Aseptic Technique, Sterile Compounding: Intravenous and Admixture

1. Aseptic Technique, Sterile Compounding:Intravenous and Admixture Lecture #1 IV PREPARATION COURSE

2. Aseptic Technique “Aseptic technique is the term used for all procedures and techniques performed to keep a sterile product from becoming contaminated.”

3. Parenteral Drug Administration • Basic Intravenous Therapy - Intravenous (IV) route of administrations is the most common route that parenteral dose are administered today. - Other parenteral dosage forms are: 1. intramuscular (IM) 2. subcutaneous (SubQ) 3. intradermal (ID) 4. epidural - IV fluid is in a large-volume parenteral (LVP), usually more than 100 mL

4. Basic IV Therapy cont… - Hang on an IV pole approximately 36 inches higher than the patient’s bed. - The LVP is usually a simple solution of dilute dextrose, sodium chloride or both. - Solution is infused continually to keep blood from clotting in the catheter and plugging the line.

5. Basic IV Therapy cont… - Primary IV set – attaches to the LVP. Most IV sets that flow by the force of gravity have several common features: 1. Drip chambers are typically classified as macrodrip or minidrip based on the size of the drop that is formed in the drip chamber. a. Macrodrip – deliver 10 to 20 drops/mL b. Minidrop or Microdrip – deliver 60 drops/mL 2. Electronic infusion devices are usually used in fluid restricted patients or when the LVP contains a drug that must be administered at a precise rate that cannot be monitored by using the gravity method.

6. Continued… - Secondary IV sets – drugs that are routinely delivered through the same basic IV setup are usually attached to a “secondary IV set” connected to the primary set. - Catheters – typically inserted into a peripheral vein (arm, leg, or hand) or a central vein (in the chest near the heart). 1. Where the catheter is inserted depends on the contents of the IV 2. Peripheral insertion is more common than central insertion 3. The central catheter is more complicated and riskier to insert and maintain, but has fewer restrictions with respect to type and rate of administration

7. Continued… 4. Types of peripheral catheters: a. Plastic – most common b. Steel – commonly referred to as a scalp vein or butterfly. Used in patients that require IV therapy who are still capable of eating and drinking, do not require supplemental fluids, and might be ambulatory. 5. Central catheters can be temporary; used for days or weeks (such as during a hospital stay) or permanent, when used for months or years (such as home care or cancer patients)

8. Continued… 6. The central catheter gives direct access into a vein that that has a high flow of blood. 7. Peripheral inserted central catheter (PICC) offers some of the benefits of both central and peripheral catheters. Inserted peripherally it is a long flexible catheter that travels through the vein and its tip ends near the heart where there is a high volume of blood flow.

9. Risks of Intravenous Therapy • Infection – results if a product contaminated with bacteria is infused into a patient. - human touch contamination continues to be the most common source of IV related contamination. • Air embolus – incidence is low, because many solutions are administered using infusion pumps equipped with an alarm that sound when air is in the IV line. These are called air-in-line alarms. - in adults it takes 150 or 200 mL of air (much less in infants or pediatric patient) given quickly to result in harm.

10. Risks continued… • Bleeding – when the IV catheter is removed, bleeding may occur around the catheter site. • Allergic reaction – when a patient has an allergic reaction to a substance given parenterally the reaction is usually more severe than if the same substance was given by another route (e.g. mouth, topically, or rectally) - one reason for this is that substances given parenterally cannot be retrieved like substances given by other routes. • Incompatibilities – if an incompatibility exists, the drug might precipitate, be inactivated, or adhere to the container. Incompatible solutions should not be administered to patients.

11. Risks continued… • Extravasation – occurs when the catheter punctures and exits the vein under the skin, causing drugs to infuse or infiltrate into the tissue. • Particulate matter – refers to particles present in parenteral products. When injected into the bloodstream can cause adverse effects to the patient. Examples: - microscopic glass fragments - hair - lint or cotton fibers - cardboard fragments - undissolved drug particles - fragments of rubber stoppers

12. Risks continued… • Pyrogens – the by-products or remnants of bacteria, can cause reactions (e.g. fever and chills) if injected in large enough amounts. • Phlebitis – Irritation of the vein. Caused by: - the drug being administered (due to it chemical properties or its concentration) - the location of the IV site - a fast rate of administration - the presence of particulate matter - the patient usually feels pain or discomfort along the path of the vein (often severe) and red streaking may also occur

13. Aseptic Preparation of Parenteral Products • Aseptic Technique - Programs designed to ensure the aseptic preparation of sterile products. - The main elements these programs focus on are: 1. the development and maintenance of good aseptic technique in the personnel who prepare and administer sterile products. 2. Development and maintenance of a sterile compounding are complete with sterilized equipment and supplies. 3. Development and maintenance of the skills needed to properly use a laminar flood hood (LAH).

