Extemporaneous Compounding of Pharmaceutical Products

Compounding

refers to the special preparation of small quantities done by a _of drug products using bulk ingredients that are uniquely tailored or match a patient's needs medically or treat a specific patient's medical condition in response to a prescription written by a licensed practitioner

Compounding

administering the drug to the sight of action in the most effective dosage form available

Compounding

Compounded preparation

Manufacturing

prepare bulk quantities without prescription or medication order

Manufacturing

the mass production of compounded prescription products for resale to pharmacies is regulated by the Food and Drug Administration

Manufacturing

No specific patient in mind when the drug is produced

Manufacturing

Manufactured products

Extemporaneous compounding

the timely preparation of a drug product according to a physician's prescription, a drug formula, or a recipe in which calculated amounts of ingredients are made into a homogenous (uniform) mixture done when certain medical needs of individual patients cannot be met by the use of an approved commercial drug product.

Extemporaneous compounding

preparation, mixing, assembling, packing and labeling of a drug product based on a prescription order from a licensed practitioner for the individual patient.

Minimize error and Maximize prescriber’s intent

What’s the goal of compounding

Appropriateness of the order

In minimizing error and Maximize prescriber’s intent, Pharmacist evaluates the?

Avoid errors and Avoid cross-contamination

In minimizing error and Maximize prescriber’s intent, only 1 preparation should be compounded at a time to?

Reasons for Extemporaneous compounding

a. Unavailable dosage strength and routes of commercial products

b. Dilution of adult doses of medications to Pediatric/Geriatric strengths.

c. Conversion of solid dosage forms to solutions or suspensions.

d. Combination of topical dermatological products not available by the manufacturer.

e. Inactive ingredients of commercial products which may cause allergic reactions in individuals.

f. Compounding associated with specialty practice areas:

✓ veterinary medicine

✓ dermatology

✓ hormone replacement therapy

✓ pain management

✓ hospice

✓ home care

Preparing 10mg capsules from 30 mg tablets

Situation requiring compounding:

• Dose for pediatric patient smaller than commercially available dose

What’s the example?

Patient cannot swallow solid dosage form

Example:

Preparing a suspension from tablets.

What’s the situation requiring compounding

Preparing a thyroid medication for a cat

Situation requiring compounding:

What’s the example?

Dose for veterinary application that is not commercially available

Medication has unpleasant taste

Example:

• Preparing a flavor-masking syrup for a pediatric patient.

Situation requiring compounding?

Oral medication causes adverse effect

Example:

• Preparing a gel for a patient who has had ulcers from oral medication.

  Situation requiring compounding?

Non-sterile Compounding

Sterile Compounding

Types of Extemporaneous Compounding

Non-sterile Compounding

used in the preparation of commercially unavailable drug formulations from bulk ingredients in the community pharmacy for:

▪ Individualized prescriptions for patients

▪ Unique medication requirements

formulation record (master formula)

formulation record

compounding record for each compounded preparation

listing of the ingredients

compounding equipment

instructions for preparing formula

Compounded drugs filed alphabeticall

In Non-Sterile compounding, compounding quality protocols are outlined in USP Chapter 795 and require pharmacies to maintain following:

USP <795>

What USP that defines three categories of non-sterile compounding?

Simple

Moderate

Complex

USP <795> defines three categories of non-

sterile compounding

Degree of difficulty

Scientifically valid information about the stability of the compound

The distinctions of categories of non sterile extemporaneous compounding are based on:

Simple Compounding

include those for which clear data are available, such as information from a manufacturer in the FDA-approved labeling or information detailed in most USP compounding monographs.

Simple Compounding

For example:

• the supplier of an 80-mL Amoxicillin oral suspension, USP, instructs compounders to add 59 mL of water to the bottle to create a final concentration of 250 mg/5 mL. Further information provided may include instructions such as:

• Shake well before using

• Keep bottle tightly closed

• Discard unused portions after 14 days ‹ Refrigeration is preferable but not required

• Those specific details have been researched by the manufacturer and are included in the FDArapproved product labeling

Moderate Compounding

includes either mixing a preparation for which no stability data are available for that particular formulation

Moderate Compounding

or mixing a preparation that requires specialized calculations or procedures that exceed what would be considered simple compounding

Mixture of two topical ingredients when the stability of the mixture is not known

Common example of Moderate Compounding

Morphine Sulfate compounded to suppositories

What are some USP monographs that are moderate compounding

Complex Compounding

includes creating a preparation that requires special training, facilities, equipment, or procedures

making transdermal dosage forms or modified-release preparations

Examples of Complex Compounding

Complex Compounding

Compounders must be aware of the FDA documents on preparations considered “demonstrably difficult” to compound and should follow the outcomes of the FDA’s Pharmacy Compounding Advisory Committee

Sterile Compounding

the process of using an aseptic technique to prepare sterile solutions or solutions that are free of microorganisms for parenteral products or ophthalmic preparations.

