Nonsterile Pharmaceutical Compounding Chapter 8 Created by Jennifer

Non-sterile Pharmaceutical Compounding Chapter 8 Created by Jennifer Majeske, Mineral Area College

Learning objectives Define the term compounding, describe common situations in which compounding is required, and identify rationale and examples of non-sterile compounding. Discuss the impact of the Food and Drug Administration Modernization Act (FDAMA) of 1997 on the practice of a compounding pharmacy. Understand the distinction between a manufactured product and a compounded non-sterile preparation. Created by Jennifer Majeske, Mineral Area College

Learning objectives Define the regulatory role of the state board of pharmacy. Identify quality standards for nonsterile compounding contained in USP Chapter <795>, including product selection and beyond-use or expiration dating. Review and follow the components of good compounding practices in the pharmacy. Discuss reasons and process for accreditation of specialty compounded pharmacies. Created by Jennifer Majeske, Mineral Area College

Learning objectives Understand the minimum training and attire requirements for pharmacy technicians in a compounding pharmacy. Distinguish the components and purpose of a master control record from a compounding log. Define the term percentage of error and understand how the concept relates to accuracy in the compounding pharmacy. Created by Jennifer Majeske, Mineral Area College

Learning objectives Identify and describe the function of the equipment used for the weighing, measuring, and compounding of pharmaceuticals. Explain the proper techniques for weighing pharmaceutical ingredients, measuring liquid volumes, and compounding nonsterile preparations. Define the various terms used for comminution and blending of pharmaceutical ingredients. Created by Jennifer Majeske, Mineral Area College

Learning Objectives Examine the techniques by which solutions, suspensions, ointments, creams, powders, suppositories, and capsules are prepared. Understand calculate common mathematical problems that occur in a compounding pharmacy. Identify the steps that are necessary in the compounding process. Compare reimbursement procedures of a compounding pharmacy and a retail pharmacy. Identify references with a specialty focus on compounding. Created by Jennifer Majeske, Mineral Area College

The need for compounding Until the mid-nineteenth century, pharmacists routinely prepared (compounded) a majority of all prescriptions. With large-scale manufacturing the need for compounding has lessened, some trends however indicate the practice is increasing. Approximately 30 -40 million prescriptions are compounded in the U. S. each year. Extemporaneous compounding – compounding of nonsterile preparations or products that are not commercially available. Created by Jennifer Majeske, Mineral Area College

Sterile and Non-sterile Compounding – the process in which a pharmacist uses bulk ingredients to prepare a prescribed medication that treats a specific patient’s medical condition. Sterile compounding – the process of using aseptic technique to prepare sterile solutions, or solutions that are free of microorganisms, for parenteral products or ophthalmic preparations. Most sterile compounding is performed in the “clean room environment. ” Created by Jennifer Majeske, Mineral Area College

Sterile and Non-sterile Compounding Sterile compounding must be performed under strict controlled environmental conditions to minimize the risk of contamination of the compounded sterile preparations (CSPs). CSPs are administered parenterally; prepared under strict federal and state regulations. Most CSPs do not contain a preservative; these products have a brief beyond-use date of 24 – 72 hours due to sterility rather than stability concerns. Created by Jennifer Majeske, Mineral Area College

Non-Sterile Compounding Non-sterile compounding – used in the preparation of commercially unavailable drug formulations from bulk ingredients in the community pharmacy. Individualized prescriptions for patients. Unique medication requirements for animals; catering to an animal’s species and size. What are some of the possible scenarios for non-sterile compounding? What is the role of the technician in nonsterile compounding? Created by Jennifer Majeske, Mineral Area College

Laws, Regulations, and Standards For sterile and non-sterile compounding, federal and state laws and regulations along with United States Pharmacopeia (USP) standards and guidelines must be followed. Professional organizations: ◦ International Academy of Compounding Pharmacists (IACP), American Pharmacists Association (APh. A), American Society of Health-System Pharmacists (ASHP), National Community Pharmacists Association (NCPA) Compounding pharmacies are allowed to advertise their services, but not the compounding of specific preparations. Created by Jennifer Majeske, Mineral Area College

