Aseptic Technique and USP 797

1. Aseptic Technique and USP 797 • Definitions • Asepsis is the state of being free from the presence of pathogenic microorganisms. • Sepsis is the state of being contaminated by 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 is the procedure used to maintain an aseptic environment in which to compound sterile products CSP’s • Aseptic technique strives to maintain surgical asepsis. (meaning complete sterility and lack of endotoxin )

2. 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 (secondary engineering controls)

3. 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 3 components • Medium Risk CSP • Same as Low risk CSP but additionally • More than three components are a part of the IV admixture (i.e TPN’s) • CSP don’t contain antimicrobial preservative and product is given over more than 2 days • Complex preparation involved • High Risk CSP • Same as Low risk CSP but additionally • Compounding of manufactured ingredients that are non sterile and then performing terminal sterilization • Performing compounding in condition outside ISO5

4. Risk Levels and Expiration Dating • Low Risk CSP • In the absence of sterility testing • 48 hrs at room temperature • 14 days under refrigeration • 45 days frozen state • Medium Risk CSP • 30 hrs at room temperature • 7 days at refrigeration • 45 days at a frozen state • High Risk CSP • 24 hours at room temperature • 72 hours refrigerated • 45 days at a frozen state.

5. 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 50 ml SVP with 1 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

6. 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 100,000 particulates 0.1 micrometer or larger per cubic meter. By contrast, room air is classified as ISO9 which is no more than 1,000,000,000 particulates per cubic meter. (a ten thousand fold difference)

7. Anteroom • Usually consists of a storage area, an area for records, computers and printers, an buffer area for gowning • Has ISO class 8 standard (i.e 10X cleanner than normal room air) • 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.

8. Clean Room • The room where the LAFW hoods are located • Means same physical characteristics as anteroom • 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.

9. Maintaining of ante and Cleanrooms • Cleaning daily by shifts • Cleaning of all floor surfaces daily from the buffer area outwards, from the clean room out to anteroom. • Cleaning and disinfection of all shelving surfaces at least monthly • Documentation of such maintained

10. 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

11. Preparing to make an IV product • Enter the cleanroom with slow and deliberate movement. Remove jewelry and tie back loose hair. • Put on shoe coverings (booties) and then proceed to anteroom. • In anteroom, perform antiseptic washing of hands which includes washing hands and washing between fingers as well as using fingernail buffer pad to clean under the fingernails. Wash hands up to the elbows and rinse hands first allowing water to drip down to elbows. • Don surgical gown, hair cap, beard cover (if needed) and surgical mask if working with a hood with no front panel. • Gather syringes, needles, IV bags (with cover removed) • Perform second antiseptic handwash. • Donn powder free surgical latex gloves • Enter Buffer zone • Place all products into the laminar flow hood.

12. 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

13. 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

14. Remember, touch is the number one cause of product contamination. • Human skin harbors many organisms: Staphylococci, Streptococci, Actinobacter, Candida, Tricophyton Rubrum fungi, Pseudomonas, etc. • Contaminated IV products can cause bacteremia and fungemia, septic shock and death. • I will demonstrate aseptic technique in class with reference to drug manipulation.

15. The Finished products • If you are a pharmacy technicians that will be performing IV admixtures. Always leave the following item for the RPH to check: • All vials used in the process • All syringes used in the process drawn back to the volume you used. • All information recorded in the IV prep log book: Patient’s name, medical record number, drugs, concentrations, volumes used, lot number and manufacturer’s expiration. • Assigned a pharmacy expiration date (usually 24 hours at room temperature)

16. IV products continued • ALL Intravenous products must be clear to the eye. Cloudiness or discoloration could indicate a physical or chemical incompatibility. • Cloudiness indicates a drug has “come out” or precipitated out of solution. One example of this is mixing phenytoin sodium (Dilantin®) in D5W solution. A cloudy haze forms in the IV bag on standing. • A second example is in TPN, addition of calcium gluconate in a solution of high phosphate can cause calcium phosphate to “come out” of solution • A third example is excessive shaking and agitation of a solution of mannitol. Mannitol’s needle like crystals can be seen after such agitation.

17. 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.

18. Routes of IV administration • As mentioned before, the most common routes of IV administration are IV push, Primary IV infusion, and IV piggyback. • In IV push, the luer lok of a syringe is attached directly to the patient’s intravenous access and slowly “pushed” in by pressing on the syringe barrel. It may also by given through a Y site on a primary IV line with a fluid running IV solution. • Primary IV infusion, the drug admixture is a large volume parenteral IV bag that is run through a dedicated IV line. • In IV piggyback, the drug admixture is a small volume parenteral that is infusion through a secondary line into a primary one through a Y site connection.

19. Other Parenteral routes • Epidural routes are IV catheters that are tunneled into a patient’s back near the spinal cord of the patient. Meant to deliver opiates and other pain medications to post op patients and obstetric patients. Solutions made for epidural use must be made from preservative free drug products. • Intrathecal injections are made into the spinal cord. The needle passes through the dura mater into the subarachnoid space. This method is used to administer spinal opiates at doses far below regular IV doses. It is also used to deliver chemotherapy with methothexate and in the delivery of a drug called baclofen to patients with severe cerebral palsy. • Some drugs given this way can be fatal. An example is the drug Vincristine.