Liz Fredrickson is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University College of Pharmacy. She serves as the Director of Instructional Labs and is the course director for the Basic Pharmaceutics Lab and Parenteral Products and Parenteral Products Lab courses.


Topic Overview


Assigning appropriate beyond-use dates is an important part of the nonsterile compounding process. Using their knowledge of stability and the United States Pharmacopeia (USP) standards, pharmacists can assign beyond-use dates to compounded nonsterile preparations that will ensure product integrity and safety throughout the usage and storage period. This course will assist pharmacy personnel in understanding parameters to consider when determining beyond-use dates for compounded nonsterile preparations and will provide recommendations for assigning appropriate beyond-use dates for these types of preparations. USP General Chapter <795> guidelines will be reviewed.


Accreditation Statement:


image, LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.


Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist 0669-0000-22-106-H07-P

Pharmacy Technician 0669-0000-22-107-H07-T

Credits: 1 hour of continuing education credit


Type of Activity: Knowledge


Media: Internet Fee Information: $4.99


Estimated time to complete activity: 1 hour, including Course Test and course evaluation


Release Date: December 21, 2022 Expiration Date: December 21, 2025


Target Audience: This educational activity is for pharmacists.


How to Earn Credit: From December 21, 2022, through December 21, 2025, participants must:


Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)


Learning Objectives: Upon completion of this educational activity, participants should be able to:


Describe factors that can affect the stability of compounded nonsterile preparations

Explain water activity and its importance in determining beyond-use dates for compounded nonsterile preparations

Assign appropriate beyond-use dates to compounded nonsterile preparations

Recall considerations for extending beyond-use dates for compounded nonsterile preparations



The following individuals were involved in the development of this activity: Liz Fredrickson, PharmD, BCPS, and Susan DePasquale, MSN, PMHNP-BC. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.


ⓒ LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of LLC.



Preparing safe, effective, and quality compounded nonsterile preparations requires many essential steps, one of which is assigning an appropriate beyond-use date. This requirement lets patients know when their medication can no longer be safely used. Using their knowledge of stability and United States Pharmacopeia standards, pharmacists can assign beyond- use dates to compounded nonsterile preparations that will ensure product integrity and safety throughout the usage and storage period. This course will assist pharmacy personnel in understanding parameters to consider when determining beyond-use dates for compounded nonsterile preparations and will provide recommendations for assigning appropriate beyond-use dates for these types of preparations. United States Pharmacopeia, General Chapter

<795>, will be reviewed in this context.


Beyond-use Date Basics


The term beyond-use date (BUD) refers to the date (or hour and date) after which a compounded nonsterile preparation (CNSP) cannot be used and must be discarded.1 Guidelines for assigning beyond-use dates are provided by the United States Pharmacopeia (USP).1 The BUD can be calculated in terms of hours, days, or months.1 Before learning more about what a BUD is, it can be helpful to understand what it is not. The most important distinction is recognizing the differences between a BUD and an expiration date. These terms are compared in Table 1. An expiration date is defined as the time during which a conventionally manufactured product, active pharmaceutical ingredient (API), or added substance can be expected to meet the requirements of a compendial monograph or maintain expected quality if it is kept under the prescribed storage conditions.1 An expiration date limits the time during which manufactured products can be dispensed or used.1 Beyond- use dates are typically much shorter than expiration dates and do not require the extensive testing needed for expiration dating.1

Table 1. Comparison of Beyond-use Dates and Expiration Dates1,2

 Beyond-use DateExpiration Date
DefinitionThe date (or hour and date) after which a CNSP cannot be used

The time during which a conventionally manufactured product, active pharmaceutical ingredient (API), or added substance can be expected to meet the requirements of a compendial monograph or maintain expected quality, if it is kept under the prescribed storage


Assigned byAssigned by compounding personnelAssigned by the manufacturer

Determined using stability data and USP Chapter

<795> guidelines

Determined using extensive testing


The Importance of Beyond-Use Dates


Beyond-use dates are important for both compounding personnel and patients. Once the BUD has passed, the product becomes at risk for physical and chemical degradation, reduced integrity of the container-closure system, and microbial contamination.1 Patient safety should always guide the process of preparing nonsterile compounds, and this includes the assignment of beyond-use dates. However, while choosing a less conservative BUD or extending a BUD may seem convenient or be seen as a method by which to reduce waste, inappropriately assigning BUDs can also lead to potential patient harm. There are some valid methods by which to extend beyond-use dates of CNSPs, and these will be discussed later in this course.


