The New Way of Talking about Quality: The PCCA Standard

Wed, 15 May 2019 14:37:47 GMT

“Quality” is an especially important word in pharmacy compounding. This is because the quality of everything from the chemicals and the base to the formula and all that supports it factor into the final compounded medication that can change a life, or even save it. The best clinical outcomes that a compounding pharmacy can deliver start with the best ingredients and the science behind them.

What quality actually means, however, is often left unexplained. But since it is so important in our industry, we decided to help the pharmacies who rely on PCCA for products and support by clarifying what we mean when we talk about quality.

When we talk about quality — whether we’re referring to an active pharmaceutical ingredient, a compounding base, formulas, research, services and more — we mean that it meets The PCCA Standard, our commitment to go above and beyond what is required, because lives depend on a job well done.

The PCCA Standard is every time we ask chemical manufacturers more questions than we have to. It’s when we reject manufacturers who don’t meet our criteria above and beyond regulatory requirements. The PCCA Standard is not just rigorously assessing manufacturers, but subjecting every lot of every chemical we receive to over 20 checks, tests and verifications on top of that. And it’s rejecting up to 250 lots of chemicals every year because they don’t measure up to the quality we demand for the sake of your pharmacy and your patients.

The PCCA Standard is creating industry-defining bases that address tomorrow’s compounding needs today. And it’s producing those bases — lot after lot — according to current good manufacturing practices, even though regulations don’t require us to. The PCCA Standard is also having the most comprehensive, well-supported formula database in the industry, with over 9,600 formulas. And it’s using the latest scientific methods to establish extended beyond-use dates for our most popular formulas.

Above all, The PCCA Standard is our commitment to making the hard choices about the products and support we provide you and, ultimately, your patients — making those hard choices so that you don’t have to. We do all of this because “quality” in pharmacy compounding is about more than a product; it’s about a pharmacist, a physician and a patient — every single time.

This is just a glimpse at The PCCA Standard. To really see the values and processes that we’re proud to put our name on every single day, visit thepccastandard.com.

Why Water Activity Matters in Pharmacy Compounding

Mon, 18 Feb 2019 17:34:42 GMT

By Daniel Banov, RPh, MS, PCCA Director of Research and Development

This article was updated: 08/31/2020

Water represents the largest component in most compounds, pharmaceuticals, cosmetics and foods. In pharmacy compounding, any preparation containing water requires preservation against microbial contamination and growth in order to increase its beyond-use date (BUD) and to ensure patient safety. However, anhydrous compounded preparations, which contain no water or a negligible amount, can have longer BUDs by default because the lack of water reduces the risk of microbial growth and chemical degradation. This is why the concept of water activity in various products is becoming increasingly important in the pharmacy compounding world.

Water Activity and Water Content
Water activity (Aw) is a concept introduced in the 1920s by Levis and Randall.¹ It is a measure of water in a substance that is available to react with or attach itself to a material, and it ranges from 0.03–1.0. This available water, or free water, can be responsible for the growth of molds, yeasts and bacteria as well as toxin production, or it may participate in chemical or biochemical reactions. Most topical products have water activity above 0.85, which is sufficient to support the growth of bacteria, yeasts, and molds, and accounts for the need for preservatives.^2,3,4

Water activity is different from water content (or moisture content), which is a measure of the total amount of moisture in a material and is usually expressed as a percentage of the total amount (% of total weight). The table below explains the important differences between them.⁴

The Differences Between Water Content and Water Activity
Water (Moisture) Content	Water Activity
Total amount of water present in a product	The water that is available for reactions in a product
Measured by initial weight of the sample	Independent of initial weight of the sample
Not a reliable indicator of microbial growth or chemical degradation potential	Good indicator of microbial growth or chemical degradation potential

Water Activity and Microorganism Growth

While temperature, pH, and several other factors can influence whether an organism will grow in a product and the rate at which it will grow, water activity is often the most important factor. Bacteria usually require at least Aw 0.75, whereas yeast and mold require at least Aw 0.61. The water activity level that limits the growth of the vast majority of pathogenic microorganisms is Aw 0.60, so if a product has Aw below 0.60, it is considered anhydrous. The table below shows the water-activity levels necessary for microbial growth.^2,5,6

Minimum Aw Values for Growth of Microorganisms
Organism Group	Water Activity (Aw)
Gram-negative bacteria	0.90
Gram-positive bacteria	0.75
Yeast	0.61
Molds	0.61

However, it is important to understand that the microbiological risk cannot be based on only one parameter. Ultimately, it depends on a multifactor analysis that takes into account physicochemical parameters linked to the product (pH, package, bioburden, chemical quality, compounding environment).^3,5

Water Activity and Chemical Reactivity

Water activity influences not only microbial growth but also chemical and enzymatic reactivity. It influences non-enzymatic browning, lipid oxidization, degradation of vitamins, enzymatic reactions and protein denaturation. Typically, when water activity is lower, the rate of chemical degradative reactions decreases. Figure 1 offers a visual representation of the relationship between reaction rates and water activity.³

Figure 1: Water Activity - Stability Diagram (adapted from Decagon)³

What Water Activity Means for Compounding Pharmacies

This means that water activity is crucial to understanding BUDs. Lower water activity in compounded preparations allows compounders to assign longer BUDs to them by default, which is reflected in USP guidelines. For compounders, this can lower operating costs because they do not have to pay for costly stability studies to assign a longer BUD, and it can also increase operational efficiency when compounders need to make anticipatory batches.

