Sterile Products PDF

Specialty Sterile Products (*** Will be on the final exam) Specialty Parenteral Dialysates Irrigation Ophthalmics Radiopharmaceuticals Allergen Extracts...

Specialty Sterile Products (*** Will be on the final exam) Specialty Parenteral Dialysates Irrigation Ophthalmics Radiopharmaceuticals Allergen Extracts Dialysis Solutions DIALYSIS Definition Dialysis may be defined as the artificial process of eliminating waste from the blood. Our kidneys do this naturally but many patients with poor or no kidney function will require dialysis Dialysis allows all the waste and extra fluid to be “filtered” out of the blood much like a dirty swimming pool May need dialysis due to injury, poisoning and chronic renal failure or disease Dialysis - hemodialysis vs. peritoneal dialysis (exam review) Types of Dialysis*** HEMODIALYSIS Patients connected to an “artificial kidney machine” The patient’s blood comes OUT through a surgically inserted catheter inserted into a large artery or vein The machine will filter out waste from the blood using a semipermeable membrane and hypertonic dialysis solution Wastes include: urea, uric acid and creatinine The filtered blood is then returned INTO the patient through another catheter PERITONEAL Peritoneal dialysis solutions are instilled into the peritoneal cavity The abdomen includes the intestines, stomach, bladder, pancreas and spleen is surrounded by the peritoneum (semi-permeable membrane) Not as efficient as hemodialysis because it requires longer treatment time, but the total amount of waste and fluid removal is essentially the same Solutions are referred to as DIALYSATES PERITONEAL TERMS related to Peritoneal Dialysis EXCHANGE (or CYCLE) Dialysate is instilled into the peritoneum and remains so that it can absorb waste products. Solution is drained out through a tube. This cycle is repeated several times a day DWELL The amount of time the dialysate will remain in the peritoneum  Dialysates Commercially available in different sizes and concentrations Hypertonicity causes diffusion of waste from blood Sterile manipulations of required additives in an ISO class 5 environment antibiotics to treat peritonitis heparin to reduce fibrin formation potassium for keeping electrolytes in balance Composition of Dialysates Resembles extracellular fluid Dextrose (glucose) varies 1.25% - 4.25% Electrolytes: sodium, chloride, calcium, magnesium, lactate/bicarbonate/acetate (buffers) Peritoneal Dialysis - Physician’s Order FREQUENCY FREQUENCY OF DWELL FLOW RATE VOLUME MANUALLY ADDED INGREDIENTS Intermittent - 3-5 days a week EXCHANGES (# How long does of of antibiotics, (IPD) times daily) the dialysate stay solution into dialysate bag heparin, KCl Continuous- (CAPD) inside body peritoneum Common ingredients in irrigation solutions (exam review) Irrigation Solutions*** Similar composition to IV solutions Must be prepared under same strict conditions as injectables Must be clearly labelled ‘not for injection’ May have different packaging such as screw tops to distinguish from injectables Topical Irrigation of wounds Urologic Irrigation of bladder Occasionally medication may be aseptically added to irrigation fluid Common ingredients in irrigation solutions Irrigation Solution Examples*** Acetic Acid Irrigation Solution- USP Topically to the bladder - 0.25% solution Used during urologic procedures Administered to rinse blood and surgical debris during procedures Improves the conditions of the tissue and allows an unobstructed view for the surgeon Neomycin and Polymyxin B Solution for Irrigation Sterile solution containing neomycin sulfate and Polymyxin B Sulfate Used as a topical antibacterial in a continuous irrigation of the bladder 1 mL of this solution is added to 1 L of NS and administered over a 24-hour period Sodium Chloride for Irrigation Similar composition to NaCl for injection Available in 0.9% or 0.45% strength Applied topically to clean wounds and body cavities Labelled for irrigation only Sterile Water for Irrigation USP Same as sterile water for injection but does not meet particle count levels required for injection Does not contain preservatives Used a vehicle for antimicrobial agents Labelled for irrigation only  RADIOPHARMACEUTICALS Definition: Indications for use: A radioactive pharmaceutical agent or drug used for Two major areas diagnosis or therapy Diagnostic Contain a radioisotope component and a drug molecule most established indication component Therapeutic growing and evolving Basic knowledge of elution on radiopharmaceuticals =Know your terms (exam review) RADIOPHARMACEUTICALS OVERVIEW Radioisotopes emit low levels of radiation gamma rays alpha particles beta particles Mainly used as non-invasive tracers of physiologic processes within the body May be administered in a vein, orally or in body cavities AVAILABLE DOSAGE FORMS: IV solutions Intrathecal solutions Suspensions Oral solution Capsules Aerosols for inhalation DIAGNOSTIC