Regulatory Oversight


A BUD can be thought of as a risk assignment determined by using the most current and evidence-based information available.3 Various regulatory

organizations provide oversight for CNSP beyond-use dating, including the Centers for Medicare and Medicaid Services (CMS) and The Joint Commission (TJC).3 The American Society of Health-System Pharmacists (ASHP) published “The Pharmacist Guide to Assigning a Beyond-use Date to a Compounded Sterile or Nonsterile Preparation,” which includes a useful table detailing stances on beyond-use dating among various organizations (Table 2).3 Of these organizations, the most influential is the United States Pharmacopeia, and many other organizations refer to these standards.1,3 For example, the

U.S. Food and Drug Administration (FDA) refers to USP recommendations regarding the assignment of BUD.3


Table 2. Organizational Stances on Beyond-use Dating3

OrganizationRelevance of Organization to BUDStance on BUD
American Society of Health-System Pharmacists (ASHP)ASHP is the largest pharmacy organization in the worldThe ASHP Guidelines on Compounding Sterile Preparations references USP standards

Centers for Medicare and

Medicaid Services (CMS)

CMS is a US federal agency that sets minimum standards

of care (for both

Per general references, “BUD is to be based on information provided by the manufacturer, whenever such information is available.”
 patients and is
 intended to set the
 bar for high quality
 and value.
 Non-compliance with
 CMS minimum
 standards would
 make health
 systems ineligible
 for reimbursement
 and therefore CMS
 works with other
 organizations to
 ensure compliance
 with minimum standards. 

Det Norse Veritas (DNV),

healthcare sector

This is a non-profit, independent, non- governmental organization that aligns with CMS standards, but may also exceed federal standards to achieve the highest safety, quality, and value standards.Aligned with CMS
Healthcare Facilities Accreditation Program (HFAP)

A non-profit, independent, non- governmental organization that aligns with CMS standards, but may also exceed federal standards to achieve the highest safety, quality, and value standards.

Recognized as a CMS deeming authority.a

Aligned with CMS
National Association of Boards of Pharmacy (NABP)NABP provides a platform for contact information and web links for individual state boards of pharmacy.

State board of pharmacies vary as to enforcement of BUD requirements and may be more

stringent than USP standards.

Joint Commission (JC)

JC is a non-profit, independent, non- governmental organization that

aligns with CMS

Aligned with CMS.

General reference to USP standards

 standards, but may also exceed federal standards to achieve the highest safety, quality, and value standards. 

United States Food and Drug

Administration (FDA)

FDA is a federal

regulatory body that includes medications

Provides compounding-related guidance mainly targeted to outsourcing facilities

Sets expiration date expectations that drug manufacturers must comply with

Defers to USP guidance for BUD assignment

 (both prescription
 and over the
 counter) in its

aOrganizations who meet the standards of this accreditation body automatically qualify for the standards set forth by CMS for reimbursement.


USP standards are divided into chapters. Chapter <795> of the USP, entitled “Pharmaceutical Compounding—Nonsterile Preparations, describes standards to be followed for the preparation of CNSPs for humans and animals.1 These are considered minimum practice guidelines when compounding nonsterile preparations.1 Notably, guidance from USP is descriptive rather than prescriptive or exhaustive. Thus, it is up to compounding personnel to implement these measures using the utmost professional judgment.1,4 The types of CNSPs subject to USP General Chapter

<795> requirements include the following:


Solid oral preparations

Liquid oral preparations

Rectal preparations

Vaginal preparations

Topical preparations (i.e., creams, gels, and ointments)

Nasal and sinus preparations intended for local application (i.e., nasal sprays and nasal irrigation)

