1C.Extemporaneous compounding

compounding

refers to the special preparation of small quantities done by a compounding pharmacist 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

“Minimize error and Maximize prescriber’s intent”

Goal of Compounding

pharmacist

who evaluates the appropriateness of the order ?

✓ avoid errors

✓ avoid cross-contamination

Only 1 preparation should be compounded at a time to:

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:

reasons for extemporaneous compounding

✓ veterinary medicine

✓ dermatology

✓ hormone replacement therapy

✓ pain management

✓ hospice

✓ home care

Compounding associated with specialty practice areas:

1. dose for pediatric patients smaller than commercially available dose

2. patient cannot swallow solid dosage form

3. dose for veterinary application that is not commercially available’

4. medication has unpleasant taste

5. oral medication has adverse effect

what are the situations requiring compounding?

dose for pediatric patients smaller than commercially available dose

ex. preparing 10mg capsules from 30 mg tablets

patient cannot swallow solid dosage form

ex. preparing a suspension from tablets

dose for veterinary application that is not commercially available

ex. preparing a thyroid medication for a cat

medication has unpleasant taste

ex. preparing a flavor-mask syrup for a pediatric patient

oral medication causes adverse effect

ex. preparing a gel for a patient who has has ulcers from oral medication

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 patient

Unique medication requirements

▪ formulation record (master formula)

▪ formulation record - an individual record (like a recipe)

▪ compounding record for each compounded preparation

▪ listing of the ingredients

▪ compounding equipment

▪ instructions for preparing formula

▪ Compounded drugs filed alphabetically

compounding quality protocols are outlined in USP Chapter 795 and require pharmacies to maintain the following:

simple

moderate

complex

USP <795> defines three categories of nonsterile compounding:

degree of difficulty

the availability of scientifically valid information about the stability of the compound.

non-sterile extemporaneous compounding distinctions 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.

✓ 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 FDA-approved product labeling

Further information provided in simple compouding may include instructions such as:

moderate compounding

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

moderate compounding

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

moderate compounding

A common example is a mixture of two topical ingredients when the stability of the mixture is not known.

moderate compounding

Some USP monographs, such as Morphine Sulfate Compounded to Suppositories

complex compounding

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

complex compounding

Examples include making transdermal dosage forms or modified-release preparations

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.

“clean room environment”

most sterile compounding is performed in the __

sterile compounding

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

USP Chapter 797

consists of standards for the environment to be considered in the preparation of sterile products

Food & Drug Administration Modernization Act of 1997

Regulation required

United States Pharmacopeia

standard required

Laws, Regulations and Standards

Pharmacy must agree to meet all standards for sterile and nonsterile compounding

Laws, Regulations and Standards

Includes monthly or quarterly spot check

Laws, Regulations and Standards

Random product sent to an outside lab for analysis

Laws, Regulations and Standards

Product must be +/-2% of potency

Laws, Regulations and Standards

Any corrective action must be documented and dated by the pharmacist

▪ 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

▪ 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

According to the FDAMA of 1997, Extemporaneous compounding is.....

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

FDAMA of 1997

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:

1. Manufactured products

2. Compounded preparation

3. Sources for bulk ingredients

4. Beyond-use dating (BUD)

under USP

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

shortage, backorder, or product recall

More than one source recommended in case of -

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

Refrigerated aqueous solution or suspension

6 months or less

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

take 25% of the remaining expiration date or six months, whichever is earlier

Prescription with two or more active or inactive ingredients:

Beyond-Use Date

a term that applies to compounded preparations

Expiration Date

a term that applies to manufactured products

❖ highly clean and sanitized

❖ Adequate space and storage area

❖ Orderly placement & storage of equipment and ingredients

❖ Dispensing bench containing different containers and ingredients

❖ Controlled temperature/ lighting

❖ Sink with hot & cold running water essential for hand washing & equipment cleaning

❖ must have an eyewash station

❖ physically separated from the dispensing area

compounding working environment guidelines

class 100 environment

is environment that has air that contains no more than 100 particles (0.5 microns) or larger in a cubic foot of air

laminar flow hoods

provides the environment

horizontal flow hoods

filters air and pass it through a HEPA FILTER and outward of the hood

vertical flow hoods

blow filtered air down towards the surface of the hood

Biological Safety Cabinets

are vertical flow hood that pulls air through vents in the front and back of the hood to prevent the preparer from receiving this air

Biological Safety Cabinets

it is used to make chemotherapy drugs

➢ 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

compounded Preparations guidelines

▪ Remington’s Pharmaceutical Sciences

▪ Trissel’s Stability of Compounded Formulations

▪ Drug Facts and Comparisons

▪ United States Pharmacopeia

▪ The International Journal of Compounding Pharmacists

References for Compoundings

➢ 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

Compounding Equipments guidelines

▪ Prescription Balance, Class A (required)

▪ Beakers

▪ Filter papers

▪ Graduated cylinders

▪ Hotplates

▪ Molds

▪ Mortar and pestle

▪ Ointment slab

▪ Spatulas

▪ Weighing paper

Basic Compounding Equipment

Compounding pharmacist trained and experienced in extemporaneous compounding

Compounding Pharmacy Personnel regulations

Certification of Pharmacy Technicians: Special Certification Training

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

▪ 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

Non-sterile Compounding attire must be worn:

✓ are appropriate for the patient

✓ have acceptable strength, quality, and purity

✓ are prepared in accordance with the prescription or medication order

✓ comply with requirements or restrictions in federal or state laws or regulations

✓ follow the Master Formulation Record for those compounds that require it

✓ are packaged and labeled to conform with policies and safe practices

Pharmacists and pharmacy technicians who perform compounding must ensure that the preparations they mix:

To protect the processes established and to keep patients safe

Work practices such as hand hygiene, proper garbing, meticulous technique, and the ability to perform the required procedures are essential

❖Policies and procedures

❖Safety data sheets

❖Master Formulation Records

❖Compounding Records/Log

❖Prescription record

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

Policies and procedures

should be designed to standardize practices.

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 safety data sheets, 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

purpose: a recipe for compounded preparation

compounding log

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

Drug name

Drug strength

Drug dosage form

Ingredients and quantities

Sequencing and mixing instructions

Beyond-use dating

Amount needed

Storage and labeling

information

components of master control record

Patient name

Date of compounding

Rx number

Master Control Record number

Sequencing and mixing

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

components of compounding log

magistral formula

official formula

types of formula

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.

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

accurate calculation and measurement of the component ingredients of the formulation

two of the most crucial steps in compounding any pharmaceutical product is the

calculation in compounding pharmacy

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

measurements and calculations

All ____ must be documented and reviewed by the pharmacist during the preparation