Compounding nonsterile preparations:

USP <795> and <800>

Patricia C. Kienle, RPh, MPA, FASHP,

Abstract Director, Accreditation and Medication Safety,
Cardinal Health Innovative Delivery Solutions,
Objective: To identify the key components of USP <795> Pharmaceutical Com- Wilkes Barre, PA
pounding—Nonsterile Preparations and USP <800> Hazardous Drugs—Handling in
Healthcare Settings that are required and recommended when compounding non- Correspondence: Patricia C. Kienle, Cardinal
sterile preparations, and to prioritize elements that need to be improved to come Health Innovative Delivery Solutions, 106
into compliance. Elmwood Dr., Wilkes Barre, PA 18702-7226;
Summary: USP General Chapters numbered under <1000> are enforceable by Patricia.Kienle@cardinalhealth.com
regulators and accreditation organizations. These include USP <795> Pharmaceuti-
cal Compounding—Nonsterile Preparations and USP <800> Hazardous Drugs—Han-
dling in Healthcare Settings. Many state boards of pharmacy include them in regu-
lations. Pharmacists and pharmacy technicians who compound must be aware
of and comply with the USP chapters and related best practices. Compounding
hazardous drugs includes requirements in addition to those in <795>. This article
identifies the requirements compounders must use to comply with best practices
and protect patients from harm.
Conclusion: Pharmacists and pharmacy technicians who compound nonster-
ile preparations need to be aware of the requirements and recommendations of
the applicable USP chapters and of best practices promulgated by professional or-
ganizations. USP <795> details requirements for nonsterile compounding activi-
ties; USP <800> details additional requirements when handling hazardous drugs.
Even if facility changes are not required to come into compliance with USP <800>
by July 1, 2018, every pharmacy will need to complete an Assessment of Risk to
define how hazardous drugs will be safely handled.
Pharm Today. 2017;23(10):56–72

Accreditation Information Learning objectives

Provider: APhA Expiration date: October 1, 2020 Upon completion of this activity, pharma-
Activity type: Knowledge-based ACPE Universal Activity Number: cists and pharmacy technicians will be
Learning level: 1 0202-0000-17-232-H07-P/T able to
Target audience: Pharmacists and pharmacy CPE credit: 2 hours (0.2 CEUs) ■■ Describe how USP standards become
technicians Fee: There is no fee associated with this activ- part of regulatory requirements,
Release date: October 1, 2017 ity for APhA members. There is a $25 fee for accreditation standards, and best
nonmembers. practice recommendations.
The American Pharmacists Association (APhA) is accredited by the Accreditation Council ■■ Differentiate elements of nonsterile
for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). compounding, including categories,
The ACPE Universal Activity Number assigned to this activity by the accredited provider is types of components, expiration vs.
0202-0000-17-232-H07-P/T. beyond-use dates, and documentation.
Advisory board: Ryan A. Forrey, PharmD, MS, FASHP, Senior Manager, Hazardous Drug Safety, ■■ State the scope and controls designed
Becton Dickinson, Franklin Lakes, NJ. to protect health care personnel from
Disclosures: Patricia C. Kienle, RPh, MPA, FASHP, declares that she is employed by Cardinal contamination with hazardous drugs.
Health. Ryan A. Forrey, PharmD, MS, FASHP, declares that he is employed by Becton Dickinson (BD). ■■ Cite the document that lists drugs
APhA’s editorial staff declare no conflicts of interest or financial interests in any product or service that are hazardous to health care
mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For personnel.
complete staff disclosures, please see www.pharmacist.com/apha-disclosures. ■■ Identify the types of hazardous drugs
Development: This home-study CPE activity was developed by APhA. and dosage forms that may be consid-
ered for an Assessment of Risk and
the related contamination controls and
work practices.