Otic preparations (excluding use in perforated eardrums)


The requirements in the chapter must be followed to minimize harm, including death, to human and animal patients that could result from the following:1


Excessive microbial contamination

Variability from the intended strength of correct ingredients

Physical and chemical incompatibilities

Chemical and physical contaminants

Use of ingredients of inappropriate quality


Previously, USP, Chapter 795, had not been updated since 2014. The following years included rounds of revisions and a public comment period, with the publication of the most recent updates to USP <795> on November 1, 2022,1 These revised guidelines include stakeholder input and scientific and technological advances and include extensive updates to beyond-use dating.1,5 United States Pharmacopeia, General Chapter <795>, is considered an enforceable chapter, and such enforcement is the responsibility of state boards of pharmacy, which may choose to require even more stringent beyond-use dating requirements.1,4 Compounding personnel should always refer to and follow compliance requirements of their specific state board of pharmacy or the board of pharmacy for states in which they are licensed.1,4


Factors Impacting Beyond-Use Dates


It is recommended to assign beyond-use dates to CNSPs in a conservative manner; this helps ensure the product will remain safe and effective during use and storage and will minimize the chance of contamination or degradation. In the process of establishing a beyond-use date, there are numerous factors to consider, including the following:1


The chemical and physical stability properties of the active pharmaceutical ingredient (API)

The chemical and physical stability of any added substances (excipients) in the preparation

The compatibility of the container closure system with the finished preparation

The degradation of the container closure system, which can lead to a reduction in the integrity of the CNSP

The potential for microbial growth in the CNSP

Any significant deviations from essential compounding steps and procedures, as changes to essential compounding steps may have an impact on the stability of the formulation


Stability Considerations


Compounding personnel cannot assume with certainty that the API within a preparation will maintain its strength and purity solely by following USP 795 guidelines, and thus stability is a key consideration in determining the BUD of a product.4 Stability is defined as the extent to which a product retains the same properties and characteristics it possessed at the time it was manufactured throughout its time of storage and use.6,7 United States Pharmacopeia, Chapter <1191> - Stability Considerations in Dispensing Practice, provides useful information on stability considerations for compounding personnel.7 United States Pharmacopeia recognizes five general types of stability with associated criteria for acceptable levels of stability, including the following:8


Chemical: each API retains its physical and chemical integrity and labeled potency

Physical: the original physical properties are retained (includes appearance, palatability, uniformity)

Microbiological: sterility or resistance to microbial growth is retained

Therapeutic: therapeutic effect remains unchanged

Toxicological: no significant increase in toxicity occurs

Many factors can affect the stability of a preparation. These include temperature, pH, light, oxygen, moisture, particle size, and changes in formulation ingredients.




Temperature has the potential to affect heat-sensitive APIs at many points in the compounding process. Increases in temperature have the ability to increase the speed of chemical reactions.7 In general, for every 10-degree increase in temperature, the rate of drug degradation will increase exponentially.7 United States Pharmacopeia, Chapter <1191> includes an example of how the shelf-life of a hydrolyzable drug exposed to a 20-degree increase in temperature could decrease from one-fourth to one-twenty-fifth its shelf life under refrigeration.7 While this is an extreme example, it highlights the important role of heat in a drug’s stability.




pH is another major factor to consider when determining the stability of a product. For any CNSP, personnel should determine the appropriate pH to maintain stability.7 As the pH of a solution is decreased or increased over a specific range of pH values, the degradation of many drugs will either accelerate or decelerate exponentially. pH buffer systems (a weak acid or base and its salt) can be used to keep pH within the desired range and minimize degradation.7




Light can affect CNSP stability by causing photodegradation via photo- oxidation and photolysis.6 In cases where light-sensitive APIs are used, packaging should be light-resistant.7 Interestingly, some medications are light-sensitive under different conditions but not others. For example, a drug may be light-sensitive when in water but not when generally exposed to light.6