Food and Drug Administration Modernization Act of 1997 Before 1997, there were no specific federal or state laws governing the practices of pharmacy compounding. Pharmacists are allowed to, under the Food and Drug Administration Modernization Act of 1997, compound non-sterile and/or sterile medications for a patient if these medications meet USP standards. Public health concerns are minor when mass production is not involved. Compounded products are typically used for a small group of patients with specific medical needs. Created by Jennifer Majeske, Mineral Area College

Compounding Regulations Compounding pharmacies must be licensed by both state and federal governments. Anticipatory compounding – pharmacies are allowed to prepare an excess product, as long as quantities are reasonable. Pharmacies that compound and sell directly to other pharmacies or healthcare providers must apply for a manufacturing license. The need for additional regulations was obvious in 2012 with an outbreak of fungal meningitis from epidural injections of a contaminated corticosteroid. ◦ http: //www. cdc. gov/hai/outbreaks/meningitis. html Created by Jennifer Majeske, Mineral Area College

USP Chapter <797> USP has developed standards to enhance patient safety and protect pharmacists from litigation. USP Chapter <795> outlines protocol for nonsterile compounding; USP Chapter <797> outlines regulations for sterile compounding. Manufactured products – produced by pharmaceutical manufacturers (Eli Lilly and Merck). Compounded preparations – produced by pharmacies. Good compounding practices (GCPs) – Table 8. 1; all compounded products should be prepared using GCPs. Created by Jennifer Majeske, Mineral Area College

Non-sterile Compounding Environment Quality controls consists of the use of highgrade pharmaceutical ingredients along with training of personnel, the preparations stability and consistency, safeguarding against calculation errors and documentation. General Facility Requirements: ◦ ◦ ◦ Adequate storage and space Appropriately maintained equipment High cleanliness Free of dust Must have an eyewash station Physically separate from the dispensing pharmacy Created by Jennifer Majeske, Mineral Area College

Product Inventory Quality of ingredients; only USP or National Formulary (NF) pharmaceutical-grade. Sources for Bulk Ingredients: The source for ingredients depends on cost, quality, and purity of product. ◦ Pharmaceutical Compounding Centers of America (PCCA) is a primary source of products Pharmacists should have more than one source of quality ingredients. Table 8. 2 Bulk Product Contacts Created by Jennifer Majeske, Mineral Area College

Product Inventory Storage of Bulk Ingredients: Ingredients are commonly ordered two to three times a week depending on volume and inventory. Material Safety Data Sheet (MSDS) or Safety Data Sheet (SDS) – contains important information on hazards and flammability of chemicals and procedures for treatment of accidental ingestion or exposure. Bulk ingredients are typically stored in tight, light resistant containers at room temp. The technician should check expiration dates, the source of the ingredients, and the NDC number. Created by Jennifer Majeske, Mineral Area College

Product Inventory Controlled Substances Inventory: Procedures and recording keeping for Schedule II compounds are detailed and extensive. Controlled substance inventory must be in locked storage accessible only to the pharmacist. Beyond-Use Dating – the expiration date of compounded preparations based on stability and temperature storage conditions. Stability – the extent to which a product retains the same properties and characteristics that is possessed at the time of preparation. Created by Jennifer Majeske, Mineral Area College

Beyond-Use Dating Beyond-use dating is initiated at the time of compounding. Compounds should be prepared as close to the time of patient dispensing as possible. USP Chapter <795> provides estimates for beyond-use dating. ◦ Refrigerated aqueous solution or suspension has a beyond-use dating of 14 -30 days. ◦ Solids, like tablets and capsules and non-aqueous solutions have a beyond-use date of 6 months or less. ◦ All other formulations have a 30 -day beyond-use date or duration of therapy, whichever date is earlier. Created by Jennifer Majeske, Mineral Area College

