Aseptic Technique and USP 797 Definitions Asepsis is the state of being free from the presence of pathogenic microorganisms. Septicemia is the presence of microorganisms in the blood Septic shock is the condition of overwhelming infection of the blood by septicemia. Aseptic technique strives to maintain surgical asepsis. (meaning complete sterility and lack of endotoxin )

USP 797 rules United States Pharmacopeia 797 chapter on compounding of sterile products (CSP) was published in the 27th revision to USP on January 1st, 2004 USP 797 is applicable to all facilities where compounded sterile products (CSP) are made, stored and sent to the patient USP 797 applies to the aseptic technique used to make CSPs as well as the environment in which it is done

Microbial Risk Levels in USP 797 Low risk CSP Made under ISO5 conditions Involves aseptic transfer of manufacturer based sterile products using sterile equipment (i.e Needles and syringes) to compound IV admixtures. Does not involve open systems and no more than 2 additives to one system No more than 48 hours between preparation and administration at room temp Medium Risk CSP More than two additives are a part of the IV admixture (i.e TPN’s) Complex preparation involved No more than 30 hours between preparation and administration at room temp High Risk CSP Compounding of manufactured ingredients that are non sterile and then performing terminal sterilization Performing compounding in conditions outside ISO5 24 hours at room temperature

Hospital Compounding For the most part you may be preparing only low or medium risk CSP’s Example of a low risk CSP Making a 250 ml SVP with 1.25 gram of vancomycin under ISO5 conditions Example of a medium risk CSP Compound a triple mix TPN with additional additives of insulin, multiple vitamin injections, and other electrolytes Example of high risk CSP Compounding a sterile ophthalmic solution from a manufactured product that is not sterile and passing solution through a 0.22 micron filter several times

Air Quality and Cleanness ISO stands for international organization for standardization ISO was formed in 1947 in Geneva Switzerland Provides different levels of air quality cleanness ISO 5 means no more than 100 particulates that are 0.5 micrometer or larger per cubic foot of air. By contrast, room air is classified as ISO9 which is no more than 100,000 particulates per cubic foot. (thousand fold difference)

Anteroom Usually consists of a storage area, an area for records, computers and printers, an buffer area for gowning Has a sink equipped with surgical scrub soap (Chlorhexidine), and has handfree or pedal activated water systems Has the following characteristics: Smooth walls with panels locked and sealed Vinyl covered floor with seals heated together Joints and junctures between walls and ceilings must be chauked with no visible cracks.

Clean Room The room where the LAFW hoods are located Means same physical characteristics as anteroom Has ISO class 8 standard No sinks and floor drains If facility only compounds low and/or medium risk CSPs the clean and ante rooms need not be separated. Area immediately next to LAFW hoods is called buffer area If all risk levels are compounded clean and ante rooms must be separated. Must be maintained as a positive room air pressure environment if separated.

Structure of USP 797 defined Cleanroom REST OF THE PHARMACY Cleanroom: Positively pressured, Houses BSC Vinyl flooring ISO 8 environment Negatively pressured for chemo or hazardous drugs Anteroom Vinyl flooring Maybe ISO 8 environment Contains sink for hand hygiene Gowning apparel

Maintaining of ante and Cleanrooms Cleaning requirement BSC or LAFW = beginning of shift, before each preparation, 30 minutes into the procedure, when surface is visible contaminated Cleaning of all floor surfaces daily from the buffer area outwards, from the clean room out to anteroom. Countertops: daily Cleaning and disinfection of all shelving surfaces at least monthly Walls, Ceilings: monthly Documentation of such maintained Cleaning solvent required by USP for ISO5 and countertops: Isopropyl Alcohol USP 70%

Laminar Air Flow Hoods and Workbenchs LAFH and workbenchs are designed to blow parallel sheets of sterilized clean air over a work surface The hood is usually washed and disinfected with 70% isopropranol by a pharmacist at the beginning and end of the shift. Washing is from top to bottom of the hood and back to front in the direction of laminar flow. HEPA filters remove over 99% of particles, including microorganism 0.3 microns or larger. When cleaning the HEPA filter grill do not spray the filter always spray the sterile gauze pads and clean the surface of the grill If the HEPA Laminar flow hood is turn off for any reason then it must be turn on for at least 30 minutes before commencing any IV preparation. Horizontal Laminar Flow Hood: the HEPA filter is at the back of the hood and blows laminar air towards the operator Vertical Laminar Flow Hoods: the HEPA filter is on the top of the hood and laminar air flow sheets are blown to the work surface and not to the operator Also called a biological safety cabinet Must be recertified every 6 months