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 COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800> CPE

sary. When new chapters or revisions to current chap-

Preassessment questions
Before participating in this activity, test your knowledge by
ters are proposed, they are published in Pharmacopeial
answering the following questions. These questions will also be Forum and are available for public comment.8
part of the CPE assessment. ■■ Monographs include two types of documents:
–Documents for bulk drug substances, such as Cloni-
1. What is the role of USP?
a. Enforce state regulations. dine, USP,9 provide standards for the identity, quality,
b. Enforce federal regulations. purity, strength, packaging, and labeling of compo-
c. Set standards. nents used in compounds
d. Define accreditation standards. –Documents for specific preparations, such as Alprazol-
am Compounded Oral Suspension, USP,10 provide detailed
2. USP General Chapters are information for compounding preparations that are
a. Standards
b. Guidelines
not available during shortages or from FDA-registered
c. Stretch goals manufacturers
d. Outcomes USP standards are developed through a standardized
process (Figure 1). Once a public health need is identified,
3. USP General Chapters numbered under <1000> are draft standards are developed by a USP Expert Committee
a. Advisory and published for public comments. After a public com-
b. Enforceable
ment period, the Expert Committee reviews and revises
c. Informational
d. Guidelines the draft document based on the comments received. Once
approved, the standard is published as an official docu-
ment in the USP–National Formulary (NF).
Chapter numbering in USP is significant. Chapters num-
bered under <1000> are enforceable; those numbered over
Introduction <1000> are informational. Over time, some informational
Compounding is a core competency of pharmacy practice. chapters are revised and changed to enforceable chapters.
Federal and state regulations identify the specific require- The concepts in General Chapter <795> began with USP
ments of pharmacists and others legally allowed to com- <1161> Pharmacy Compounding Practices when the 1997 Food
pound in those jurisdictions. and Drug Administration Modernization Act became law.
Since 1820, USP has provided guidance for standard- USP <1161> was retired when <795> was published in
izing drug compounding and manufacturing. USP Chap- USP 24–NF 19 in 2000. USP <795> was revised in 2004 and
ters <795> Pharmaceutical Compounding—Nonsterile Prepara- again in 2011, when <1075> Good Compounding Practices was
tions1 and <800> Hazardous Drugs—Handling in Healthcare incorporated. A Revision Bulletin posted on November 22,
Settings2 include contemporary requirements and recom- 2013, clarified the distinction between <795> and <797>
mendations related to compounding nonsterile prepara- and became official on January 1, 2014.11
tions. Though USP is not a government entity, it works Any pharmacist who compounds needs to have access to
with regulatory agencies to provide standards of identity, the USP standards. The USP Compounding Compendium
strength, quality, and purity. USP standards are specified is available for purchase as an electronic publication.12
in the Federal Food, Drug, and Cosmetic Act, 3,4 in many
state regulations, and in standards promulgated by ac- Renewed emphasis on compounding safety
creditation organizations, such as The Joint Commission The national outbreak of fungal meningitis caused by com-
(TJC)5 and the Pharmacy Compounding Accreditation pounds distributed by the New England Compounding
Board (PCAB), a division of the Accreditation Commission Company that were intended to be sterile13,14 resulted in
for Health Care.6 increased emphasis on the safety of both nonsterile and ster-
ile compounding. A total of 64 patients died, and more than
USP standards 753 were affected by fungal meningitis. The public furor over
USP standards include three major categories: this egregious situation resulted in the 2013 Drug Quality
■■ General Notices provide the basic definitions for ap- and Security Act (DQSA).15
plying USP standards. The information in the General The DQSA created a separation in Section 503 of the Fed-
Notices applies to any of the more descriptive general eral Food, Drug, and Cosmetic Act, resulting in two parts:
chapters and monographs, such as <659> Packaging and 503A, pertaining to compounding pharmacies; and 503B,
Storage Requirements.7 pertaining to a new entity, registered outsourcing facilities.
■■ General Chapters contain more detailed information Though generally focused on sterile preparations, the con-
about a function, such as nonsterile compounding in cepts in this legislation influence all compounding activities.
<795> and hazardous drugs (HDs) in <800>. General In June 2017, the FDA commissioner issued a statement
Chapters numbered under <1000> are minimum re- indicating the importance of DQSA in overseeing com-
quirements, not guidelines or goals. All elements of the pounded drugs16 and a Human Drug Compounding Prog-
chapter need to be used; partial compliance is not ac- ress Report (see “Highlights of FDA’s Human Drug Com-
ceptable. USP General Chapters are updated as neces- pounding Progress Report” sidebar).17
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 CPE COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800>

Figure 1. Development of USP standards

Source: Used with permission. USP, ©2016.