Beyond-Use Dating A beyond-use date for a prescription of two or more active or inactive ingredients with varying expiration dates is trickier. The beyond-use date is determined by taking 25% of the remaining expiration date or 6 months, whichever is earlier. If dates differ, the earliest date is used. Examples 1 & 2 provide practice calculating the beyond-use of non-sterile preparations. Conservative beyond-use dating guidelines in USP Chapter <795> are most often used. Created by Jennifer Majeske, Mineral Area College

Accreditation Compounding pharmacies are seeking national accreditation to protect patents and business from legal challenges. Pharmacy Compounding Accreditation Board (PCAB) – accreditation organization; provides quality and safety standards for voluntary accreditation. Continuous quality improvement (CQI) – the process of written procedures in the PCAB standards designed to identify problems and recommend solutions. Created by Jennifer Majeske, Mineral Area College

Regulations for Pharmacy Personnel Technicians in order to work in compounding pharmacies must obtain special certification and training. Certification of Pharmacy Technicians: Non-sterile Compounding Attire: ◦ Special certification (PCCA) ◦ Training ◦ ◦ ◦ ◦ Clean protective clothing Hairnet Long lab coat Disposable gloves Eye goggles Masks Double gowning Hand washing – liquid antimicrobial soap, minimum of 15 seconds Created by Jennifer Majeske, Mineral Area College

Documentation of Non-sterile Compounding Documentation of all active and inactive ingredients, procedures for sequencing and mixing. Master Control Record – the recipe. The master control record lists: ◦ Drug’s name, strength, and dosage form ◦ Ingredients and quantities ◦ Sequencing and mixing instructions Includes the recommended beyond-use date, storage and labeling requirements. Created by Jennifer Majeske, Mineral Area College

Compounding Log Compounding log – generated for each prescription. The compounding log is used to document calculations and any special equipment. Prescription record – computer-generated copy of the log, stored and retrievable for future refills. What is listed on the compounding log? Figure 8. 2 pg. 322 in your book is an example of a compounding log. Created by Jennifer Majeske, Mineral Area College

Calculations in the Compounding Pharmacy Technicians must have a thorough knowledge of mathematical conversions and a good aptitude for performing calculations in a compounding pharmacy. A double check by both the pharmacist and technician is strongly recommended to minimize medication errors. All measurements and calculations must be documented and reviewed by the pharmacist during the final check of a compounded preparation. Created by Jennifer Majeske, Mineral Area College

Equipment for Weighing, Measuring, and Compounding A variety of equipment is utilized in a compounding pharmacy. Technicians need to be familiar with the equipment, its uses, and maintenance. All materials needed for proper packaging and labeling must be ensured by the pharmacy technician. Caution needs to be used for equipment in both sterile and non-sterile compounding pharmacies. Created by Jennifer Majeske, Mineral Area College

Measuring Devices for Solids Accurately weighing ingredients is one of the most essential parts of compounding. Technicians must be comfortable using various balances when weighing products. Familiarity with the device’s calibration is important when operating any type of balance. Two-Pan Balances: ◦ Class III prescription balance, Class A prescription balance ◦ Counterbalance Created by Jennifer Majeske, Mineral Area College

Pharmaceutical Weights for Two. Pan Balances Weights are used for both measurement and calibration. Pharmaceutical weights – a standardized set, used to offset the ingredient weight. Weights are generally made of polished brass, and can be coated with a non-corrosive material. Sets contain metric and apothecary weights. Typical sets are in grams, fractional grams (mg) and avoirdupois weights. Weights are placed on the right pan; material to be weight on the left pan. Created by Jennifer Majeske, Mineral Area College