PURPOSES THERAPEUTIC PURPOSES Help to diagnose the presence and observe the progression of a Radiopharmaceutical therapy has significant advantages over disease and evaluate drug induced toxicity Chemotherapy/Radiation treatments Important characteristic is the product must “target” the required Minimizes side effects organ or area of the body Selective in nature to target specific organs or sites Examples Expose neighbouring cells to irradiation as well to improve Access function of cardiovascular system outcomes Cerebral blood perfusion Examples: Imaging tumours Thyroid cancers Neurological system imaging Conditions of the thyroid such as Grave’s and hyperthyroidism Bone pain Brain tumours PREPARATION DISPENSING Majority prepared for parenteral administration These agents never go to patients or nurse, they are provided to Very specialized process requiring extensive training a trained specialist in the hospital or clinic to be administered Prepared with same aseptic techniques as other sterile products Special labeling and packaging- lead sheath, caution label Prepare in an ISO Class 5 BSC (vertical airflow) with lead protection “Radioactive Material” screen to avoid exposure from radiation Syringes and containers shielded in lead Monitoring radioactivity contamination of environment and strict policies regarding handling of radioactive products Strength normally measured in millicurie (mCi) ***Example of the ELUTION PROCESS: 85% of medical imaging in nuclear medicine uses Tc-99m Technetium-99 Tc-99m (the “daughter”) is an isotope ELUTED (washed) from Molybdeumn-99 Mo-99 (the “parent”) Pouring 10 mL of isotonic saline solution through a column of Mo-99 ELUTES the soluble Tc-99m Ophthalmic: preparation requirement & bioavailability (exam review) Ophthalmics*** DOSAGE FROMS: Solutions Suspensions Gels Ointments Drug impregnated inserts Conditions Treated - Surface or Intraocular INFECTIONS ALLERGIC REACTIONS OR ELEVATED INTRAOCULAR PRESSURE GLAUCOMA EYE DRYNESS INFLAMMATION Ophthalmic*** Preparation Requirements*** Sterility Preservatives Isotonicity Buffering Viscosity Bioavailability of drug Packaging STERILITY PRESERVATIVES Most preferred method autoclaving Maintains sterility of preparation May also be sterilized via sterile membrane filter using incorporation of antimicrobial agent aseptic technique in LAFH Must not cause eye sensitivity Examples Benzalkonium chloride Benzethonium chloride Chlorobutanol Thimerosal ISOTONICITY BUFFERING Body fluids including blood and lacrimal fluid (tears) have pH adjustment of ophthalmics is required for: the same tonicity as NaCl 0.9% Providing comfort to the eye By comparison solutions with higher osmotic pressure than Improving product stability NaCl 0.9% are referred to as hypertonic and those lower Enhancing drug solubility than NaCl 0.9% are referred to as hypotonic Enhancing drug bioavailability Maximizing a preservative’s antimicrobial effect VISCOSITY / THICKENING AGENTS Viscosity reflects resistance to flow of liquid preparation Higher viscosity, longer contact time Temperature affects viscosity The warmer the temperature, the lower the viscosity (compare it to room temperature lip balm compared to when applied to lips) BIOAVAILABILITY*** the degree to which a drug or other substance becomes available to the target tissue after administration Important factor to ensure effectiveness of drug Gels and ointments have an increased bioavailability due to amount of contact time - higher viscosity Factors that can affect bioavailability include: Type of disease Drug metabolism Lacrimal drainage- tears contain enzymes that degrade drugs Physio-chemical characteristics of drug and it’s formulation ADDITIONAL FORMULATION CONSIDERATIONS Solutions must be clear Free from all particulate matter If product is to be in suspension, drug particles must be finely subdivided- micronized Suspended micronized particles must remain so at all times, or redistribute into solution following gentle shaking EXTEMPORANEOUS PREPARATIONS Not commercially available Different concentration of drug and/or dosage form required Required to be made with the same standards as an injectable preparation Prepared aseptically in a LAFH with ISO class 5 environment Research purposes Include: Antimicrobials Irrigating solutions Local anesthetics Anti-inflammatory Diagnostic ALLERGEN EXTRACTS Single or multi-dose intradermal/subcutaneous injections USP Chapter includes allergen extracts Trained pharmacy personnel Most often these products are compounded in a physician office or allergy clinic and adhere to Chapter requirements  Quality Assurance and Quality Control *** will be on exam Terms and Definitions*** Quality Assurance (QA): A system of steps and actions to ensure compliance to standards related to sterile compounded products Quality Management and Quality Improvement changing and improving processes and procedures to ensure a quality assurance program is current