Oxygen can cause product degradation via oxidation.7 Compounds that are likely to oxidize include those with conjugated dienes, heterocyclic aromatic rings, nitrite derivatives, and aldehydes (for example, flavorings).7 Products that result from oxidation typically lack therapeutic activity.7 Oxidation can be noted when the product elicits an unpleasant smell or taste, becomes discolored, or precipitates.6 There may be instances when compounding personnel are unaware oxidation has occurred. To minimize the risk of oxidation, headspace within a container should be decreased as much as possible.6 Compounding personnel can also add antioxidants to certain CNSPs to minimize or slow the oxidative process that may occur when the API or excipients are exposed to oxygen.6 Which antioxidant is best will depend on factors such as solubility, compatibility, and chemical and physical stability.6 Another technique is to decrease the amount of air entrapped within the preparation.6 To do this, personnel should be cautious not to foam or whip products during mixing.6




Moisture or humidity can cause hydrolysis reactions.6,7 Beta-lactams and esters are types of chemical bonds that are likely to hydrolyze when in the presence of water.7 Compounding personnel should be aware of medications that contain these types of bonds (such as aspirin) and work to mitigate the impact of hydrolysis.7 Helpful strategies include keeping the environment dry and packaging products with desiccant packets to assist with minimizing the risk of moisture accumulation.6


Particle Size


Particle size can also play a role in instability.6 In general, the smaller the particle size, the greater the chance the product may react.6 To mitigate this problem, compounding personnel can try to use a larger particle size when compounding powders and capsules.6

Formulation Changes


Formulation changes may alter the stability of a preparation, and any change in ingredients will generally warrant a new stability study or the obtainment of new stability information.4 For example, if compounding personnel reference a study that used a specific base with the active pharmaceutical ingredient and they wish to change the API, the stability of that compound can no longer be assumed.4 Interactions between new or added ingredients within a formula can change the stability of a preparation and may warrant assigning a new BUD.4


Container Closure Systems


Selecting the right type of container is important to ensure the stability of a CNSP. Compounding personnel should check to see if the drug is compatible with the anticipated container. Not every drug will be stable in every type of container.6 In general, glass tends to be the most inert and stable container material. However, plastic is commonly used and presents concerns related to stability.6


Signs of Instability


It is important for compounding personnel to observe CNSPs periodically for signs of instability. Fortunately, pharmacists and pharmacy technicians are often able to recognize signs of instability for many different dosage forms visibly. Table 3 describes signs of instability.6


Table 3. Signs of CNSP Instability6

Dosage FormSigns of Instability

Hardening or softening of capsule shell

Discoloration or expansion of shell

Solutions, elixirs, syrupsCaking


Release of pressure on opening container

EmulsionsBreaking or creaming of emulsion

Inability to resuspend by shaking


Crystal growth


Emulsion breakage

Crystal growth



Change in consistency

Liquid separation



Excess softening


Changes in melting point



Assigning Beyond-use Dates to CNSPs


The ultimate responsibility for assigning beyond-use dates falls to compounding personnel, with oversight from the designated person or persons.1 The concept of a designated person is new within the revised guidelines. These individuals are deemed responsible by their institution and must use professional judgment when determining beyond-use dates.1 Ideally, each institution should utilize a standardized, guideline-driven approach and have established policies and procedures for assigning beyond- use dates. BUD recommendations within USP <795> assume the product is packaged in a light-resistant, tight container (unless other conditions apply).1

Beyond-use dating guidelines have undergone significant revisions since the 2014 publication. Prior to the released revisions, the two categories that distinguished BUD were called “nonaqueous” and “water-containing.”8 However, these terms were found to be confusing because it was unclear how to determine whether a substance or vehicle contained a small amount of water under certain scenarios.8 Table 4 provides the previous beyond-use dating guidelines for comparison.