14. Aseptic Technique continued… • Aseptic technique is a means of manipulating sterile products without contaminating them. • Proper use of a LAH and strict aseptic technique are the most important factors in preventing the contamination of sterile products.

15. Sterile Compounding Area • Sterile parenteral solutions must be free of living microorganisms and relatively free of particles and pyrogens. • A sterile compounding area should be cleaned daily and segregated from normal pharmacy operations, patient specimens, nonessential equipment, and other materials that produce particles. Examples: - cardboard into the clean environment should be avoided. - traffic flow should be minimized. - floors should be disinfected periodically. - trash should be removed frequently and regularly.

16. Compounding Area continued… • Sterile products should be prepared in a Class 100 environment, which contains no more than 100 particles per cubic foot that are 0.5 micron or larger in size. • LAHs are frequently used to achieve a Class 100 environment.

17. Laminar Airflow Hoods (LAH) • Underlying principle of LAHs is that twice-filtered layers of aseptic air continuously sweep the work area inside the hood to prevent the entry of contaminated room air. • Two common types: - Horizontal LAH – sweeps filtered air from the back of the hood to the front. 1. use an electrical blower to draw contaminated room air through a prefilter. 2. The prefilter, which is similar to a furnace filter, only removes gross contaminants and needs to be cleaned or replaced on a regular basis. 3. The high efficiency particulate air or (HEPA)filter removes 99.9% of particles that are 0.3 micron or larger.

18. Laminar Airflow Hoods continued… • Vertical LAH – HEPA filtered air emerges from the top and passes downward through the work area. - used for antineoplastic (anticancer) drugs. - the risk of exposure to airborne drug particulates is minimized. - the type of vertical LAH used for the preparation of antioneoplastics contains airflow within the hood and are referred to as biological safety cabinets (BSCs). • The critical principle of using LAHs is that nothing interrupts the flow of air between the HEPA filter and the sterile object. The space between the HEPA filter and the sterile object is known as the critical area.

19. Hoods continued… • To maintain sterility, nothing should pass behind a sterile object in a horizontal flow hood or above a sterile object in a vertical flow hood. • Materials placed within the laminar flow hood disturb the patterned flow of air blowing from the HEPA filter. This “zone of turbulence” created behind an object could potentially extend outside the hood pulling or allowing contaminated room air into the aseptic working area. • It is advisable to work with objects at least six inches from the sides and front edge of the hood without blocking air vents, so that unobstructed airflow is maintained between the HEPA filter and sterile objects.

20. Hoods continued… • The following are general principles for operating LAHs properly: - A LAH should be positioned away from excess traffic, doors, air vents, or anything that could produce air currents. - If turned off, it should be allowed to run for 15-30 minutes before use. - Before use, all interior working surfaces of the laminar flow hood should be cleaned with 70% isopropyl alcohol or other appropriated disinfecting agent and a clean, lint-free cloth. Cleaning should be performed from the HEPA filter toward the front of the LAH (in a horizontal LAH) so that contaminants are moved out of the hood.

21. Hood Criteria continued… • Nothing should be permitted to come in contact with the HEPA filter. This includes cleaning solution, aspirate from syringes, or glass from ampules. Ampules should not be opened directly toward the filter. • Do not put paper, pens, labels, or trays into the hood. • Jewelry should not be worn on the hands or wrists when working in the LAH since it may introduce bacteria or particles into the clean work area. • Actions such as talking and coughing should be directed away from the LAH working area, and any unnecessary motion within the hood should be avoided to minimize the turbulence of air flow.

22. Hood Criteria continued… • Smoking, eating or drinking are prohibited in the aseptic environment. • All aseptic manipulations should be performed at least six inches within the hood to prevent the possibility of potential contamination caused by the closeness of the worker’s body and backwash contamination resulting from turbulent air patterns developing where LAH air meets room air. • LAHs should be tested by qualified personnel every six months, whenever the hood is moved, or if filter damage is suspected.

23. Personal Attire • The first component of good aseptic technique is proper personal attire. • Clean garments, which are relatively particulate free, should be worn when preparing sterile products. • Many facilities provide clean scrub suits or gowns for this purpose. • Hair covers and shoe covers help reduce particulate or bacterial contamination, and some experts claim that the use of surgical masks and gloves is warranted as well.

24. USP 797 – New Standards • The primary structure of the new USP standards is based on 3 risk levels classified according to the potential for: - Microbial contamination (microorganisms and endotoxins) - Physical contamination (particulate contaminants: from cotton garments, cardboard cartons, pencils, paper towels, chewing gum and electronic equipment) - Chemical contamination (solid or liquid matter from precipitates)

25. Standards continued… • There are specific standards for each risk level. • Standards regarding personnel training, environmental quality and control, verification of compounding accuracy, packing and transport, adverse event reporting, storage, and beyond-use dating.

