"Better Quality through Quality Testing"

Tools we provide

Compounders need a variety of tools in order to produce safe, high quality prescriptions that meet regulatory requirements.   We can provide some of those tools to help you succeed.

 

The USP as well as local Boards of Pharmacy are concerned that compounded prescriptions are of correct potency and purity to accomplish their intended goal without doing harm.  Our experience has shown that despite correct formulation worksheets, accurate weighings and measurements, and documenting procedures, the preparations may still not be as intended.  These are often due to inadvertent mislabeling of containers and medication vials, incomplete blending or trituration, breakdown of the actives, unknown impurities in the actives, accidental double weighing of the active, failure to include the active, misreading of labels and adding the wrong form of the active, failure to account for % water in the active, and more.  The only way to know if such problems exist is through testing, especially through the use of an independent outside laboratory.
To err is human, but not testing, is risky!

The USP has much to say in this regard.  “ Responsibility of the compounder (is to assure that). . .compounded preparations are of acceptable strength, quality, and purity.”  (See below for other quotations from the USP)
We have had extensive experience in performing potency assays on all kinds of formulations and dosage forms, from capsules to creams and gels, injectables to IV solutions,to  troches, lozenges, suppositories, pellets, and more.  Each sample you submit is individually evaluated for the best means of analysis.  The assay is then performed in a manner which assures the results will be accurate.  Our potency assays are usually completed within 2-3 days.
Our potency testing is most often carried out using Ultra High Performance Liquid Chromatography, the most advanced analytical technique available, and one which meets or exceeds regulatory requirements.

 

Below, are quotations from the USP which we feel are compelling reasons for potency and sterility testing.
Responsibility of the Compounder
• insure that “the quality is built into the compounded preparation of the product.”
“ assure ingredients used in compounding have their expected identity, quality and purity.”
• make sure “compounded preparations are of acceptable strength, quality and purity.”
• determine that “critical processes are validated to insure that procedures, when used, will consistently result in the expected qualities in the finished preparation.”
“ assure that processes are always carried out as intended and specified and are under control.”

 

Stability Testing

Stability testing is the testing of the entire package: active ingredient(s), excipients, and container.  Normally accepted beyond-use dating (BUD) is provided in the USP and elsewhere in the literature.  When it is believed that the standard dating of a formulation can be exceeded, and extended BUD is desired, allowance for this is provided in the USP if there is solid scientific data supporting the new limit.  We can provide the data required to meet these requirements.
Samples which are submitted to us for stability testing must be in the same formulation and packaging which are intended for use, with directions for storage (lighting conditions and temperature).

Stability-Over-Time Testing

We can perform stability testing to help you determine the best BUD of your formulations.  Typically, for compounders, samples are submitted in their usual containers in a quantity sufficient for the duration of the study.  When received, we immediately test the potency, as well as sterility, fungal, and endotoxin (where appropriate), to establish baseline values.  Samples are  then stored according to instructions, at room temperature, refrigeration, freezer, or even body temperature conditions.  At predetermined time points, samples are pulled out of storage and again tested until the potency has declined to its allowable limit.  At this point it is typical to again test sterility, fungal, and perhaps endotoxin to assure the integrity of the product has been maintained.  Because we use UltraHigh Performance Liquid Chromatographs equipped with PhotoDiode Array and/or Mass Spectrometer detectors for these assays, our analytical results are normally free from interferences and are extremely accurate.

 

Stability Studies Involving Stability Indicating Assay Methods

Increasingly, compounders are being required to follow the same stability study protocols as the major pharmaceutical manufacturers, in that they should be performed using “stability indicating assay” methods.  This differs from “stability over time” studies in that each sample is forcibly degraded with acid, base, heat, light, and oxidizing agent in an effort to generate all possible break-down products before the study begins.  Stability indicating assay methods are then developed with these degraded samples which will assure none of the break-down components will interfere with the active(s) during the course of the actual study. Samples are then tested at predetermined time points until potency has declined to its allowable limit.  These assays are also carried out with UltraHigh Performance Liquid Chromatographs equipped with PhotoDiode Array and/or Mass Spectrometer detectors which offer great accuracy and specificity.

 

Below, are quotations from the USP which pertain to stability testing
Stability Criteria and Beyond-Use Dating
“Appropriate stability is performed or determined from the literature for establishing reliable beyond-use dating (BUD) to insure that the finished preparations have their expected potency, purity, quality, and characteristics, at least until the labeled BUD.”
“Where the manufactured drug product is the source of the active ingredient, the BUD is not later than 25% of the time remaining until the products’ expiration date or 6 months, whichever is earlier.”
“For water containing formulations, (prepared from ingredients in solid form) the BUD is not later than 14 days for liquid preparations when stored at cold temperatures between 2 and 8 (36 and 46F).”
“For all other formulations the BUD is not later than the extended duration of therapy or 30 days, whichever is earlier.”
“ These BUD limits may be exceeded when there is supporting valid scientific stability information that is directly applicable to the specific preparation (i.e. the same drug, concentration range, pH, excipients, vehicle, water content, etc.)”

 

Bacterial Endotoxin Testing
Bacterial endotoxins are the by-product of bacteria.  They are very difficult to remove from surfaces.  Filtration, autoclaving, and dry heat will not remove or destroy them.  Consequently, they can be easily and inadvertently introduced into sterile preparations.  They are highly toxic and even deadly.  The only way to comply with USP Chapter <85> and <451> manditory allowable endotoxin levels is by testing.  The test we use takes one hour, is usually done immediately upon receipt of the sample, and you are notified of the results the same day. Please provide ml/wt, (for humans kg of patient’s weight/ml to be administered in 1 hr.) and the route of administration per USP <85>.

Sterility Testing
“Assurance of sterility in a compounded preparation is mandatory.”  USP <795> 
Injectables, parenteral products, interthecal preparations and powders for specific uses must be demonstratably sterile.  The USP requires maintaining and validating the sterility of these preparations during formulation and packaging.
The responsibility of the compounder in . . . “ Critical processes are validated to insure that procedures, when used, will consistently result in the expected qualities in the finished preparation.”
The only way to demonstrate that the USP requirements have been met is through testing.  Ideally, each sample should be tested.  Practically, random samples of each batch should be tested.
The USP also sets forth guidelines for testing.  We go above and beyong those requirements.  Sterility testing looks for any microbial growth in the samples being tested.  It usually takes two weeks to complete a sterility test.  After one week we send you a Preliminary Report so you’ll know how things are progressing.  If we observe any growth during the two weeks you will be notified at once. Please provide the correct number of samples based on the batch size per USP <71> requirements.

 

Below, are quotations from the USP which we feel are compelling reasons for potency and sterility testing.
Responsibility of the Compounder
• insure that “the quality is built into the compounded preparation of the product.”
“ assure ingredients used in compounding have their expected identity, quality and purity.”
• make sure “compounded preparations are of acceptable strength, quality and purity.”
• determine that “critical processes are validated to insure that procedures, when used, will consistently result in the expected qualities in the finished preparation.”
“ assure that processes are always carried out as intended and specified and are under control.”

 

Fungal Testing
Fungi are slow-growing and difficult to detect in liquid medias.  Sterile preparations must be tested specifically for fungi to prevent fungal infections when administering medications.  Since molds, fungi, and sporulations are present everywhere, no part of the country is immune to the possible contaminant.  The test takes two weeks to complete and you will be notified at once if any growth is observed.