For patients, compounded medications with longer BUDs mean that they do not have to refill their prescriptions as often, so they are more convenient and efficient for them as well.

The best way to ensure low water activity in compounds and get the longest default BUDs is to use anhydrous bases and ingredients. Fortunately, PCCA offers a wide range of anhydrous bases.

PCCA Bases with Low Water Activity

PCCA carries a selection of anhydrous bases that have low water activity:

PracaSil®-Plus is an innovative topical base developed for customized medications prescribed to improve the appearance of scars, including keloid and acne scars
RDT-Plus™ is a powder base for compounding rapid dissolve tablets
Anhydrous Lipoderm® is the anhydrous version of the industry-standard transdermal base Lipoderm
Polyglycol Troche™ is a versatile troche base with sweetener and suspending agents already added
Gelatin™ is an elegant gelatin base for compounding troches
LoxaSperse® is an innovative powder excipient base created for compounding with active ingredients used for nebulizations and irrigations
XyliFos® is an excipient base developed to be used in combination with LoxaSperse to maximize its solubilizing and dispersing properties and antimicrobial synergy
LoxOral® is an all-in-one capsule excipient base
Plasticized™ is a soft, elegant polyethylene and mineral oil gel base commonly used for topical and oral preparations
Fixed Oil Suspension Vehicle is an oil-based (anhydrous) oral suspending vehicle allowing compounders to simply add active ingredients, sweetener and flavor as prescribed to suit the patient’s needs
MBK™ (Fatty Acid) is a stable base with a low irritation profile and low melting point (body temperature), making it ideal for patient-specific suppositories

In recent years,, PCCA has also launched new bases characterized by low water activity (Aw < 0.6) in order to improve stability and to reduce microbial growth and chemical degradation in the corresponding compounded medications:

PermE8™ Anhydrous Gel is an anhydrous transdermal base that can hold multiple drugs, including those in salt form, and deliver them through the skin comparably to Lipoderm
NataTroche™ is a troche base made with natural ingredients that does an exceptional job at masking the bitterness of many active ingredients, such as progesterone
W06™ Anhydrous Topical Gel is an anhydrous topical base that was designed to be used in dermatologic and cosmetic formulations and can accommodate the use of many APIs, especially the more challenging ones like hydroquinone and ascorbic acid which easily oxidize in formulations with higher water activity
VersaBase® Anhydrous HRT is the pharmacy compounding industry’s first proprietary anhydrous base developed specifically to deliver female bioidentical hormones through the skin. It is also the latest addition to the VersaBase family of compounding bases that has provided patients with much-needed customized medication options for over a decade

Daniel Banov, RPh, MS, PCCA Director of Research and Development, has over 20 years of hands-on experience in pre-formulation, formulation and reformulation of a variety of dosage forms. He has extensively worked on developing novel techniques for skin-permeation enhancement. Daniel currently has 17 granted U.S. patents and many others pending. Before joining the PCCA team, Daniel was the Director of Fórmula Médica Compounding Pharmacy in São Paulo, Brazil, and was a university teacher and a cosmetic developer and consultant for physicians, spas and aestheticians. He also is the founder of the Anti-aging Society in Brazil.

A version of this article was originally published in the winter 2019 issue of the Apothagram, PCCA’s members-only magazine.

References

Sandulachi, E. (2012). Water activity concept and its role in food preservation. Meridian Engineering, 2012(4), 40–48.
International Cooperation on Cosmetics Regulation. (n.d.). General and technical frequently asked questions (FAQs) on preservatives in cosmetics. Retrieved from https://ec.europa.eu/docsroom/documents/15281/attachments/1/translations/en/renditions/native
Decagon Devices. (2006). Fundamentals of water activity. Retrieved from https://www.graintec.com.au/media/12856/Fundamentals.pdf
Gatenby, A. (2013). Moisture content and water activity - What are they? [web log post]. Retrieved from https://www.cscscientific.com/csc-cientific-blog/moisture-content-and-water-activity-what-are-they
Berthele, H., Sella, O., Lavarde, M., Mielcarek, C., Pense-Lheritier, A. M., & Pirnay, S. (2014). Determination of the influence of factors (ethanol, pH and aw) on the preservation of cosmetics using experimental design. International Journal of Cosmetic Science, 36(1), 54–61. https://doi.org/10.1111/ics.12094
Steinberg, D. C. (2013). Water activity. Cosmetics & Toiletries. Retrieved from https://www.cosmeticsandtoiletries.com/research/methodsprocesses/premiumWater-Activity.html

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.

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The New Way of Talking about Quality: The PCCA Standard

Why Water Activity Matters in Pharmacy Compounding