or upper respiratory infections must not work in compounding area GOWNS ▪ Disposable - often discarded at the end of the working day ▪ Prevent contamination of work area from shedding particles of skin and clothing ▪ Pharmacy staff, nursing, physicians, housekeeping ▪ Not to be worn outside of the environment that you are working Pharmacy – not to be worn outside of the anteroom/cleanroom Nursing/Physician – remove isolation gown immediately after leaving patient room Criteria for GOWNS ❑ Disposable ❑ Made of lint-free material ❑ Have low permeability fabric – repel liquid ❑ Have a solid front ❑ Long sleeves ❑ Tight fitting elastic/knit cuffs ❑ Chemotherapy gowns - provide adequate protection from hazardous drugs GLOVES Not a substitute for proper aseptic technique Reduce touch contamination Dry skin cells shedding Latex free, nitrile, neoprene, polyurethane Should fit properly - Loose gloves tear easily & may interfere with manipulations GLOVES Permeability depends on: ✓ Drug ✓ Gloving material ✓ Thickness of gloves ✓ Time exposure Periodic disinfection with 70% isopropyl alcohol - reduces bioburden on surface of gloves EYE PROTECTION Prevent potential exposure of eyes to hazardous substances Not commonly used for aseptic manipulations but is recommended for cytotoxic spill clean up  HAND WASHING Touch contamination – most common form of contamination Bacteria – hides in fingernails, hair follicles of back of hand, skin pores Wash prior to gloving with soap and/or disinfectant soap- preferable type that does not alter pH of skin Hand Washing agents: Choice based on killing ability and residual presence/effect Popular ones include: Isopropyl/ethyl alcohol hand rinses Triclosan 2% - 4% Chlorhexidine – antiseptic NAPRA 6.6.2.1 ❑ Under warm running water, use a nail pick to remove debris from underneath fingernails. ❑ Wash hands and forearms up to the elbows with soap and water, for at least 30 seconds. Do not use brushes. ❑ Rinse with water. ❑ Dry hands and forearms with disposable, lint-free towel. ❑ Dispense alcohol-based hand rub (ABHR) with persistent activity onto one palm. ❑ Immerse fingertips of the other hand into the ABHR. ❑ Cover the forearm of the other hand with ABHR until the ABHR evaporates. ❑ Repeat with other hand and other forearm. Hand-washing sequence must be documented in policies and procedures EQUIPMENT: Laminar Airflow Hood Continuous operation – 24 hours/7 days a week If LAFH has been turned off wait 30 minutes after the LAFH has been turned back on before cleaning and compounding Cleaning of LAFH and BSC Disinfection - multiple products Frequency – see Lecture #4 slide 46, 47 Clean twice daily, and before each preparation. Introduction of Items into the Cleanroom All items must be removed from cardboard containers Items disinfected with 70% sterile IPA wipes prior to introduction to cleanroom via the pass through or anteroom Sterile 70% IPA wipes should be regularly changed during disinfection All items for each preparation are separated in plastic or stainless-steel containers Stainless steel or plastic containers to be disinfected before use Non-paper items entering hood must be wiped with low-shedding sterile 70% IPA wipes Items are to be placed 6 inches inside hood Open wrapped sterile items past 6 inches and place on work surface Placement of items should be in a way that first air will not be obstructing critical sites All items for preparation should be in the hood to minimize movement in the hood, but do not overcrowd work area Gloves disinfected with sterile 70% IPA before entering the hood and after touching a contaminated surface. Allow to dry before starting preparations  EQUIPMENT- Laminar Airflow Hood ▪ Direct compounding area (DCA) minimal movement to reduce air turbulence ▪ Object positioning- within 6 inches of outside edge of work surface ▪ Direct airflow – “first air” ▪ Supplies off to the side of DCA ▪ Diluent bag not hanging over work surface ▪ Critical sites in first air ▪ Not cluttered ▪ Waste container and sharps to side of DCA Principles of working within the LAFH include: ✓ No jewelry ✓ No make-up ✓ No sneezing, coughing inside working area of LAFH ✓ No food or drinks ✓ Avoid unnecessary movements ✓ Only supplies required for compounding placed in LAFH (no