Extemporaneous, Nonsterile Compounding

Compounding

• The process which uses bulk ingredients to prepare a prescribed medication that treats a specific patient’s medical needs

• Individualized order and not manufactured

• Involves art and skill

• Compounding

  • Sterile compounding

  • Nonsterile compounding

  • Extemporaneous compounding

Nonsterile Compounding

• Used to prepare medications in strengths, combinations, or dosage formulations that are not commercially available

• Pharmacy technicians and pharmacists generally need national certification and additional training to practice in a dedicated nonsterile compounding pharmacy

Why Would You Compound?

• Dosages for young children

• If a patient cannot swallow tablets/capsules; would make into a suspension, solution, or suppository

• Drug no longer available due to drug shortage or backorder

• Flavoring

• Topical gels whose oral equivalent has adverse effects on stomach

• Allergies to preservatives, colorings

• Hormone Replacement Therapy Cream/Gel to reduce the SE of tablet therapy

• Veterinary Medication

Nonsterile Compounding Laws, Regulations, and Standards

Food and Drug Administration Modernization Act of 1997

• Allows pharmacists to compound nonsterile medications for individual patients if these medications meet established USP standards

• Not required to meet Current Good Manufacturing Practices (CGMPs) which are regulatory standards for manufacturers

• Anticipatory Compounding: Allowed to prepare more than needed at the moment for refills or similar need; must be labeled with a lot number and beyond-use-date

• United States Pharmacopeia and National Formulary (USPNF)

  • USP Chapter <795> = nonsterile compounding

  • USP Chapter >797> = sterile compounding

  • USP Chapter <800> = hazardous drugs

  • Must follow Good Compounding Practices

  • (GCPs)

USP <795>

Any equipment or supplies used to compound MUST:

• Reduce ingredients to the smallest particle size

• Ensure the solution has no visible undissolved matter when dispensed

• Make sure preparations are similarly structured to ensure uniform final distribution

• Compounding pharmacies are overseen by FDA, USP, Accreditation Commission for Health Care, and state standards

• If hazardous materials are involved must follow OSHA rules (Occupational Safety and Health Administration) and NIOSH (National Institute for Occupational Safety and Health Administration)

USP Good Compounding Practices

USP GCPs

1. Facility: Designated area with adequate space away from routine dispensing and counseling functions, and high-traffic areas of the pharmacy (must have a separate area for sterile compounding). Must abide by USP <795> standards. This USP chapter gives detailed guidelines, policies, and procedures for the physical design and maintenance of the compounding area: vital to safe workflow. This area is cleaned daily and after each use. The lighting is tailored to the types of ingredients being compounded, as some are sensitive to light.

2. Personnel: Staff members with education, training, and proficiency in this specialized area; compounders must wear protective clothing; Accreditation by the Pharmacy Compounding Accreditation Board (PCAB) is recommended-holds pharmacies to strict guidelines to promote patient safety. The pharmacist is always responsible for the verification of all nonsterile products compounded by the technician.

3. Equipment: Appropriate design, size, and space of balances and measuring devices; equipment must be cleaned and calibrated daily. (record temperatures in refrigerator and freezer)

4. Ingredient Selection: Only high grade chemical, ingredients are used and stored appropriately. The raw chemical ingredients used must meet a minimum grade of purity (USP or NF is the minimum grade to be used)

5. Compounding Process: Each step reviewed by the pharmacist, who makes a final check of the completed process

6. Packaging and Storage: Properly store all ingredients, medications, 

      supplies, and formulations in the compounding area per the 

      Manufacturers’ labeling or USP-NF requirements. Hazardous 

      ingredients must follow USP<800> standards. NIOSH publishes a list of 

      hazardous ingredients yearly (ex) antineoplastics. All materials must be 

      stored so they will not chemically react with other medication or 

     ingredient in the formulation. For final packaging, consider strength, 

     visibility, moisture protection, ease of use and cost. Mark materials with 

     date of receipt and the date containers are opened. Rotate stock to use the oldest products first. Maintain products are at the correct temperature as indicated on the product label.