Table 4. Previous Beyond-use Dating Guidelines9

Formulation TypeBeyond-use Date
Nonaqueous formulations6 months or the time remaining until the earliest expiration of any API
Water-containing oral formulationNot later than 14 days at controlled cold temperatures
Water-containing topical and dermal and mucosal liquid semisolid formulationsNot later than 30 days


Water Activity


Water makes up the greatest percent of any ingredient within compounded preparations and before discussing the new guidelines, an understanding of the terms water content and water activity and their relationship to CNSPs is needed. Water content is defined as the total amount of water present in a product, including bound and free water.10 Water activity (aw) is a measure of water available to react with or attach itself to other materials and is free water.10 Information on water activity is detailed in Chapter <1112> Application of water activity determination to nonsterile pharmaceutical products.11 The USP defines water activity as the ratio of vapor pressure of H2O in product (P) to vapor pressure of pure H2O (Po) at the same temperature.11 Numerically, it is equal to 1/100 of the relative humidity (RH) generated by the product in a closed system.11 RH can be calculated from direct measurements of partial vapor pressure or dew point or indirect

measurement by sensors whose physical or electric characteristics are altered by the RH to which they are exposed.11


The relationship between aW and equilibrium relative humidity (ERH) is represented by the following equations:


aW = P/Po and ERH(%) = aW × 10011


Water activity is a good indicator of microbial growth potential, and there are minimal levels of water required for the growth of mold, bacteria, and other organisms in a preparation.10 Table 5 lists the water activity levels for the growth of different organisms. In general, water activity levels under

0.60 will not support microbial proliferation.10 Substances with higher water activity levels will typically support more microorganisms.10 It is necessary to recognize that even though some nonsterile products such as ointments are not ingested orally, they can still support the growth of organisms that could harm patients.11 When water is present in a CNSP, compounding personnel can lower the aw by changing the concentration of ingredients such as sodium chloride to make it self-preserving, or add a preservative to protect against microbial growth and patient harm.10


Table 5. Water activity values10

OrganismMinimum Water Activity
Listeria monocytogenes0.92
Staphylococci and micrococci0.87


Looking at the big picture, it becomes clear why compounding personnel should take water activity into account when assigning a beyond-use date. In general, the lower the water activity level, the longer the BUD that may be assigned. Understanding and determining the water activity of nonsterile dosage forms is helpful for compounding personnel. This information can help with the following decision:11

Optimizing product formulations to improve antimicrobial effectiveness of preservative systems

Reducing the degradation of active pharmaceutical ingredients within product formulations susceptible to chemical hydrolysis,

Reducing the susceptibility of formulations (especially liquids, ointments, lotions, and creams) to microbial contamination, and

Providing a tool for the rationale for reducing the frequency of microbial limit testing and screening for objectionable microorganisms for product release and stability testing


For reference, Table 6 details the water activity of numerous dosage forms.1


Table 6. Water Activity of Common Compounded Nonsterile Dosage Forms1

Nonaqueous Dosage Forms: aw < 0.6Aqueous Dosage Forms: aw ≥ 0.6
Dosage FormDescriptionawDosage FormDescriptionaw


Animal treat


Animal treat (oil flavor)




Animal treat

Animal treat with 15%–

18% aqueous flavor




Capsule (oil filled)


Olive oil encapsulated





Cream vehicle (oil in water emulsion, petrolatum





Capsule (powder filled)


Powder base encapsulated





Emollient cream (petrolatum and mineral





Gel (glycol based)

Propylene glycol, ethoxy diglycol, hydroxypropyl

cellulose gel





Cream (oil in water emulsion with natural oils)



Nonaqueous Dosage Forms: aw < 0.6Aqueous Dosage Forms: aw ≥ 0.6
Dosage FormDescriptionawDosage FormDescriptionaw
Lollipop (sorbitol based)Sorbitol- based lollipop





Foaming surfactant solution



OintmentHydrophilic petrolatum0.396Gel (water based)Alcohol-free aqueous gel0.990



Polyethylene and mineral

oil gel base



Gel (water based)

Hydroxypropyl methylcellulose

(HPMC) gel




Oral solution (glycol based)


Polyethylene glycol and 80%

propylene glycol






Lotion (oil in water emulsion)



Oral solution (oil based)Medium chain triglycerides oil



Nasal spray


Nasal spray



Oral suspension (fixed oil)


Fixed oil with thickener



Oral solution

(water based)