Handling and Storage of Weights Forceps – an instrument used for grasping and holding small objects; weights should be transferred using forceps not fingers. A cloth should be used when handling larger weights. Weighing paper – is placed on the pans to protect the balances from damage and to avoid contact between pharmaceutical ingredients and the metal trays. Weighing boat – used to weigh larger quantities of chemicals. Created by Jennifer Majeske, Mineral Area College

Digital Electronic Analytical Balance Digital electronic analytical balance – uses a single pan and is easier to learn to use and more accurate than a Class III balance or counterbalance. Operating an Electronic Balance: ◦ Placed on a secure, level, and non-vibrating service at waist height; perfectly level. ◦ Calibration must be documented. ◦ Avoid spilling. ◦ Table 8. 3 pg. 326 Steps for Using an Electronic Balance Created by Jennifer Majeske, Mineral Area College

Balances and Percentage of Error Created by Jennifer Majeske, Mineral Area College

Measuring Devices for Liquids Volumetric measurement – measuring of liquid volumes. Graduated cylinders – a glass or polypropylene flask used for measuring liquids. Conical graduates have wide tops and narrow bases and taper from top to bottom. Cylindrical graduates are more accurate and have the shape of a uniform column. Table 8. 4 pg. 328 Measuring Liquid Volume Created by Jennifer Majeske, Mineral Area College

Using a Graduated Cylinder Be sure the cylinder is on a flat surface. Read the volume measurement at the bottom of the meniscus. Meniscus – the half-moon-shaped or concave appearance of the upper surface of a liquid. Measure at eye level, not by looking down on the container. Viscous liquids may take longer to get an accurate measurement of the meniscus. Created by Jennifer Majeske, Mineral Area College

Measuring Devices for Liquids Pipette – a long, thin, calibrated hollow glass tube that is used for accurate measurement and transfer of small volumes of liquid. Oral Syringes and Droppers: ◦ Oral syringes (hypodermic syringes without a needle) can be used to measure large or small quantities of liquids. ◦ Oral syringes are more accurate when measuring thick, viscous liquids. ◦ Droppers can be used to transfer small volumes of liquid; droppers must be calibrated because the drop size will vary between liquids. Created by Jennifer Majeske, Mineral Area College

Supplies for Making and Molding Ingredients Mortar and pestle – widely used in the compounding of liquids and solids. ◦ Glass, porcelain, and Wedgwood. ◦ Course-grained porcelain or Wedgwood is used for triturating (or pulverizing) ◦ Glass, with its smooth surface, is preferred for mixing liquids, creams, ointments, and gels. Electric mortar and pestle is often used in a highvolume compounding pharmacy. Beakers and Flasks – non-volumetric glassware. ◦ Can only approximate larger volumes of liquids; not used when an exact measurement of liquid is required. Ointment Mill – three-roller mills mixes and reduces particle size. ◦ Results in a smoother, more pharmaceutically elegant end product. Created by Jennifer Majeske, Mineral Area College

Supplies for Mixing and Molding Ingredients Ointment slab – compounding slab; made of ground glass. ◦ Compounding may also be performed on special disposable nonabsorbent parchment paper. Spatula – an instrument used for preparing ointments and creams, loosening material from the surface of a mortar and pestle, transferring solid pharmaceutical ingredients. ◦ Stainless steel, plastic, or hard rubber ◦ Hard rubber spatulas are used with corrosive substances Molds and Presses – to make rectal and vaginal suppositories or oral rapid-dissolving tablets and troches. Created by Jennifer Majeske, Mineral Area College

Containers for Packaging Compounded products are stored in a variety of packages. Most products will be in amber-colored vials or bottles. Special packaging may be required. Topi-CLICK Delivery System: ◦ ◦ Used for delivery of topical creams Holds up to 35 m. L Can provide 1 -3 months of medication Topi-CLICK delivery system promotes patient compliance and has accuracy unmatched by the traditional tube delivery method Created by Jennifer Majeske, Mineral Area College