7. Controls: Quality control programs implemented by the pharmacist

8. Labeling of Excess Product: Labels showing quantity and lot number

9. Beyond-Use-Dating: Stability (and sterility in some cases) of preparation reflected in beyond-use-dating

10. Records and Reports: Documents including master formulation record, compounding record, and equipment maintenance, and logs and records of ingredients

11. Patient Counseling: Discussion with patient on safe administration and storage of the compounded preparation

The Role of the Technician in Nonsterile Compounding

• Retrieving the recipe

• Gathering necessary ingredients and equipment

• Calibrating the equipment

• Preparing products

• Ordering inventory ingredients

• Calculating beyond-use dates

• Printing and affixing

• Maintaining a clean work environment

• Special Training

  • Mini-certifications in nonsterile compounding

  • Professional Compounding Centers of America (PCCA)

  • The Accreditation Commission for Health Care (ACHC)

The Nonsterile Compounding Process and Documentation

• Must properly document and maintain records for all compounds

• Documentation can be kept with a written log book or electronically-will reduce exposure to legal liability and ensure consistency when formulations are compounded more than once

Four Sets of records Must be Kept in Compounding Areas

1. The Master Formulation Record

2. The Compounding Record

3. The Standard of Operating Procedures (SOP)

4. Ingredient Records

Master Formulation Record

• The compounding formula and procedure with detailed instructions and documentation of the source reference. Known as the “recipe.”

• Most pharmacy use MFRs by specialized organizations or business. ex) USP or PCCA (Professional Compounding Centers of America)

• Must be proven safe and effective and provide all the active and inactive ingredients, quanitites, and/or proportions, directions for proper sequencing, mixing and calculations.

• Provides: Calculations needed, compatibility and stability information on ingredients and final compound, equipment needed, directions to make, temperature, labeling information, BUD, packaging and storage requirements.

• The technician must follow each step in the compounding process as outlined in the Master Formulation Record and USP standards

Compounding Record

• Documents the ingredients used (listed with lot numbers, expiration and beyond-use-dates, manufacturer, and the amount used to compound, quantity made) and steps taken in the specific preparation process for each patient’s prescription; and individualized record for a specific batch. Lists the personnel involved in making the compound and the pharmacist verifying.

• Generated with each batch

• Filed as a permanent record

The Standard Operation Procedures (SOP)

• A detailed document with information about equipment, maintenance, equipment calibration, and handling and disposal of supplies

• Will also include the steps required by USP <795>

USP <795> 14 Steps to Compound a Nonsterile Preparation

**refer to handout

Personnel Praparation for Nonsterile Compounding

• CDC Handwashing and Hand Hygiene

  • Done before donning gloves or attire

  • Wash with soap and water

  • Use alcohol-based wipes for hygiene

Nonsterile Compounding Environment and Equipment

• Free of dust-collecting overhands

• Eyewash station

• Refrigeration and freezer equipment

• Potable water

• Purified water

• Non-shedding work surface

• Plumbing

• No food items stored or consumed in the staging area

Equipment

• Mortas and pestles (glass or porcelain)

• Ointment mills

• Ointment slabs

• Spatulas

• Digital or analytical two-pan balance

• Pharmaceutical weights

• Beakers

• Flasks

• Funnels

• Molds

• Weighing papers or parchment paper

• Graduated cylinders

• Pipettes

Nonsterile Compounding: Equipment and Supplies

Spatula - Stainless steel, plastic or rubber. Used to mix or transfer ingredients

Weighing paper/boats - Used to hold ingredients, protect balance surfaces, and transfer ingredients

Ointment slabs - Usually made of glass and used to mix powders, liquids, and creams

Ointment jars/tubes and dispensers - Final product for patient use are dispensed in these disposable plastic items

Heat sealers and crimping guns - Tubes and containers are sealed shut with heat sealers and crimping guns

Molds - Molds are used to shape troches, suppositories, and tablets. Made of aluminum or plastic.

Conical graduates - Wider at the top and narrower at the bottom

Cylindrical graduates - Uniform in size from top to bottom

• More accurate than conical

• Can be made of glass or plastic in many sizes

• Use smallest graduate possible to measure ingredients

• Beakers are cylindrical and used to mix or melt ingredients

• Ingredients are always measured at the level of the bottom of the meniscus

The mortal is the container, and the pestle is used to mic or grind. Mortars and pestles are made in different sizes and materials for various applications.