Sterile Compounding

most sterile compounding is performed in the “clean room environment.”

Sterile Compounding

rooms are usually positively pressurized to “push” contaminates out and to keep other particles from being pulled in

USP Chapter 797

What USP Chapter that consists of standards for the environment to be considered in the preparation of sterile product

FDAMA of 1997, Extemporaneous compounding

• Made to dispense a product based on an Rx for a specific patient’s needs

• Pharmacists can not compound a copy of a commercially available product

FDAMA of 1997, Extemporaneous compounding

• Pharmacist can not sell his/her product without an Rx

• Can’t advertise the product (i.e. they can advertise only their compounding service but not the product itself)

FDAMA of 1997

Allow pharmacists to compound non-sterile (and/or sterile medications) for an individual patient if these medications meet established USP standards

FDAMA of 1997

• Compounding pharmacies overseen by the board of pharmacy

• Compounding a commercially available product is prohibited

FDAMA of 1997

Compounding pharmacies are not required to follow current good manufacturing practices but only adhere to product labeling or submit drug approval applications

FDAMA of 1997

If a community pharmacy selling products to healthcare professionals or an out-of-state pharmacy must apply for a manufacturing license

enhance patient safety

protect pharmacists from litigation

USP has developed standards to:

Manufactured products

Compounded preparation

BUD

USP according to laws, regulation & Standards

Manufactured products

are prepared off-site by the large-scale drug manufacturer

Compounded preparation

are patient-specific medications prepared on-site

Sources for bulk ingredients

• Decision-based on cost, quality, purity, reputation of the manufacturer

• Pharmaceutical Compounding Centers of America (PCCA) primary source for many large-volume compounding pharmacies

• More than one source recommended in case of shortage, backorder, or product recall.

Beyond-use dating (BUD)

the documentation of the date after which a compounded preparation expires and should no longer be used; initiated when the product is compounded, not when dispensed

14 to 30 days

BUD Estimates for

➢ Refrigerated aqueous solution or suspension:

6 months or less

BUD Estimates for:

Solids such as tablets and Distinction between a capsules (non-aqueous):

take 25% of the remaining expiration date or six months, applies to manufactured which ever is earlier

BUD Estimates for:

Prescription with two or more Beyond-Use Date: a term that applies to compounded active or inactive ingredients:

Beyond-Use Date

a term that applies to compounded preparations

Expiration Date

a term that applies to manufactured products

Class 100 environment

is an environment that has air that contains no more than 100 particles (o.5 microns) or larger in one cubic foot of air.

Laminar flow hoods

What provide the class 100 environment

Horizontal flow hoods

filter air and pass it through a HEPA filter and outward out of the hood

Vertical flow hoods

blow filtered air down towards the surface of the hood

Biological Safety Cabinets

are vertical flow hoods that pulls air through vents in the front and back of the hood to prevent the preparer from receiving this air. It is used to make chemotherapy drugs.

Compounded Preparations guidelines

• should contain between 90% - 110% of labeled active ingredient

• purity and standard quality of ingredients

• compounding methods must be followed from official references

• always keep the formula or master recipe

References for Compounding

Remington’s Pharmaceutical Sciences

Trissel’s Stability of Compounded Formulations

Drug Facts and Comparisons

United States Pharmacopeia

The International Journal of Compounding

Pharmacist

Compounding Equipments guidelines

• the correct equipment is also important when compounding

• calibrated to give correct and accurate measures

• clean before and after use

• suggested equipment, which varies according to the amount of material needed and the type of compounded prescription

Basic Compounding Equipment

• Prescription Balance, Class
  A (required)

• Beakers

• Filter papers

• Graduated cylinders

• Hotplates

• Molds

• Mortar and pestle

• Ointment slab

• Spatulas

• Weighing paper

trained and experienced

Certification of Pharmacy Technicians: Special Certification Training

Compounding Pharmacy Personnel regulations

• Compounding pharmacist _ in extemporaneous compounding

• Pharmacy technicians who work in compounding pharmacies must obtain special certification and training:

Non-sterile Compounding attire must be worn

Compounding Pharmacy Personnel Regulations:

• Clean protective clothing

• Hairnet

• Long lab coat

• Disposable gloves

• Eye goggles

• Face masks

• Gown

• Hand washing - must be done prior to compounding or handling of ingredients

Policies and procedures

Safety data sheets

Master Formulation Records

Compounding Records/Log

Prescription record

DOCUMENTATION for non-sterile compounding

Four key types of documents are required for safe and contemporary compounding concerning documentation

Policies and procedures

should be designed to standardize practices.

Policies and procedures

Standard operating procedures need to be designed and clearly written to ensure accuracy, quality, safety, uniformity in compounding, and accountability.