and well established Quality Control (QC): The analytical testing of the finished product and assessments of operations within the pharmacy to ensure standards are met Quality Assurance To monitor all processes including policies and procedures, facilities, equipment, and personnel involved in the preparation of sterile products Ensure compliance to established standards of practice Identify potential problem areas and take corrective action Ensure the quality of the product and the safety of patients and personnel are not jeopardized Ensure the compounded sterile product is clinically effective and adverse effects are identified and monitored Ensure the integrity of the compounded sterile product COMPONENTS OF A QUALITY ASSURANCE PROGRAM*** Standards/guidelines of practice for compounded sterile products (CSPs) Contributing partners:  Canadian Society of Hospital Pharmacists (CSHP)  NAPRA  OCP  USP Chapter COMPONENTS OF A QUALITY ASSURANCE/QUALITY CONTROL PROGRAM*** Policies and procedures Policies and procedures Personnel Written P&P regarding: Raw materials  Monitoring – equipment and facilities Storage and handling  Evaluating – personnel and final products Facilities and equipment  Correcting – contamination and errors Product preparation  Improving – systems and processes Labelling and documentation Process validation PERSONNEL RAW MATERIALS Identify and outline:  STERILE- sterile components properly prepared & disinfected Responsibilities  NON-STERILE- compendia standard grade, certificate of analysis Training & assessments and/or validation of identity, purity and potency prior to use STORAGE & HANDLING FACILITIES Components  Designated area properly constructed, controlled and maintained to  stored under conditions that ensure cleanliness, prevention of minimize microbial and particulate contamination contamination and degradation  ISO CLASS 5 environment -either a horizontal or vertical LAFH Finished products working bench in an ISO CLASS 7 cleanroom  must be stored under conditions that protect its physical and  A formal cleaning and disinfection program for floors, equipment, chemical integrity until use storage areas, ceilings, walls and working surfaces PRODUCT PREPARATION EXPIRATION DATING  Properly cleaned controlled areas Determined from references provided by:  Operator Manufacturer’s recommendations  Aseptic technique Pharmaceutical compendia  Sterilization USP  Checking and final product release Professional literature In-house stability/sterility testing  COMPONENTS OF A QUALITY ASSURANCE/QUALITY CONTROL PROGRAM LABELLING PROCESS VALIDATION  Patient specific or batching labels  Ensure that the drug meets all appropriate specifications for  Generic name(s)- ingredients/vehicles identity, strength, quality and purity  Concentrations  Equipment must be tested and certified at least annually or when  Volume relocated, repaired or maintained by qualified personnel to ensure  Route of administration efficiency and effectiveness  Storage requirements Aseptic technique  Expiration date/time  Validation of each type of aseptic procedure performed by  Special instructions trained personnel must be regularly performed and can include  Comply with provincial/federal legislation observation, gloved fingertip sampling, media fills, microbiological monitoring of surfaces PROCESS VALIDATION (cont’d) END PRODUCT TESTING Environmental monitoring Testing of completed CSPs for microbial content, quality and Air and surface sampling (viable and non- viable) potency Gauges and warning systems to alert personnel of pressure change Finished product being tested and/or undergoing verification in the compounding area must be appropriately stored in a quarantine area until released Documentation of process All products that fail to meet specifications must be rejected and All validation tests, cleaning and maintenance procedures must be disposed of or reprocessed, if appropriate, according to documented established procedures. DOCUMENTATION & RECORDS*** Why do we need to document? Records  Inspections – Health Canada or OCP  SOP updates  Legal situations  Compounding processes  Workload justification  Testing and certification of LAFH and controlled rooms  Quality improvement  Cleaning & maintenance  Teaching and training  Temperature logs of refrigerator, freezers and incubators **If it wasn’t documented, it wasn’t done!