26. Risk Levels: Low Risk • Definition: - All aseptic manipulations within class 100 environment using only sterile ingredients and devices - Only single transfers used - Measuring/mixing no more than 3 products • Examples: - Single patient doses - Single patient syringe w/o additives - Batch syringes with preservatives - Sterile solution withdrawn from an amp and filtered to remove glass particles - Manually prepared TPN with three ingredients

27. Risk Levels: Medium Risk • Definition: - No Broad Spectrum antibacterial present despite administration over several days - Complex aseptic manipulations - Multiple doses in one container for multiple patients or one patient on multiple occasions • Examples: - Batch reconstituted antibiotics without preservatives - Batch syringes w/o preservative - Filling reservoirs with multiple sterile products and evacuating air for administration over several days at room temperature - TPN prepared by a compounder

28. Risk Levels: High Risk • Definition: - Sterile products compounded from nonsterile ingredients or use of a nonsterile device prior to terminal sterilization - Sterile ingredients, components, or devices exposed to air quality < class 100 if opened or partially used and not adequately preserved • Examples: - Mixing or measuring in nonsterile devices - Assuming 95% purity of ingredients - Injections made from nonsterile powder that will be terminally sterilized - Compounded bladder irrigations - TPN for terminal sterilization by final filtration

29. Environmental Quality Control • Work bench area: where compounding is completed • Buffer area = clean room: area immediately surrounding the work bench. Should not contain any drains or sinks. • Ante area: Space beyond the buffer area where hand sanitizing and gowning occurs. - includes hands free faucets and air dryers or low-shedding towels. - Supplies are unpacked and disinfected for storage in the ante room.

30. Environmental Quality Control • General Requirements: - Must limit tasks performed in the buffer area to those directly related to compounding. - 2 stainless steel carts with cleanable castors; 1. one for buffer area 2. collecting medications solutions and supplies that are cleaned and sanitized before being transferred to the buffer cart for compounding.

31. Environmental Quality and Control Compounding personnel must be properly garbed in clean room FYI: A motionless person sheds 100,000 particles every 60 seconds…Skin flakes, hair, salt, oils, moisture droplets, even deodorant. For all risk levels: Hair covers, shoe covers, knee-length coats or coveralls with Snug writs and front closures face masks, and gloves

32. Training and Performance • Documentation for Tech training • Prior to commencing any compounding, perform a thorough didactic instruction in the theory and practice of sterile preparations, with evaluation of technique - annually for low and medium risk levels - semiannually for high risk levels • Compounder evaluations should include a formal written exam and practical evaluation of aseptic technique using growth media

33. Handwashing • Touching sterile products while compounding is the most common source of contamination of pharmacy prepared sterile products. • Scrub your hands, nails, wrists, and forearms thoroughly for at least 30 seconds with a brush, warm water, and appropriate bactericidal soap before performing aseptic manipulations. Wash your hands frequently and every time you re-enter the sterile compounding area. • Workers who have open sores on their hands or have an upper respiratory tract infection should inform their supervisor and/or consult the institutions quality assurance procedures. Wear sterile gloves and mask is needed.

34. Equipment and Supplies • Another important factor in aseptic preparation of sterile products is the correct use of appropriate sterile equipment and supplies, including syringes and needles. • Syringes: - made of either glass or plastic - most drugs are more stable in glass, so glass syringes are most often used when medication is to be stored in the syringe for an extended period of time. - Composed of a barrel and plunger. To maintain sterility of the product, do not touch the syringe tip or plunger. Many syringes have a locking mechanism at the tip: Leur-lock, which secures the needle within a threaded ring.

35. Syringes continued… • Available in numerous sizes ranging from 0.5 to 60 mL. Usually the larger the syringe capacity, the larger the interval between calibration lines. • Ideally, the volume of solution should only take up ½ to 2/3 of the syringe capacity. This avoids inadvertent touch contamination caused when the syringe plunger is pulled all the way back. • When measuring with a syringe, lineup the final edge (closest to the tip of the syringe) of the plunger piston, which comes in contact with the syringe barrel, to the calibration mark on the barrel which corresponds to the volume desired.

36. Syringes continued… • The syringe package should be opened within the laminar flow hood in order to maintain sterility. • The wrapper should be peeled apart and not ripped or torn. • To minimize particulate contamination, do not lay discarded packaging on the LAH work surface. • The syringe tip protector should be left in place until it is time to attach the needle.

37. Needles • Sizes are described by two numbers: - Gauge: corresponds to the diameter of its bore, which is the diameter of the inside of the shaft. The larger the gauge the smaller the needle bore. Ex: the smallest needles have a gauge of 27, the largest needles have a gauge of 13. - Length: the needle shaft is measured in inches and usually ranges from 3/8 to 3 ½ inches.