pens, pencils, paper) ✓ Labelling of products performed outside of the LAFH ✓ Annual Testing and certification by qualified companies Equipment & Supplies: CRITICAL SITES When performing aseptic technique, the operator must avoid contamination of CRITICAL SITES. This includes: ✓ Point of entry into sterile container ✓ Injection sites on administration sets ✓ Exposed needle shaft and hub ✓ Syringe tip ✓ Syringe plunger ✓ Luer- lock connections and injection ports on IV administration sets Critical sites are any opening or surface that can provide a pathway between the sterile product and the environment Critical sites should not be touched and always in constant flow of first air First air is the undisturbed air from a HEPA filter that is essentially particle free SYRINGES Plastic or glass Glass syringes: may provide storage of medications for extended periods Plastic - advantages: ✓ less expensive ✓ disposable ✓ unbreakable SYRINGE - structure Barrel & plunger Plunger fits inside barrel flat end at one end, rubber piston at the other end Barrel has two open ends Syringe tip Barrel collar to prevent plunger slippage though fingers during use SYRINGE: ribs of the plunger ribs of the plunger must not be touched (critical site) only the flattened end of the plunger can be touched sizes vary from 1 mL to 50 mL size must allow room for volume adjustments and air removal as general rule dose should be at least a minimum of 20% of the syringe capacity and no more than 75% full SYRINGE Needle tip Luer-lock Slip tip Two critical sites Syringe tip Shaft of plunger Outer wrapping to protect sterile status of syringe Outer wrap must be removed inside the LAFH to maintain sterility May have needles permanently attached Insulin syringes Vanish point SYRINGES – calibrations Be sure to note calibration marks for different sizes of syringes 1cc - 0.01mL 3cc - 0.1mL 5cc - 0.2mL 10cc - 0.2mL 20cc -1mL 30cc -1mL 50cc -1mL May also have calibration marks in units (insulin) Equipment & Supplies NEEDLES Length depends on site of administration & depth of injection Length ranges between 3/8 - 3 inches Gauge depends on viscosity of fluid to be injected or withdrawn Gauge ranges between 13-32 gauge larger the number small the lumen diameter Needles can be changed every 3-5 punctures if not contaminated NEEDLES ▪ individually packaged ▪ hub is colour coded to identify gauge ▪ shaft or cannula usually stainless steel – silicone coated ▪ never touch any part of the needle ▪ needle cap to stay on until needle is in use ▪ filter needles remove particles withdrawing from glass ampoules  Equipment &Supplies DISPENSING PINS/DEVICES ▪ Devices used to withdraw solutions from vials or bags ▪ Prevent multiple needle punctures ▪ Vented for pressure equalization in vial ▪ Venting through hydrophobic filter ▪ Be aware of critical sites Equipment & Supplies FILTERS/FILTERING DEVICES ▪ disposable ▪ various size disc filters ▪ 0.22 micron ▪ 0.45 micron ▪ 5 micron ▪ thin membrane filter ▪ sterilize solutions ▪ certain drugs required to be filtered before administration ▪ can administer solutions through an in-line filter on IV administration sets Equipment & Supplies FILTERS/FILTERING DEVICES SELECTION CRITERIA INCLUDE: ❑ PORE SIZE ❑ COMPATIBILITY ❑ FLUID VOLUME ❑ PARTICULATE LOAD Equipment & Supplies FILTERS/FILTERING DEVICES SELECTION CRITERIA: PORE SIZE ❑ Determines size of particles retained by the sieving action of the filter ❑ Clarity of the solution (glass removal from ampoule) requires entrapment of particles 5 micron or smaller ❑ Bacteria retention (removal of bacteria) requires a 0.22-micron filter ❑ Sterilization by using a membrane filter is not absolute FILTERS/FILTERING DEVICESSELECTION CRITERIA: COMPATIBILITY ✓ Most available filters are generally compatible with current pharmaceuticals ✓ Organic solvents can cause swelling and damage filters FILTERS/FILTERING DEVICES Selection criteria: FLUID VOLUME ▪ surface area of the filter will optimize filtration rate ▪ the larger the diameter the greater the retention of solution in the filter (this is considered “lost or wasted” solution) ▪ filters that have a 25-47 mm in diameter are suitable for small volumes – less solution lost in the filter ▪ large volumes (10 mL to 1 L) will often require a filter of 50 