Biological Safety Cabinets Class I open system that draws air from the cleanroom Class II air is recirculated through vents in the front and back and passed though a HEPA filter on the top of the cabinet back down to the worksurfaces. Four types A, B1, B2, and B3 Type A is not vented to the outside Type B1,B2,B3 all provide some or all exhaust to the facility’s external vent system. Class III are completely enclosed system under negative pressure which are vented. Manipulation by the operator are with a gloved apparatus through the front of the cabinet

Biological Safety Cabinets

Preparing to make an IV product Enter the antiroom with slow and deliberate movement. Remove jewelry and tie back loose hair. PPE (Personal Protective Equipment) Procedure Order Put on shoe coverings (booties) Put on head cap Put on lint free surgical mask Wash hands up to the elbows for 30 seconds and rinse hands first allowing water to drip down to elbows Don lint free surgical coverall (Bunnysuit) Don powder free sterile latex gloves Enter cleanroom

When in the cleanroom Before placing the drug product, IV bag, etc in the BSC Clean the BSC From top to bottom From the inside outside direction Clean with 70% isopropyl alcohol Clean the surface of all IV vials, IV bags with 70% isopropyl alcohol Sterilize gloves or replace

Remove all caps to vials Remove all caps to vials. Swab each vial with alcohol swab from back to front once with swab. Swab medication port of the IV bag that you will use. All products should be 6 inches inside the hood. Arrange materials in such as way as to not block any of the laminar flow air currents. Once inside the hood, your hands should not leave the inside of the hood. If they do you will need to sanitize your gloves before returning to the hood area. Always remember not to touch critical areas

The following are critical areas which must not be touched. All parts of the needle. The hub of a luer lok syringe The ribs of the piston of the syringe. The injection port of the IV bag. The rubber entry port of the vial

Common causes of physical and chemical incompatibilities are: A great reference to use to determine drug-drug, drug-IV solution compatibilities is a book called, Trissel’s Handbook on Injectable Drugs® Common causes of physical and chemical incompatibilities are: Drugs mixed in low pH solutions, like D5W Drugs mixed in hypertonic solutions, like D5WNS Drugs mixed in incorrect IV mediums. Such drugs are not compatibility in the PVC container of an IV bags; these drug are mixed in glass IV containers. A class example is nitroglycerin which is used for patients with acute MI. Drugs mixed with other drugs that “complex” each other.

Total Parenteral Nutrition Used to deliver nutrition to patients who can not have enteral nutrition Some times called a triple mix Components 10% amino acids 50% dextrose 10% or 20% fats (lipids) Additives Magnesium sulfate, Calcium Gluconate, Potassium Phosphates, Sodium chlorides, Zinc, MVI Sometimes, Insulin is added When fat is present in this IV requires use of an IV set with an in line filter Usually given to patients over 24 hours and in a dedicated line; mixing with other drugs, not recommended

Type of Parenteral Products Injections are products that are already mixed into solutions. Solutions are pH buffered, sterile, pyrogen free with methylparabens, benzyl alcohol preservatives Packaged in Vials Ampules Single doses Vials Have no preservatives Once open, use and discard Multiple Doses Vials Have preservatives Once open 28 days exp Courtesy of :http://www.hospira.com/en/products_and_services/drugs/FENTANYL_CITRATE

Type of Parenteral Products For Injections : products that are lyophilized powders that require addition of water to form a solution a given concentration. Usually these products are single dose Courtesy of :http://www.hospira.com/en/products_and_services/drugs/CEFTRIAXONE

IV Labeling Labeling rules are governed by the state, non governmental agencies guidelines (JCAOH, USP797) Include the following: Patient’s name, location in institution, MRN Drug and strength Base fluid Name of other additives and quantities of The intended time of administration of drug Rate of administration if LVP (or hang time if SVP) Prep by field and Verified by field Product expiration field In addition a nursing label may be attached detailing: When product was “hung” (i.e. started) By whom the product was hung

LaGuardia College Hospital Sample IV Label LaGuardia College Hospital 32 Thomson Ave Long Island City, N.Y 11345 Name: John Doe MRN: 1234567 Location: CICU Bed: 2 Amiodarone 450 mg In: D5W 250 ml Continuous Infusion Administration time: 03/15/2015 19:00 Rate of Infusion: 33 ml/hr Prep by:____ Verified by:______ Expiration : 03/16/15 18:00

