Section B - Sterile Products I. Definitions

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Section B - Sterile ProductsI. Definitions

• A. Sterile products
• B. Sterility
• C. Aseptic technique
• D. Parenteral preparations
• E. Pyrogens
• F. pH
• G. Tonicity
• Isotonic, Hypertonic and Hypotonic solutions
• Isoosmotic, Hyperosmotic and Hypoosmotic
  solutions

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Section B - Sterile Products II A. STERILE
PRODUCT PREPARATION AREAS

• Controlled Area - Usually Class 10,000 or 100,000
  room
• Critical Area - Usually Hood area Class 100 for
  Rx
• 1. High-efficiency particulate air (HEPA)
  filters
• a. HEPA filters remove all airborne
  particles sized 0.3 µm or larger with an
  efficiency of 99.97.
  
  b. In addition, HEPA-filtered rooms generally are
  classified as
  Federal Class 100,
  1000, 10,000 and 100,000
• (A class 100 has no more than 100 particles of
  0.5 ?m or larger/cubic ft.)
• 2. Positive-pressure air flow
• 3. Counters in the clean room
• 4. Walls and floors
• 5. The uniform velocity of the air flow is 90
  ft/min 20

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Section B - Sterile ProductsII B. Laminar flow
hoods

• Requirements
• a. Laminar flow hoods utilize HEPA filters
• b. Rx Hoods are classified as Federal Class 100
  (class 100 hoods contain no more than 100
  particles sized
  0.5 µm or larger per cubic foot of air)
• Types
• Horizontal laminar flow hoods
• Vertical laminar flow hoods
• Inspection and Certification
• at least every 6 to 12 months

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Section B - Sterile Products
III. STERILIZATION METHODS AND EQUIPMENT

• A. Thermal sterilization
• use of either moist or dry heat
• 1. Moist heat sterilization - an autoclave
• 121?C, at15 lb. pressure for at least 15
  minutes
• 2. Dry heat sterilization - an oven
• at least 160?C for 120 minutes
• B. Gas sterilization - ethylene oxide
  air, moisture and heat - Quarantine
  period
• C. Radiation sterilization - ionizing radiation
  - gamma rays

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III. STERILIZATION METHODS AND EQUIPMENT D.
Mechanical sterilization (filtration)

• Removes(but does not destroy) micro-organisms and
  clarifies solutions by eliminating particulate
  matter. For solutions rendered unstable by
  thermal, chemical, or radiation sterilization,
  filtration is the preferred method.
  
• 1. Depth filters usually consist of fritted glass
  or unglazed porcelain--substances that
  trap particles in channels.
• 2. Screen (membrane) filters are films measuring
• 1 to 200 µm thick made of cellulose esters,
  microfilaments, polycarbonate, synthetic
  polymers, silver, or stainless steel.

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III. STERILIZATION METHODS AND EQUIPMENT D.
Mechanical sterilization (filtration)

• 2. Screen (membrane) filters
• Screen Filters are
• a. A meshwork of millions of microcapillary
  pores of identical size filter the solution
• by a process of physical sieving.
• b. Because pores make up 70 to 85 of the
  surface, screen filters have a higher
• flow rate than depth filters.
• c. Screen filters come in three basic types.

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III. STERILIZATION METHODS AND EQUIPMENT D.
Mechanical sterilization (filtration) THREE
TYPES OF SCREEN FILTERS

• Particulate filters remove particulates of glass,
  plastic, rubber, and other contaminants. The pore
  size of standard particulate filters ranges from
  0.45 to 5 µm. (special sizes for blood fat
  emulsions)
• Microbial filters, with a pore size of 0.22 µm or
  smaller, ensure complete microbial removal or
  sterilization.
• Final filters, which may be either particulate or
  microbial, are in-line filters used to remove
  particulates or micro-organisms from an
  intravenous (IV) solution before infusion.

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Section B - Sterile Products IV. PACKAGING OF
PARENTERAL PRODUCTS

• Parenteral preparations and other sterile
  products must be packaged in a way that maintains
  product sterility until time of use and prevents
  contamination of contents during opening.
• Types of containers
• Ampoules the oldest type of parenteral product
  containers, are made entirely of glass.
  Intended for single use only
• Vials are glass or plastic containers closed
  with a rubber stopper and sealed with an
  aluminum crimp.
• Advantages and Disadvantages
• of these containers

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IV. PACKAGING OF PARENTERAL PRODUCTS Advantages
and DisadvantagesVials and Ampoules

• Advantages over ampoules
• 1. They can be designed to hold multiple doses
• 2. It is easier to remove the product.
• 3. They eliminate the risk of glass particle
  contamination during opening.
• Disadvantages over ampoules
• 1. The rubber stopper may become cored.
• 2. Multiple withdrawals may result in
  contamination.
• 3. Stability - Reaction with rubber and plastic

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IV. PACKAGING OF PARENTERAL PRODUCTS Prefilled
Containers