Highlights of FDA’s Human Drug Compounding other organizations’ regulations and guidance documents
Progress Report may limit the ability to compound such mixtures under any
■■ Explain risks of compounded drugs. circumstances.
■■ Differentiate between 503A compounding pharmacies and
503B outsourcing facilities.
■■ Explain FDA oversight of compounding.
Regulations
■■ Describe policy development and stakeholder collaboration. Federal and state agencies issue regulations and require com-
■■ Define the function of PCAB. pliance. USP standards are incorporated in many regulations,
sometimes by reference to the USP–NF, sometimes by citing
As a result of this increased emphasis on compounding specific chapters or general notices, and sometimes by plac-
safety, USP, FDA, states, and accreditation organizations (e.g., ing text from the USP standards into federal or state regula-
PCAB) now require pharmacists and pharmacy technicians tions. The Occupational Safety and Health Administration’s
who compound to comply with current best practices pro- (OSHA) 1970 Occupational Safety Act General Duty Clause
mulgated in regulations and guidance documents. requires employers to provide a workplace “free from recog-
Drug shortages and prescriber and patient requests for nized hazards that are causing or are likely to cause death or
compounds may create an ethical burden to determine if serious physical harm.”18 This issue is significant for phar-
compounding is appropriate. In particular, drugs that are macy personnel who handle HDs and other hazards in the
difficult to compound, copies of commercially available workplace. (See Table 1.)
products, drugs withdrawn from the U.S. market for safety For those who work in hospitals and health systems,
reasons, and use of manufacturing-scale equipment should CMS requires compliance with Conditions of Participation
be avoided unless extenuating circumstances exist. FDA and (in hospitals and critical access hospitals) or Conditions for

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 COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800> CPE

Table 1. Legal considerations and compliance impact

Legal considerations Compliance impact

1997 FDA Modernization Act requires compliance with USP USP <795> and <797> are existing enforceable standards; <800>
monographs. becomes enforceable on July 1, 2018.
2013 Drug Quality and Security Act reaffirmed USP, specifically Compounding requirements are included in the CMS Conditions of
referencing USP <795> and <797>. Participation.
Accreditation organizations include compounding issues in their
USP standards are included in many state laws and regulations. standards.
Source: Adapted from USP <795>.

Coverage (for many other types of health care entities).19 need to comply with USP <795> and the other USP General
USP <795>, <797>, and other references to compounding Chapter references in <795>:
are listed in §482.25© and §485.25 of the Hospital Conditions ■■ <659> Packaging and Storage Requirements
of Participation.20 ■■ <1136> Packaging and Repackaging Single-Use Containers
FDA has produced a number of final and draft guidance ■■ <1151> Pharmaceutical Dosage Forms
documents and other documents on compounding (see Ta- ■■ <1160> Pharmaceutical Calculations in Pharmacy Practice
ble 2 for examples of selected documents related to nonster- ■■ <1163> Quality Assurance in Pharmaceutical Compounding
ile compounding).21 ■■ <1176> Prescription Balances and Volumetric Apparatus Used
in Compounding
State regulations ■■ <1191> Stability Considerations in Dispensing Practice
Compounding regulations vary among states but generally ■■ <1231> Water for Pharmaceutical Purposes
restrict oversight of compounding to a pharmacist. Often, ■■ <1265> Written Prescription Drug Information
technicians are able to compound under the direction of a
pharmacist. Practitioners must be aware of and comply with USP <795> Pharmaceutical Compounding—
the regulations of the state in which compounding occurs. Nonsterile Preparations
If they are providing patient-specific compounds to another General Chapter USP <795> presents the standards of care
state, they must comply with regulations of that state.22 required when nonsterile preparations are compounded.
Major elements include
Accreditation organizations ■■ Categories of compounds
Accreditation organizations are not regulators, but often ■■ Personnel requirements
their standards are used in lieu of or to supplement regula- ■■ Facility requirements
tory inspections. Their standards include medication-related ■■ Component selection
requirements, and many have recently increased their focus ■■ Beyond-use dates
on compounding. For example, PCAB offers a compound- ■■ Documentation requirements
ing pharmacy accreditation, and TJC offers a certification in
medication compounding. Categories of nonsterile compounds
USP <795> defines three categories of nonsterile compounding:
Best practices simple, moderate, and complex. The distinctions are based on
Professional organizations, including APhA, the American the degree of difficulty and the availability of scientifically
Society of Health-System Pharmacists (ASHP), the American valid information about the stability of the compound.
College of Apothecaries, the International Academy of Simple compounds include those for which clear data are
Compounding Pharmacists, and others, provide guidance available, such as information from a manufacturer in the
documents on compounding. FDA-approved labeling or information detailed in most of
the USP compounding monographs.
Compounding nonsterile preparations For example, the supplier of an 80-mL bottle of amoxicil-
Compounding performed in most pharmacies is limited to lin oral suspension, USP, instructs compounders to add 59
preparations for human use and may include ingredients con- mL of water to the bottle to create a final concentration of
sidered hazardous by the National Institute of Occupational 250 mg/5 mL. Further information provided may include in-
Safety and Health (NIOSH). NIOSH-hazardous medications structions such as
include antineoplastics, hormones, and a number of other ■■ Shake well before using.
commonly compounded medications. Some pharmacies also ■■ Keep bottle tightly closed.
compound medications for animal patients, which requires ■■ Discard unused portions after 14 days.
specialized knowledge of the type of animal (companion, ■■ Refrigeration is preferable but not required.
food, or performance) and species-related aspects. Nuclear Those specific details have been researched by the manufac-
pharmacies may compound oral radiopharmaceuticals. All turer and are included in the FDA-approved product labeling.
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 CPE COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800>