Low-sucrose syrup vehicle




Powder for inhalation

Encapsulated powder for inhalation



Oral solution (water based)

90% Water

and 10% glycerin






Lip balm



Oral suspension (water


Oral suspension base





Polyethylene glycol base





Polymer gel with 30% water



SuppositoryFatty acid base0.385ShampooShampoo0.976
Tablet (compressed)Compressed tablet0.465Simple syrupSimple syrup0.831
Tablet (triturate)Tablet triturate0.427
Nonaqueous Dosage Forms: aw < 0.6Aqueous Dosage Forms: aw ≥ 0.6
Dosage FormDescriptionawDosage FormDescriptionaw
 (lactose and/or sucrose)    
Troche or lozenge (gelatin based)

Gelatin troche or lozenge with NMT 3% aqueous








Troche or lozenge (glycol based)

Polyethylene glycol troche or lozenge with NMT 3% aqueous









New Guidelines


Table 7 provides the most recent beyond-use dating recommendations from USP <795>, including the type of preparation, its associated BUD, and recommended storage temperature. In terms of temperature, controlled room temperature (CRT) is defined as 25⁰C, and refrigerated temperature is between 2⁰C and 8⁰C.1


When preparing CNSPs, personnel should note that materials and equipment contribute to the microbial growth risk of the final preparation.1 Per USP 795, CNSPs with an aw ≥ 0.6 and a BUD within the limits of Table 7 should contain appropriate antimicrobial agents to protect against the growth of bacteria, yeast, and mold that may be inadvertently introduced anytime during the compounding process or throughout the BUD under appropriate handling and storage conditions.1 In choosing a preservative, consideration should be given as to its effectiveness in preventing microbial growth and maintaining the stability of the preparation.1 When antimicrobial preservatives are contraindicated in a CNSP, storage of the preparation in a refrigerator is

required if such storage does not change the physical or chemical properties of the CNSP (i.e., precipitation).1


Table 7. New BUD Recommendations1

Type of preparationBUDStorage Temp
Aqueous dosage forms with water activity ≥ 0.60
Non-preserved aqueous dosage form14Refrigerator
Preserved aqueous dosage form35CRT or refrigerator
Nonaqueous dosage forms with water activity <0.60
Oral liquids (nonaqueous)90CRT or refrigerator
Other nonaqueous dosage forms180CRT or refrigerator


CNSPs that Require Shorter BUD


The beyond-use dating requirements in USP 795 provide recommendations without considering the potential impact of stability.1 However, the designated person is still responsible for determining if relevant stability data exists that may require a shorter beyond-use date.1 Per USP 795, the BUD of the CNSP must not exceed the shortest remaining expiration date of any of the commercially available starting components. This includes both the active ingredients and any excipients used.1 For example, if a product would normally be assigned a beyond-use date of 180 days per the guidelines but an API is used that expires within the next two months, a BUD of two months would be assigned to the preparation instead. Similarly, CNSPs that are prepared from one or more compounded components should be assigned BUDs that do not exceed the shortest BUD of any individual compounded component.1


There may be instances in which it is acceptable to assign a BUD to the final CNSP that exceeds the BUD assigned to compounded components (for example, pH-altering solutions).1 If the assigned BUD of the final CNSP

exceeds the BUD of the compounded components, the physical, chemical, and microbiological quality of the final CNSP must not be negatively impacted.2 The designated person should ensure this is done appropriately and according to institutional standard operating procedures (SOP).1


CNSPs with Extended BUDs


Compounding personnel may wish to extend the BUD of a CNSP, and there are certain cases in which this is permissible. Before doing so, compounders need to thoroughly understand the formulation and evaluate pertinent data using professional judgment.4 In general, a BUD cannot be extended when a USP-NF monograph is used to compound the preparation.1 If compounding personnel wish to extend the BUD, they must have appropriate stability studies using stability-indicating analytical methods for the API, CNSP formulation, and material composition of the container-closure system.1,4 A stability-indicating method is defined as a validated analytical procedure that accurately and precisely measures the active ingredients free from process impurities, excipients, and degradation products, and it must be validated for specific formulation testing.12 The BUD could then be extended beyond USP recommendations, up to a maximum of 180 days.1