Techniques for Mixing Compounded Drugs Before preparing a compounded product the technician should have the master control record, ingredients, equipment, etc. Adequate and uninterrupted time should be provided to the person compounding. Utilizing the best technique for the mixing of active and inactive ingredients is something the technician must learn. The best technique should be included in the master control record or suggested by the experienced compounder. Created by Jennifer Majeske, Mineral Area College

Comminution and Blending Comminution – the act of reducing a substance to fine particles. Blending – the act of combining two substances. Trituration – the process of rubbing, grinding, or pulverizing a substance to create fine particles. ◦ Diluent powder – an inactive ingredient that is added to the active ingredient when compounding a capsule. Levigation – a technique used when reducing the particle size of a solid during the preparation of an ointment; a levigating agent – castor oil, glycerin, or mineral oil – is slowly added to the ingredients to wet (not dissolve) the insoluble substance. Created by Jennifer Majeske, Mineral Area College

Comminution and Blending Pulverization – the process of reducing the size of particles in a solid with the aid of an additional ingredient in which the substance is soluble. Spatulation – the process of combining and mixing substances by means of a spatula, generally on an ointment slab or tile. Sifting – a process not unlike the sifting of flour in baking, using a wire mesh sieve. Tumbling – used to mix powders in a resealable plastic bag or a glass bottle and “tumble” or rotate the container to mix the ingredients well. Geometric dilution method – the most potent ingredient is added first, followed by the next most potent ingredient adding each time an amount equal to the amount in the mortar. ◦ Example 4 Created by Jennifer Majeske, Mineral Area College

Compounding of Specific Formulations Powders – a finely divided combination, or admixture, of drugs and/or chemicals ranging in size from extremely fine to very coarse. ◦ Goody’s Headache Powder, individually wrapped ◦ Metamucil, bulk powder Types of Powders: most active and inactive ingredients come in bulk powder form. ◦ Size range: very coarse (No. 8 powder), coarse (No. 20 powder), moderately coarse (No. 40 powder), fine (No. 60 powder), or very fine (No. 80 powder). Mixing of Powders: powders are combined by trituration, spatulation, sifting and tumbling, or automated equipment. ◦ Example 5 Created by Jennifer Majeske, Mineral Area College

Tablets and Troches Rapid-dissolving tablets or troches are typically compounded in a special contained hood to minimize airborne contamination. Rapid-dissolving tablets (RDTs) – unique tablet formulation that disintegrate rapidly and dissolve on the tongue within 30 seconds. Troches – small, circular lozenges that contain active medication. Created by Jennifer Majeske, Mineral Area College

Capsules A solid dosage form consisting of a gelatin shell that encloses the medicinal preparation, which may be a powder, granule, or liquid. Hard-shell capsules standard sizes are 5, 4, 3, 2, 1, 0, 000 (smallest to largest). Hard-shell capsules are meant to be swallowed whole; some can be opened and sprinkled on food or in drink. Filling Capsules: ◦ Punch Method: used when hand-filling a capsule with powder. ◦ Capsule Machine: metal plates used to replace the one-at-a -time punch-and-fill method; a capsule machine can make 100 capsules within a short time period. ◦ Example 6 Created by Jennifer Majeske, Mineral Area College

Solutions A liquid dosage form in which the active ingredients are dissolved in a liquid vehicle. Solvent – the vehicle that makes up the greater part of a solution. Solute – the ingredient dissolved in the solution. Solutions can be aqueous, alcoholic or hydroalcoholic. Created by Jennifer Majeske, Mineral Area College

Suspensions In a suspension, the active ingredient is not dissolved in the liquid vehicle but is rather dispersed throughout it. What problem exists with suspensions? The auxiliary label “Shake Well” should always be affixed to a suspension. Pediatric suspensions can be prepared that are commercially unavailable. Example 7 Created by Jennifer Majeske, Mineral Area College