Porcelain is good for triturating ingreidnets, and glass is good to prevent staining

*triturating: reducing substances to fine particles

Compounding Ingredients

• Components

  • Active pharmaceutical ingredient

  • Added substances/inactive ingredients/excipients

  • Vehicle

Hazardous Compounding

• Compounding hazardous preparations requires additional personal protective equipment, such as special coat, double giving, a respiratory ask, a face shield, shoe and hair covers, and goggles

• A Safety Data Sheet (SDS) is required to be on file for all bulk ingredients stored in the pharmacy; a document from the manufacturer safe storage and handling that is required by OSHA for all bulk hazardous chemicals and drug substances; includes information on how to prevent an emergency or to address it if one occurs; must be kept on hand in the pharmacy

Weighing, Measuring, and the Percentage of Error

Potential Error and Percentage of Error

• Each different weighing or measuring device has a potential range of error known as the sensitivity range. It is the incremental unit that the device uses to measure, which is how much it can be off measurement.

  Actual amount measured - desired (prescribed) quantity = amount of error

• Percentage Error is the range of potential error in the weight or measurement, compared to the desired quantity

  Sensitivity range/Desired quantity x 100 = % of error in product

If you do not know the sensitivity range but you know the amount of error you can use this formula:

error amount/desired quantity x 100 = % of error in product

The official USP guidance allows for a deviation range of plus or minus 5%

Least Weighable Quantity per Scale

• Most balance are marked with their degree of accuracy and their least weighable quantity (LWQ)

• If you weigh a substance that is under the LWQ will result in an unacceptable margin of error

• A Class III balance has a LWQ of 120 mg

Bioavailability Range

• The percentage of how much of thee substance is absorbed in this product

The Processes of Weighing and Measuring

• Proper technique and use of correct measuring devices are crucial when weighing and measuring pharmaceutical ingredients

• Balances and Weight

  • Electronic digital balance

  • Two-pan balances

Nonsterile Compounding: Equipment and Supplies

Balances - Used to weigh pharmaceutical ingredients

Class A - Weigh smaller amounts

Electronic balances - Weigh larger amounts

*Brass weights are used to calibrate balances and should never be touched with ungloved hands

Volumetric Measurement

• Graduated Cylinders are used to measure liquids

• The volume of the liquid must be measured by the level of the center of the meniscus

• Pipettes

• Droppers

• Oral syringes

Techniques for Ingredient Preparation and Blending

• Mixing methods

  • Comminutions

    • Trituration

    • Levigation

    • Pulverization

  • Blending

    • Spatulation

    • Sifting

    • Tumbling

    • Geometric dilution

Techniques for Ingredient Preparation and Blending

• Geometric dilution is utilized when mixing two or more ingredients of different strengths or concentrations with a diluent, such as a solute, cream, or ointment base

• Start with the most potent ingredient first then add an equal amount of diluent and mix well. Repeat with other ingredients.

Compounding Specific Delivery Forms

• Powders

• Tablets

• Capsules

• Troches

• Solutions

• Suspensions

• Ointments/Creams/Lotions

• Suppositories

• The compounding of lozenges or troches often requires heating the solution and pouring it into molds to form their shapes as the liquid cools.

Hormone Compounds

• Hormone creams and ointments are the most common nonsterile compounded preparations, and they often require mixing the ingredients on a slab with a spatula or in an ointment mill

• Dosage is individualized per patient

• Topi-CLICK is a unique patented drug delivery system to more accurately and safely administer bioidentical hormones

Medication Containers and Beyond-Use Dating

• Containers can extend medication integrity

• Beyond-use-date (BUD)

• Beyond-use dating is the assignment of an end date for recommended use of a compounded preparation that meets USP guidelines or is supported by independent scientific research

Labeling, Final Check, Dispensing, and Cleanup

• Labeling

  • Patient name

  • Physician name

  • Date of compounding

  • Name of preparation

  • Internal ID or lot number

  • Beyond-use-date

  • Initials of compounding technician and pharmacist

  • Directions for use

  • Any additional requirements

• Final Check by Pharmacist

  • Legally responsible

  • Reviews Master Formulation Record and Compounding Record

  • Physical inspection

  • Initials

• Dispensing and Patient Counseling

  • Alert patient

  • Pharmacist consultation

• Cleanup

  • Clean work area

  • Return ingredients

  • Clean equipment

  • Calibrate balances

  • Adhere to disinfection procedures