By performing a stability study, compounding personnel can benefit from the reduced waste of the drug and increased efficiency.12 Stability studies should be conducted via a verified third-party testing lab, which can be costly for facilities. Data could also be obtained from published literature, ensuring all study information matches the intended CNSP, including its container and storage conditions.4 When completing stability-indicating assays, there are many important points to keep in mind. First, compounding personnel should recognize the stability of a product in studies may be formulation-specific, and thus if they elect to change an ingredient, a new stability study should be completed.12 Even changing one excipient could result in a large change in stability.4 With regard to degradation limits, the assay of the product should remain within 90% to 110% of the label claim at a minimum.12 Personnel can determine result trends by testing at least three lots at many different time points.12

If a decision is made to extend the BUD, the product must be tested for antimicrobial effectiveness.1 Information regarding this testing can be found in Chapter 51 – Antimicrobial Effectiveness Testing within USP.13 Within this chapter, it is noted antimicrobial preservatives should not be used as a way to substitute for good manufacturing practices or to reduce the viable microbial population of a nonsterile product solely.13 If there is available peer- reviewed literature that matches the CNSP formulation and container closure system, that data could be used in lieu of testing. Designated persons could also opt to rely on tests from an FDA-registered facility.1 Choosing to extend a BUD requires strict documentation, and all relevant information, including supporting references, should be included on an institution’s MFR for the product in accordance with the SOP.1


Beyond-use Date Labeling and Documentation




Compounded nonsterile preparation labeling must comply with laws and regulations pertinent to the applicable regulatory jurisdiction. Per USP, the term “label” designates the part of the labeling that is on the immediate container.1 The BUD is considered a minimum requirement of the CNSP label and should be displayed both prominently and legibly.1 Beyond-use dates should be listed on CNSP labels as the date or hour and date beyond which the product should not be used.1 Related storage conditions should also be listed, except for products stored at controlled room temperature.1 BUDs can be noted on labels using the following phrases:


“Do not use after:     ”

“Discard after:      ”

“Use before:      ”




The process of preparing CNSPs requires stringent documentation, including the completion of the compounding record.1 United States

Pharmacopeia <795> guidelines state that such a record must be created for all CNSPs. This documentation must comply with relevant laws and regulations within applicable regulatory jurisdictions, and the required CR must be retrievable for at least 2 years (or as required by regulatory jurisdiction laws). The beyond-use date (with related storage requirements) is a requirement of compounding records.1


Further, designated persons should ensure a standardized format for formulations. Beyond-use dates should be included with appropriate references.1 As an example, in one study, a health system created a standardized formulation record system, developed a computerized system so all pharmacists could access these records, and improved the quality control process for extemporaneously compounded nonsterile formulations.14


CNSP Beyond-use Dates: Dos and Don'ts




Assign the more conservative date when there is conflicting information between regulatory agencies

Maintain written policies and procedures to ensure standard BUD assignment for each CNSP

Keep patient safety at the forefront of BUD assignment




Establish a BUD without considering stability implications

Exceed the manufacturer expiration date of any ingredient in the CNSP

Trade patient safety for convenience


Beyond-Use Dating Resources


Pharmacists and pharmacy technicians looking for additional resources related to beyond-use dating have several good options.6 These include the following:

Trissel’s Stability of Compounded Formulations

AHFS Drug Information monographs

International Journal of Pharmaceutical Compounding

American Journal of Health-System Pharmacy

Hospital Pharmacy

Other primary literature




Compounding personnel should recognize the importance of and be knowledgeable regarding the assignment of appropriate beyond-use dates to compounded nonsterile preparations. Numerous factors must be considered when assigning a beyond-use date, with the stability of the preparation requiring specific consideration. A variety of factors have the potential to impact the stability of CNSPs, and compounding personnel should understand these factors and their ramifications. Pharmacists and pharmacy technicians should adhere to USP, Chapter <795> guidelines, including recommendations for extending beyond-use dates. All compounding personnel should refer to their state boards of pharmacy for guidance regarding beyond-use dating.