• Prefilled syringes - (e.g., Abboject, Bristoject)
  Drugs administered in an emergency (e.g.,
  epinephrine, atropine, ) are available for
  immediate injection.
• Prefilled cartridges - (e.g., Tubex, Carpuject)
  Ready-to-use parenteral packages with a needle
  that requires a metal or plastic cartridge
  holder.
• Infusion solutions - two categories small
  volume parenterals (SVP), those having a volume
  less than 100 ml(in practice 100 ml or less)
  large volume parenterals (LVP), those having a
  volume of 100 ml or greater. (in practice gt100
  ml)

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IV. PACKAGING OF PARENTERAL PRODUCTS Packaging
materials

• Glass and plastic polymers
• Glass, the original parenteral packaging
  material. Glass is Silicon dioxide(sand) with
  metallic oxide. Boron oxide, earth alkaline
  oxides(Ca, Na, K etc.) and metal oxides for color
  - manganese for amber.
• Type I. Borosilicate glass - most resistant and
  least reactive - sterilize either before or
  after.
• Type II. Soda-Lime glass - treated with acid gas
  - must sterilize before by dry heat
• Type III. Soda-Lime glass - least used - must
  sterilize before.

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IV. PACKAGING OF PARENTERAL PRODUCTS Plastic
polymers

• Plastics - Polyvinylchloride (PVC) and Polyolefin
• PVC is flexible and non-rigid
• Polyolefin is semi-rigid and can be stored
  upright
• Chemicals added to plastic containers
• Stabilizers - protect from light and
  discoloration
• Accelerators - increases rate of polymerization
• Antioxidants - retard oxidation
• Fillers - modify physical properties
• Lubricants - to ease molding
• Colorants - add color

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IV. PACKAGING OF PARENTERAL PRODUCTS Rubber
Closures Composition

• Rubber (natural) neoprene or butyl base polymer
• Vulcanizing agents - sulfur - reduces plasticity,
  resist temp changes.
• Accelerators - sulfides/guanidine - increase
  vulcanization rate
• Activators - zinc oxide - activate accelerators
• Fillers - carbon black/kaolin - strength and
  hardness
• Plasticizers - dibutyl phathalate - flexibility
• Antioxidants - aromatic amines - retard oxidation

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V. PARENTERAL ADMINISTRATION ROUTES

• Site volume in ml
  needle type
• Intradermal-------- 0.1 ml ---------24 -25 G, 1/4
  - 5/8?
• Subcutaneous----1.0 ml ---------15 -25 G, 1/4 -
  5/8?
• Intramuscular ---- 2.0 ml (5 max)---- 19 - 22 G,
  1 - 2?
• Intravenous ------ no limit -----------15 - 25 G,
  1 - 2?
• Intra-arterial ----- no limit ---------- 15 - 25
  G, 1 - 2?
• Intracardiac ------ 10 ml (50 max ) ----18 - 21
  G, 3 1/2?
• Intraperitoneal -- ------14 G, 4 - 6?
• Intraspinal -- ------20 - 22G, 3 - 5?
• Intrathorasic ----- 13 G, 5 - 6?

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VI. NEEDLES and SYRINGES Hypodermic needles
are stainless steel or aluminum devices that
penetrate the skin for the purpose of
administering or transferring a parenteral
product.

• Needle gauge refers to the outside diameter of
  the needle shaft the larger the number, the
  smaller the diameter
• Needle lengths range from 1/4 to 6 inches.
  Choice of needle length depends on the desired
  penetration
• Bevels are slanting edges cut into needle tips to
  facilitate injection through tissue or rubber
  vial closures. a. Regular-bevel needles are the
  most commonly used type suitable for SQ and IM
  injections b. Short-bevel needles are used
  when only shallow penetration is required (as
  in IV injections). c. Intradermal-bevel needles
  are designed for ID injections

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VI. NEEDLES and SYRINGES Syringes are devices
for injecting, withdrawing, or instilling fluids.
Made of reusable glass and plastic

• Syringe volumes range from 0.3 to 60 mL.
• Syringe Parts 1. a glass or plastic barrel 2. a
  tight-fitting plunger at one end 3. a small
  opening at the other end accommodates the head of
  a needle.
• Calibrations metric or English system, vary in
  specificity depending on syringe size the
  smaller the syringe, the more specific the
  scale.Insulin syringes have unit gradations (40
  or 100 units/m) rather than volume gradations.
• Syringe tips come in several types.Luer-Lok tips
  are threaded to ensure that the needle fits
  tightly in the syringe. Luer-Slip tips are
  unthreaded. Needle is held by friction and is not
  lock into place.
• Eccentric tips, set off center, allow the needle
  to remain parallel to the injection
  site.Catheter tips are used for wound irrigation
  and administration of enteral feedings. Not
  intended for injection.