Safety data sheets (SDSs)

previously known as material _, are required to be available for pharmaceuticals that the drug manufacturer has determined to be hazardous and that are known to be present in the workplace.

Safety data sheets (SDSs)

required medications and chemicals should be available to staff for reference

Master Formula Record (MFR)

➢ “recipe card” is not required when preparing a compound according to the manufacturer’s instructions in the labeling

Compounding Records (CRs)

➢ documents that detail the specific compound dispensed to a particular patient

Prescription record

➢ computer-generated copy of the log, stored and retrievable for future refills

Master Control Record

Documentation for Compounding for non-sterile compounding

Purpose:

A recipe for a compounded preparation

Compounding log

Documentation for Compounding for non-sterile compounding

Purpose:

A printout from the master control log used to prepare a compounded prescription

Master Control Record

Documentation for Compounding for non-sterile compounding

Components:

Drug name

Drug strength

Drug dosage form

Ingredients and quantities

Sequencing and mixing instructions

Beyond-use dating

Storage and labeling information

Compounding log

Documentation for Compounding for non-sterile compounding

Components:

Patient name

Date of compounding

R number

Master Control Record number

Names of ingredients and their expiration dates

Amount needed

Quantity made

Manufacturer

Wholesaler source

NDC number

Assigned lot number

Initials of pharmacist and compounding technician

Magistral Formula

any medicinal product prepared extemporaneously in a pharmacy (and dispensed immediately after preparation and not kept in stock) in accordance with a medical prescription for an individual patient.

Magistral Formula

Official Formula

Types of Formula

Official Formula

any medical product which is prepared in a pharmacy in accordance with the prescriptions of a pharmacopeia.

Official Formula

it is maintained in stock and intended to be supplied directly to the patients served by the pharmacy in question.

Sample master record for an Otic Solution Compound

Calculations in the Compounding Pharmacy

two of the most crucial steps in compounding any pharmaceutical product is the accurate calculation and measurement of the component ingredients of the formulation.

accurate calculation

measurement of the component ingredients of the formulation

two of the most crucial steps in compounding any pharmaceutical product

Calculations in the Compounding Pharmacy

Double check by both the pharmacist and pharmacy technician is strongly recommended to minimize medication errors

Calculations in the Compounding Pharmacy

All measurements and calculations must be documented and reviewed by the pharmacist during the final check of a compounded preparation

Percentage of error

Calculations in the Compounding Pharmacy

• the acceptable range of variation above and below the target measurement

• based on the least weighable quantity of an ingredient

Percentage of error

Calculations in the Compounding Pharmacy

• if a sample is too small, the margin of error may be unacceptable

• compounded nonsterile preparations must have an error range of less than 5

Amount of error/Quantity desired x 100

Formula of Percentage of error

Acetaminophen 2% cream

Furosemide 2mg tab

special considerations of Extemporaneous compounding:

A. Compounding pharmacy makes a unique product doses form for a specific patient,

Give example.

Primary packaging

special considerations of Extemporaneous compounding:

B. __ is important

(light-sensitive drugs or drugs that

bind to the container)

Beyond-use date (BUD)

Special considerations of Extemporaneous compounding:

C. __ on the label of all medications - for stability reasons

Storage temperature

Special considerations of Extemporaneous compounding:

D. __ references with stability data

USP or National Formulary (NF)

Special considerations of Extemporaneous compounding:

E. Ingredient Selection must be __ chemicals preferred

▪ Pharmacists responsible for the selection of chemicals must meet purity & safety standards and should not use drugs withdrawn from the market by the FDA

special considerations of Extemporaneous compounding

A. Compounding pharmacy makes a unique product doses form for a specific patient,

• Acetaminophen 2% cream

• Furosemide 2mg tab

  B. Primary packaging is important (light-sensitive drugs or drugs that bind to the container)

  C. Beyond-use date (BUD) on the label of all medications - for stability reasons

  D. Storage temperature references with stability data

  E. Ingredient Selection must be USP or
  National Formulary (NF) chemicals preferred

• Pharmacists responsible for the selection of chemicals must meet purity & safety standards and should not use drugs withdrawn from the market by the FDA

Sources for chemicals and drugs

Equipment

Location of compounding area/ Environment

Source of information

Pharmacy personnel

Basic Requirements for Compounding

Sources for chemicals and drugs

pharmacists must obtain small quantities of the appropriate chemicals or drugs from wholesalers.

Equipment

• the correct equipment is also important when compounding

• Clean, functioning optimally

Location of compounding area/ Environment

many pharmacies actively involved in compounding have dedicated a separate area in the pharmacy to this process.

Source of information

• pharmacy textbooks (USP/ NF, Remington) Journals, manufacturer's drug product

• information inserts