mm in diameter FILTERS/FILTERING DEVICES Selection criteria: PARTICLE LOAD ▪ greater the number of particles in solution the more difficult it is to filter ▪ particles will clog the filter ▪ multiple filters will be required to complete the filtration process  Parenteral Dosage Forms Equipment & Supplies: Parenteral Dosage Forms VIALS Single use (preservative free) or multi- dose (preservative) Basic components: Glass or plastic container Stopper or rubber closure Closure secured by aluminum or stainless-steel ring with a flip off cap Critical site is the central rubber stopper Needle entry technique to avoid coring of the rubber stopper ( 45-degree angle) VIALS DISADVANTAGES AND RISK FACTORS: ADVANTAGES: ▪ entering a vial with needle/syringe multi-dose and/or single dose ▪ touch contamination reusable when properly stored ▪ airborne contamination due to disruption of LAFH air easier to manipulate than ▪ transfer of contaminants from rubber stopper and other surfaces ampoules ▪ coring of the rubber stopper - particle contamination Common Preservatives for Multi-Dose Vials ❑ Benzoic acid ❑ Phenol/Cresol ❑ Chlorobutanol ❑ Methylparaben ❑ Benzyl alcohol multi-dose vials must be dated once opened stable for up to 28 days after first puncture – dependent on manufacturer’s recommendations may be punctured safely up to 5 times – dependent on the size of needle use dispensing pin to reduce punctures  Equipment & Supplies: Parenteral Dosage Forms DOUBLE CHAMBERED VIALS sterile powder of drug and diluent packaged in same vial in separate compartments no need to withdraw diluent for reconstitution compartments separated by a rubber plug apply pressure on top closure of vial to dislodge rubber plug and mix diluent and powder commonly single use Equipment & Supplies: Parenteral Dosage Forms STERILE POWDER lyophilized or freeze- requires reconstituted VIALS dried powder reconstitution solution stability of solution not the same as the expiration diluents are commonly date of the vial (powder) sterile water or sodium chloride 0.9% solution must be stored as manufacturer recommends AMPOULES (glass) DISADVANTAGES AND RISK FACTORS ADVANTAGES touch contamination improved stability particle contamination - glass improved security - tamper proof airborne contamination due to open or exposed drug reduced potential for contamination by coring since no injury to operator & potential damage to the HEPA filter rubber stopper once opened solution cannot be stored for future use POLYAMPS made of plastic varied sizes commonly 10 mL and 20 mL less hazardous than glass ampoule access to solution contents direct with needle through opening or using a syringe with no needle with a luer-lock connection no need for filter needles not appropriate for all drugs- plastic - compatibility issues  MINIBAG PLUS and ADDVANTAGE SYSTEMS special packaging vial can be attached to IV solution drug reconstitution can be performed by nursing staff just prior to administration MINIBAG PLUS SYSTEM ADD-VANTAGE SYSTEM does not require vials with adaptable rubber stoppers. requires specifically manufactured vials by Pfizer that port of bag will fit all available sizes of vial rubber stoppers will only fit the ADDVANTAGE IV solution adapter common IV solutions and sizes available available drug option is limited NaCl 0.9% and Dextrose 5% NaCl 0.9% and Dextrose 5% Equipment & Supplies: Parenteral Dosage Forms PRE-FILLED DISPOSABLE SYRINGES has attached needle or may require assembly drug in solution ready to be administered commercially available pharmacy prepared PFS as well ideal for emergency medications PRE-FILLED DISPOSABLE SYRINGES ADVANTAGES ease of administration reduction of medication error manufactured aseptically – ensured sterility commercially prepared – standardized labelling and stability information DISADVANTAGES usually single dose- no flexibility short expiry - 30 to 90 days or less if pharmacy prepared pharmacy prepared – cost to purchase compounder pharmacy prepared stability and contamination concerns covers losses due to dead space/ hub and needle allows exact quantity to be up to 10 % of the total what about narcotics and solution retention and vial delivered volume controlled drugs? closure solution trapping during withdrawal morphine lorazepam