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VII. PARENTERAL DRUG DELIVERY

• A. Injection sites
• 1. Peripheral vein injection is preferred for
  drugs that do not irritate the veins and for
  short-term IV therapy. Generally, the dorsal
  forearm surface is chosen for venipuncture.
• 2. Central vein injection is preferred for
  administration of irritating drugs or
  hypertonic solutions for long-term IV therapy,
  and when a peripheral line cannot be maintained.
  Large veins in the thoracic cavity, such as the
  subclavian, are used.
• B. Infusion methods
• 1. Continuous drip infusion is the slow,
  primary-line infusion. Provide fluid and
  electrolyte replacement.
• 2. Intermittent infusion allows drug
  administration at specific intervals. Four
  different techniques may be used.

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VII. PARENTERAL DRUG DELIVERY Intermittent
Infusion Techniques

• a. Direct (bolus) injection - delivers small
  volumes of a drug.
• b. Additive set infusion - use of a
  volume-control device for delivery of small
  amounts of IV solutions or diluted medications.
  The fluid chamber is attached to an independent
  fluid supply or placed directly under the
  established primary IV line.
• c. Piggyback method - A special coupling method
  for the primary IV tubing permitting the infusion
  of a piggyback drug solution.
• d. intermittent infusion injection devices -
  Also called scalp-vein, heparin-lock, or
  butterfly infusion sets, these devices permit
  intermittent delivery while eliminating the need
  for multiple venipunctures or prolonged venous
  access with a continuous infusion.A heparin flush
  set must be used to maintain the line.(Set 1 ml
  NS - 0.5 ml Heparin - 1 ml NS)

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VII. PARENTERAL DRUG DELIVERY Pumps and
ControllersPumps and controllers are used to
administer parenteral infusions with accuracy and
safety.

• Pumps - Electronic devices, Piston-cylinder
  Peristaltic Mechanisms.
• Controllers, unlike pumps, exert no pumping
  pressure on the fluid. The infusion is by
  gravity and the controller counts the infusion
  drops electronically
• Types of pumps and controllers
• a. Volumetric pumps and controllers. Combination
  is most
• commonly used for both intermittent and
  continuous infusions..
• b. Syringe pumps.- Selective use - in pain
  management and pediatrics
• c. Mobile infusion pump - small infusion devices
  designed for ambulatory and home healthcare
  patients.
• d. Implantable devices - infusion devices
  surgically placed under the skin to provide a
  continuous release of medication.

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VIII. PARENTERAL PREPARATIONS

• Primary Parenteral Fluids
• For preparation and administration of parenteral
  products
• Sterile Water For Injection (SWFI) - For
  preparation only
• Bacteriostatic Water For Injection (BWFI) - For
  preparation only
• Normal Saline Solution (NS) - For both
  (preparation administration)
• Dextrose 5 in Water (D5W) - For both
  (preparation administration)
• Ringers Solution (R) - For administration only
• Lactated Ringers Solution (LR) - For
  administration only
• Combination Parenteral Fluids
• D5/NS, D5/1/2 NS, D5/1/4 NS and D2.5/1/2 NS
• D5/R, D5/LR

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Parenteral Antineoplasic PreparationsSpecial
Training Required

• Special Documented Training
• Proper handling, preparation, administration,
  disposal
• and spill cleaning training of highly toxic
  drugs.
• Garments - use gown, shoe cover, mask, gloves,
  hair cover and
• goggles as specified. Proper attire is required
  for these drugs.
• Handling - record and check all drug containers.
• Preparation - only in vertical laminar flow hood.
• Must use spill mats in hood. Use either chemo
  spike or negative pressure during preparation.
• Administration - infusion set, if needed, must be
  primed in the hood.
• Disposal - dispose all material in special
  containers.
• Spill Cleaning - must follow team training
  procedures.

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IX. PARENTERAL INCOMPATIBILITIES

• Types of Incompatibilities
• 1. Physical incompatibility - visible change in
  solution appearance.
• 2. Chemical incompatibility - chemical change
  resulting in either toxicity or therapeutic
  inactivity which is not always visible.
• Chemical Changes occur due to
• Complexation, Oxidation, Reduction, Photolysis
• 3. Therapeutic incompatibility - Change in
  activity of one with others.
• Factors affecting IV compatibility
• pH , Temperature, Time, Dilution, Mixing order
• Preventing or minimizing incompatibilities
• Practical Control of all factors which lead to
  incompatibilities

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X. QUALITY CONTROL AND QUALITY ASSURANCE

• Definitions
• Quality control is the day-to-day assessment of
  all operations including analytic testing of the
  finished product.
• Quality assurance, an oversight function,
  involves the auditing of quality control
  procedures and systems, with changes as needed.
• USP Tests
• Sterility Test - Microbial Growth Promotion
  Test.
• Pyrogen Test - Rabbit Temperature Test.
• Endotoxin Test - LAL(Limulus Amebocyte Lysate)
  Test.
• Particulate Test - Microscopic Particle Count
  Test.

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Sterile Product Section B
END