38. Needles continued… • Components of a simple needle: - Hub: attached the needle to the syringe and is often color-coded to correspond to a specific gauge. - Shaft: the tip of the needle shaft is slanted to form a point. The slant is called the bevel, the point is called the bevel tip. The opposite end of the slant is termed the bevel heel. • No part of the needle itself should be touched. Needles should be manipulated by their over-wrap and protective covers only. The protective cover should be left in place until the needle and/or syringe are ready to be used.

39. Needles continued… • A needle shaft is usually metal and is lubricated with a sterile silicone coating. - For this reason, needles should never be swabbed with alcohol. • Some needles have built in filters and are meant to be used with products requiring frequent such as drugs removed from a glass ampule.

40. Drug Additive Containers • Ampules - Composed entirely of glass and once broken (opened) become open-systemcontainers - Since air or fluid may now pass freely in and out of the container, it is not necessary to replace the volume or fluid to be withdrawn with air. - Before an ampule is opened, any solution visible in the top portion (head) should be moved to the bottom (body) by swirling the ampule in an upright position, tapping the ampule with your finger or inverting the ampule and then quickly swinging it into an upright position.

41. Ampule continued… • To break an ampule properly, the head must be broken from the body of the ampule. To make the break properly, the ampule neck is cleansed with an alcohol swab and the swab should be left in place. • To withdraw medication from an ampule, the ampule should be tilted and the bevel of the needle placed in the corner space (or shoulder) near the opening. • To withdraw the solution, either use a flter needle and change to a regular needle BEFORE expelling the contents. Either way, the filter needle must not be used for both withdrawing from the ampule and expelling from the syringe, because doing so would nullify the filtering effort.

42. Ampules continued… • Usually the medication is withdrawn from the ampule with a regular needle and then the needle is changed to a filter needle before pushing drug out of the syringe.

43. Vials • Is a glass or plastic container with a rubber stopper secured to its top, usually by an aluminum cover. • They are used to hold powders and liquids. • The rubber stopper is usually protected by a flip-top cap or aluminum cover. • Most protective covers do not guarantee sterility of the rubber stopper; therefore, before the stopper is penetrated, it must be swabbed with 70% isopropyl alcohol and allowed to dry.

44. Vials continued… • Swabbing helps achieve sterility in two ways: - the alcohol acts as a disinfecting agent - the physical act of swabbing in one direction removes particles. • When piercing vials with needles, avoid coring fragments out of the rubber stopper with the needle. - a core is carved out of the rubber stopper when the bevel tip and the bevel heel do not penetrate the stopper at the same point. • Vials are closed-system containers since air or fluid cannot pass freely in or out of them.

45. Vials continued… • In most cases, air pressure inside the vial is similar to that of room air. • In order to prevent the formation of a vacuum inside the vial (less pressure inside the vial than room air) the used should normalize pressure by first injecting into the vial a volume of air equal to the volume of fluid that is going to be withdrawn. • If the drug is in powdered form, it has to be reconstituted. Inject the desired volume of sterile diluting solution (the diluent), such as sterile water for injection, into the vial containing the powdered drug.

46. Vials continued… • An equal volume of air must be removed in order to prevent a positive pressure from developing inside the vial. • Vials with drugs in solution are classified as multiple-dose (also called multiple use) or single-dose. • Multiple-dose vials contain a small amount of a preservative agent, added to retard the growth of bacteria or other organisms that inadvertently contaminate a product. • Single-dose vials have no preservative and are intended to be used one time only. Once a vial is entered with a needle, it should be discarded.

47. Pre-filled Syringes • Drugs commonly given IM or IV are packaged this way to make them convenient for the health care provider. • It is also done if the drug is commonly used in emergency situations because a pre-filled syringe saves time.

48. Preparation of Intravenous Admixtures • Before compounding – assemble all materials and visually inspect vials, ampules, and IV solution containers for signs of cloudiness, particulate matter, cracks and punctures, expiration dates, and anything else that may indicate that the product is defective.

49. Preparation continued… • Next, disinfect all injection surfaces and allow them to dry. - Flexible plastic bag – made of polyvinyl chloride (PVC) are frequently used. - Easier to store, less breakable than glass bottles, and eliminates the need to vent the container when removing fluid. - The protective overwrap should not be removed from a PVC bag until it is ready to be used. - To minimize air turbulence in the critical area, position the injection port of a PVC bag, which is covered by an outside latex tip diaphragm, toward the HEPA filter when preparing an IV admixture.

50. Disposal of Supplies • Syringes and uncapped needles should be discarded according to institutional policy. • Never recap a needle. Lay the syringe horizontally and slide the cap onto the needle. Or place the syringe vertically and drop the cap onto the needle. • In some institutions supplies are discarded in puncture-resistant, sealable containers often called sharps containers.