Ointments, Creams, and Lotions Ointments: ◦ water-in-oil (w/o) emulsion that is occlusive, greasy, and not water-washable. Creams: ◦ oil-in-water (o/w) emulsion that is nonocclusive, nongreasy, and water-washable. Lotions: ◦ liquid suspension or oil-in-water emulsion used topically. ◦ Example 8 Created by Jennifer Majeske, Mineral Area College

Ointments, Creams, and Lotions Compounding Ointments, Creams, and Lotions: ◦ dermatologic therapies may call for combining existing ointments or creams; dry powders may have to be added to an ointment or cream base. Compounding Hormone Formulations: ◦ Hormone replacement therapy (HRT) – combines estrogen, progestin (female) androgen (male) to relieve specific postmenopausal symptoms. ◦ Estrogen replacement therapy (ERT) – female hormones sometimes used in postmenopausal women and premenopausal women who have had complete hysterectomies. Created by Jennifer Majeske, Mineral Area College

Suppositories Solid dosage forms that are inserted into the body’s orifices, generally the rectum or vagina. These dosage forms melt when exposed to body heat and fluids. Suppositories are produced by molding and compression. Patients should be advised to refrigerate the medication, why? Created by Jennifer Majeske, Mineral Area College

The Compounding Process Each step of the compounding process is checked by the pharmacist and technician. Table 8. 6 Steps in the Compounding Process on pg. 344 outlines the steps required by USP Chapter <795>. Selecting Medication Containers: ◦ Tablets and capsules should be stored in ambercolored vials to protect the product from light. ◦ Ointments and creams may be placed in white ointment jars. ◦ Suppositories and pellets may be dispensed in cardboard boxes. Created by Jennifer Majeske, Mineral Area College

Labeling and Cleanup The compounded preparation must be labeled with all information for the consumer as required by state and federal governments. The label should include: ◦ Beyond-use date ◦ Lot number ◦ Date of compounding Equipment should be cleaned and properly stored after use. Hazardous chemicals should be disposed of in a proper manner. Created by Jennifer Majeske, Mineral Area College

Final Check by the Pharmacist The pharmacist is legally responsible for the check of the final product. What sort of things does the pharmacist verify as part of the final check? Pharmaceutical elegance – or how the product looks. Easy retrievability is important if there is a drug recall of any ingredients used in the compounded prescription. Created by Jennifer Majeske, Mineral Area College

Patient Counseling by the Pharmacist The patient needs to understand that his or her prescription has been individually prepared and compounded. Patients should be made aware of the ingredients in the compound and how to take the medication. Patients should be counseled on proper storage conditions as well as labeling requirements. Created by Jennifer Majeske, Mineral Area College

Reimbursement Insurances do not generally cover the cost of compounded medications. The cost of a compounded medication is based on the time and experience of the compounder, and minimally on the active and inactive ingredients. Some insurance companies will reimburse later on compounded prescriptions. Success for reimbursement appears to be greater if the patient submits the claim, rather than the pharmacy. Created by Jennifer Majeske, Mineral Area College

Reference Sources for the Compounding Pharmacy Remington: The Science and Practice of Pharmacy Professional Compounding Centers of America (PCCA) http: //www. pccarx. com/ United States Pharmacopeia (USP) http: //www. usp. org Secundum Artem: Current & Practical Compounding Information for the Pharmacist International Academy of Compounding Pharmacists (IACP) http: //www. iacprx. org/ Created by Jennifer Majeske, Mineral Area College

This workforce solution was funded by a grant awarded by the U. S. Department of Labor’s Employment and Training Administration. The solution was created by the grantee and does not necessarily reflect the official position of the U. S. Department of Labor. The Department of Labor makes not guarantees, warranties, or assurances of any kind, express or implied, with respect to such information, including any information on linked sites and including, but not limited to, accuracy of the information or tis completeness, timeliness, usefulness, adequacy, continued availability, or ownership. This work by Mineral Area College is licensed under the Creative Commons Attribution 4. 0 International License. Created by Jennifer Majeske, Mineral Area College