Table 2. Selected documents related to nonsterile compounding

Final guidance documents
Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Issued 10/26/2015
Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Issued 6/9/2016
Cosmetic Act: Guidance for Industry Revised 1/13/17
Additions and Modifications to the List of Drug Products That Have Been Withdrawn or Removed From the Market
for Reasons of Safety or Effectiveness Issued 10/6/2016
Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act Issued 12/28/2016
Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities Issued 1/12/2017
Draft guidance documents
Hospital and Health System Compounding Under the Federal Food, Drug, and Cosmetic Act Issued 4/15/2016
Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section
503A of the Federal Food, Drug, and Cosmetic Act: Guidance for Industry Issued 7/7/2016
Insanitary Conditions at Compounding Facilities: Guidance for Industry Issued 8/3/2016

Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies and Federal

Facilities Guidance for Industry Issued 12/28/2016
Revised Draft Guidance: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved
Biologics License Application Issued 1/12/2017
Other documents
Draft Memorandum of Understanding Addressing Certain Distributions of Compounded Human Drug Products
Between the State of [insert STATE] and the U.S. Food and Drug Administration Issued 2/13/2015
Request for Nominations: Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance
With Section 503A of the Federal Food, Drug, and Cosmetic Act Issued 10/26/2015
Proposed Rule: Amendments to the Regulation Regarding the List of Drug Products That Have Been Withdrawn or
Removed from the Market for Reasons of Safety or Effectiveness Issued 10/18/2016
Proposed Rule: List of Bulk Drug Substances That Can Be Used to Compound Drug Products Issued 12/15/2016