LaGuardia College Hospital Sample IV Label II LaGuardia College Hospital 32 Thomson Ave Long Island City, N.Y 11345 Name: John Doe MRN: 1234567 Location: CICU Bed: 2 Ceftriaxone 1,000 mg In: D5W 50 ml IVPB Administration time: 03/15/2015 19:00 Hang Time: 15 minutes Prep by:____ Verified by:______ Expiration : 03/16/15 18:00

Parenteral Therapy Intravenous Therapy (IV) involves injecting a medication directly into the blood via venous access devices IV products must be sterile and pyrogen free with no particulate matter in the solution Intramuscular Injection (IM) involves injection into the large belly of a muscle Subcutaneous Injection (SubQ) involves injection in the hypodermis of the skin Epidural Injection involves injection next to the dura mater of the spinal cord Intrathecal Injection involves injection into the subarchnoid space of the meninges Intrathecal Baclofen in cerebral palsy patients

Epidural Injection Courtesy of: http://richardspatafora.com/2011/05/19/lumbar-epidural-cortisone-injection/

ALL THESE PRODUCTS MUST BE STERILE AND PYROGEN FREE IN ADDITION EPIDURAL AND INTRATHECAL INJECTION MUST BE PRESERVATIVE FREE IN ADDITION TO STERILITY Preservative free is required for epidural injections Coutesy of: http://www.drugs.com/pro/duramorph.html

Type of IV Therapy IVP or Intravenous push involves insert a needle and syringe directly in a VAD (vascular access device) IV Infusion Large Volume Parenteral involves a large volume of fluid given IV over a long period of time (1,000 ml) Often called a “drip” with given continuously SVP or a small volume parenteral is a small volume of fluid (50 ml to 100 ml) given IV over a short period of time (10 minutes or so) Often called an intermittent infusion IVPB, intravenous piggyback is a type of SVP that is infused along with a LVP

Source: wikimedia commons page

Primary IV Infusion Sets These infusion sets are made of PVC and DHEP and meant to carry the fluid from an IV bag to the hub of a IV catheter This tube consists of a piercing pin, drip chamber, an in line filter and several Y site IV ports for the administration of the secondary IV fluids through a piggyback system Used to deliver a LVP over several hours

Secondary IV administration sets Secondary IV administration sets are used to deliver smaller volumes of drug containing fluids of about 50-100 ml In general this tube has a piercing pin, drip chamber, and a roller clamp and male luerlok. In general this tubing has no Y site ports The connection is attached to the Y site of a primary line

INFUSION SET UP http://www.youtube.com/watch?v=N0rCuC2XE1U 1 liter of NS or D5W Addition port Administration set port Drip chamber http://www.youtube.com/watch?v=N0rCuC2XE1U

Intravenous Solutions and tonicity IV solutions that are “isotonic” to plasma have the same tonicity as plasma (300 mOsmoles/L) and cause no shift in body fluid compartments 0.9 % Na CL is “normal saline” and has a tonicity of 300 mOsmoles/L Vascular Compartment Interstitial Compartment (fluid around organs)

Intravenous Solutions and tonicity IV solutions that are “hypertonic” to plasma have the higher tonicity than plasma and cause a shift in body fluid compartments from the Interstitial space to the vascular compartment causing this compartment to become volume over loaded with heart failure and increase pressure on the brain 3% NaCl (1000 mOsmole/L) 14% NaCL (5,000 mOsmole/L) 23.4 % NaCL (8,000 mOsmole/L) Vascular Compartment Interstitial Compartment (fluid around organs)

Intravenous Solutions Normal saline (0.9%) is one of the most common because its isotonic with plasma. Isotonic means equal to it in terms of “tonicity”. i.e. plasma has a tonicity valve of about 290 mOsm. Normal saline or NS is about 300 mOsm. Tonicity of a solution determines if bodily fluid shifts will occur Dextrose 5% in water (D5W) is the second most common type. Consists of glucose or dextrose in water to make it 285 mOsm (isotonic) D5WNS is a combination of the two and is used when some calories in the form of glucose is needed. Hypertonic (580 mOsm about) but it is Ok to use. 3 % Saline (NaCL) is only used to treat certain brain conditions. Very hypertonic and can cause death if used improperly 23.4% saline (NaCL) used only in certain rare conditions and in small volumes. Will cause death if used improperly (remember Emily Jerry?)