**  Environmental monitoring  Staff training  Aseptic technique assessment and certification FINISHED PRODUCT DOCUMENTATION  Ensures all procedures performed before, during and after compounding Good documentation will:  Validation that written policies and procedures were followed with respect  Identify who performed the task, when the task was performed to: and how the task was performed without the person being  Proper components used & checked prior to compounding present to justify/explain  Proper compounding methods used  Serve as control for quality and final preparation evaluation  Proper component quantities used and proper unit yield  Allow traceability in the event of an investigation to resolve  Correct and proper # of labels prepared and used adverse outcomes QUALITY CONTROL TESTS QUALITY CONTROL OF FINAL PRODUCTS*** PHYSICAL TESTS CHEMICAL TESTS  Container integrity pH- changes in pH may indicate instability  Leakage possible adverse effects  Particulate matter Purity  No visible particles in solution components meet compendia standards of  Weight of containers purity  Spot checks with calibrated pharmacy scale Stability  Colour maintain stability during specific storage  changes in colour may indicate interaction between components or conditions stability issues Potency  Volume of containers maintains potency up to the end of product’s  Odor shelf life  Gas formation indicating interaction between components Strength label strength is maintained up to the end of product’s shelf life STRENGTH VS. POTENCY*** Strength is often used interchangeably with potency, but they are not the same thing The amount of drug in a dosage form, for example, 500 mg/tablet is strength Potency refers to the relative strengths of medications that can produce the same effect. The drug with the lowest strength to produce the effect is said to be the most potent Effectiveness refers to the percent of patients who will have a desired response to a drug Strength can be confused with effectiveness when a patient asks if one drug is stronger than another QUALITY CONTROL TESTS*** Environment Environment Non-viable airborne particle level monitoring Microbial/viable airborne particle level monitoring Air sampling: Active Air sampling: Active  Measurement of total particle count and particle size found in the Inside the LAFH anteroom, cleanroom and LAFH Various locations in the cleanroom and anteroom  Use of volumetric air sampler to count particles >0.5µ in air sample to Uses volumetric air sampler assure ISO Class 5,7 or 8 Bio-burden levels of air samples must include:  Draws in a predetermined amount of air Baseline to test particle load Alert  Particle count should be conducted every 6 months or after a move or Action limit repair Action must be taken to determine source of particles  Best option is to be completed by an outside qualified agency Taken to lab to incubate to count CFUs and identify organism Environment Environment Microbial/viable airborne particle level monitoring Surface Sampling  Air Sampling: Passive Use of contact plates or swabs  TSA (Trypticase Soy Agar) settling plates set within the LAFH, Contact plates filled with general solid agar growth medium anteroom, cleanroom and neutralizing agents  Settling depends on particle size and influenced by air movement Plates used for regular or flat surfaces  Considered not suitable by USP Chapter /NAPRA Swabs are used for irregular surfaces  Not very accurate Plates incubated in lab CFU counted Microorganisms identified Environment Environment Pressure Measurements & Air Exchanges  Laminar air flow hoods  Air exchanges and pressure differentials  Regular performance testing - HEPA  Pressure and velocity air flow meters can be installed between the  Microbiological testing anteroom and clean room and the general environment outside the  Validation and calibration of automated compounding devices compounding area to monitor air flow and pressure dynamics (ACD) Temperature & Humidity Measurements  Validation and calibration of filling pumps  Temperature in anteroom and cleanroom  Validation and calibration of electronic balances  Less than 20C for compounder comfort  Recorded in general maintenance log  25C or less for drug storage  Cleanroom humidity range 30%-60 % relative humidity Finished Product Testing Personnel General Considerations  Compounding process validation  Requirements vary depending on level of risk, supplies and equipment  Aseptic technique validation used and storage time prior to use  Use of media fill – TSB (tryptic soy broth)  Low and Medium risk CSPs: are made from sterile supplies and  Fingertip testing sterile equipment, closed vessel technique, employing few  3 successful tests at initial training manipulations  1 successful test at recertification  High risk CSPs: use non-sterile components/containers would require  Training of new & existing personnel higher level of finished product testing  Certification and annual/biannual assessments Personnel Personnel Media-Fill Test Gloved fingertip sampling  Ideally a media-fill procedure should incorporate multiple manipulations After donning PPE and handwash (0 CFUs) using: After performing media fill test (no more than 3 CFUs combined  Syringes/needles on both hands)  Ampoules One plate for each hand (4 total)  Vials Incubated and microorganisms identified by lab  Injecting into media-fill bags  Compounding devices  Attaching transfer sets or tubing  Aseptic fill media should mimic the “worst-case” aseptic compounding procedures