Course Test


Which of the following is true regarding factors that may impact the stability of a compounded nonsterile preparation (CNSP)?


For every 10-degree increase in temperature, the rate of drug degradation will decrease exponentially

To minimize the risk of oxidation, container headspace should be increased as much as possible

Oxidation can be prevented by decreasing the amount of air entrapped within a preparation

Moisture and humidity can lead to oxidative reactions


True or False: Changing an excipient within a formulation will not impact its stability.





Which of the following is true regarding water activity?


Water activity is defined as the total amount of water present in a product

Water activity includes free and bound water

Water activity is a good indicator of microbial growth potential

Water activity values under 0.80 will not support microbial growth


Which of the following dosage forms has a water activity value of






Gel (water based)


Which of the following water activity values would be unlikely to support microbial growth?






Per USP <795>, which of the following beyond-use dates would be assigned to a non-preserved aqueous dosage form with water activity ≥0.60 stored in the refrigerator?


14 days

35 days

90 days

180 days


Per USP <795>, which of the following beyond-use dates would be assigned to a preserved aqueous dosage form with water activity ≥0.60 stored at controlled room temperature?


14 days

35 days

90 days

180 days


Per USP <795>, which of the following beyond-use dates would be assigned to a nonaqueous dosage form with water activity

<0.60 stored in the refrigerator?


14 days

35 days

90 days

180 days


What is the maximum beyond-use date a CNSP can be assigned?


180 days

240 days

360 days

There is no limit


Which USP Chapter contains information on antimicrobial effectiveness testing?


Chapter 15

Chapter 51

Chapter 1121

Chapter 1190



General Chapter: USP. Pharmaceutical Compounding-Nonsterile Preparations <795>. In: USP-NF. Rockville, MD: USP; September 2022.

General Chapter: USP. Labeling<7>. In: USP-NF. Rockville, MD: USP; May 2020.

Pitt R, et al. The Pharmacist Guide to Assigning a Beyond-use Date to a Compounded Sterile or Nonsterile Preparation. ASHP (American Society of Health System Pharmacists).

/media/assets/pharmacy-practice/resource- centers/compounding/docs/The-Pharmacist-Guide-to-Assigning-a- Beyond-Use-Date-_final.pdf. Accessed September 30, 2022.

Thomson CM, Savji T. Standards of practice, professional judgment, and scientific evidence to establish and extend a beyond-use date. Int J Pharm Compd. 2014;18(6):456-460.

Open Forum - Beyond Use Date (BUD) Provisions in General Chapters

<795> & <797 >. USP. 2020. involved/stakeholder-forums/hqs/bud-provisions-gc. Accessed September 30, 2022.

Lloyd A. The art, science, and technology of pharmaceutical compounding. 6th edition. American Pharmacists Association. 2020.

General Chapter: USP. Stability Considerations in Dispensing Practice

<1191>. In: USP-NF. Rockville, MD: USP; May 2018.

USP <795> and <797> Beyond-use date updates. US Pharmacist. November 18, 2022.

beyonduse-date-updates. Accessed September 30, 2022.

General Chapter: USP. Pharmaceutical Compounding-Nonsterile Preparations <795>. In: USP-NF. Rockville, MD: USP; September 2020.

Allen LV Jr. Quality Control: Water Activity Considerations for Beyond- use Dates. Int J Pharm Compd. 2018;22(4):288-293.

General Chapter: USP. Application of water activity determination to nonsterile pharmaceutical products <1112>. In: USP-NF. Rockville, MD: USP; 2013.

Extended beyond-use dating for compounded preparations presentation webinar Q & A. ARL Bio Pharma. e%20Dating%20Q%26A_1.pdf. Accessed September 30, 2022.

General Chapter: USP. Antimicrobial effectiveness testing <51>. In: USP-NF. Rockville, MD: USP; September 2022.

Evans A, Haile M, Anderson K. Development of a standardized intranet database for formulation records of nonsterile compounding, part 1. IJPC. 2010;14(5).



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