Two situations present when using an Active Pharma- ration for which no stability data are available for that par-
ceutical Ingredient (API) in simple compounding: when us- ticular formulation, or mixing a preparation that requires
ing USP monographs and when using commercially avail- specialized calculations or procedures that exceed what
able kits containing APIs. USP <795> defines API as “any would be considered simple compounding. A common ex-
substance or mixture of substances intended to be used in ample of moderate compounding is mixture of two topical
the compounding of a drug preparation, thereby becom- ingredients when the stability of the mixture is not known.
ing the active ingredient in that preparation and furnishing Some USP monographs, such as Morphine Sulfate Compounded
pharmacological activity or other direct effect in the diagno- Suppositories, are considered moderate compounding.
sis, cure, mitigation, treatment, or prevention of disease in Complex compounding includes creating a preparation
humans and animals or affecting the structure and function that requires special training, facilities, equipment, or pro-
of the body.”1 cedures. Examples of complex compounding include mak-
Several companies supply kits including APIs and other ing transdermal dosage forms or modified-release prepara-
components and supplies needed to provide a patient-spe- tions. Compounders must be aware of the FDA documents
cific compound. Mixing of these kits according to instruc- on preparations considered “demonstrably difficult” to com-
tions backed by valid studies is an example of simple com- pound and should follow the outcomes of FDA’s Pharmacy
pounding. Compounding Advisory Committee.24
Most USP monographs also are considered simple com-
pounding because the procedures are straightforward and Requirements, recommendations,
scientifically valid details have been evaluated. USP 40 con- and best practices
tains almost 200 compounding monographs.23 The mono- USP General Chapters have a specific wording convention:
graphs include information on formulas, instructions for “shall” or “must” means that the statement is a requirement;
compounding, beyond-use dates ([BUDs] which often exceed “should” means that the statement is a strong recommenda-
the default dates that would need to be used without this in- tion. Some states or accreditation organizations also require
formation), packaging and storage information, and other compliance with should statements, so knowledge of the
details. They are designed for compounding patient-specific jurisdiction’s or accreditation organization’s standards is key.
preparations when no suitable conventionally manufactured A summary of shall statements follows each section in this
product is available. CPE article. The term “should” used in this text does not nec-
Moderate compounding includes either mixing a prepa- essarily mean that similar wording appears in <795>.

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 COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800> CPE

Personnel requirements pounding needs. Resources can be developed or purchased

Any person who compounds nonsterile preparations needs to target needs of each compounder, but all individuals in the
to be competent to do so and should demonstrate proficiency pharmacy need to demonstrate compliance with the require-
to a skilled compounder. ments, even those who have compounded at other organiza-
To standardize procedures among all who compound, tions and those who may not compound but are responsible
the pharmacy needs to establish and regularly review poli- for checking preparations.25,26
cies and procedures to guide safe compounding (see “Ex- On an annual basis, the designated person should assess
ample list of policies and procedures” sidebar). The list is not the skills of all who compound and document the observa-
exhaustive, and each pharmacy needs to ensure that all key tions in the compounder’s personnel record. Any needed
functions are described in their documents. remediation also needs to be documented. Resources can
be developed or purchased that provide standardized ele-
Example list of policies and procedures ments that each compounder should demonstrate.27
■■ Scope of compounding As new compounds, equipment, procedures, or other
■■ State board of pharmacy regulations changes that could affect compounding are incorporated, the
■■ Training of personnel designated person or a designee needs to provide in-service
■■ Acknowledgment of handling of HDs
training to staff and ensure competency is documented. New
■■ Compounding supervisor
■■ Responsibilities of compounding personnel equipment should only be used once it has been checked to
■■ Facilities ensure it is operating as intended, personnel are trained, and
■■ Equipment personnel competency is documented.
■■ Supplies Work practices such as hand hygiene, proper garbing,
■■ Storage parameters meticulous technique, and the ability to perform the required
■■ Master Formulation Records procedures are essential to monitor. To protect the processes
■■ Compounding Records
established and to keep patients safe, compounding person-
■■ Equipment initial and preventive maintenance
■■ Daily documentation requirements nel should also identify situations that need to be brought to
■■ Cleaning the pharmacist in charge or designated person.
■■ Recalls Compounding HDs requires additional training and
■■ Patient complaint procedures monitoring. See the section on Hazardous Drugs for addi-
tional requirements when handling HDs.
A person who oversees compounding activities should
be assigned. In <800>, this individual is called a “designated Shall statements in <795> concerning personnel
person.” The designated person needs to be highly skilled The compounding supervisor shall
in compounding, have the ability to oversee personnel ac- ■■ Meet with employees to review their work, and answer any
tivities, and understand the complexity of the compounding questions the employees may have concerning compounding
procedures.
performed at the pharmacy. The individual does not neces-
■■ Demonstrate the procedures for the employee.
sarily need to be a pharmacist (unless required by the state ■■ Observe and guide the employee throughout the training
or accreditation organization) or in a supervisory-level posi- process.
tion. The individual may have responsibilities for more than ■■ Be physically present and approve all ingredients and their
one site if permitted in the organization’s policy. The scope quantities and the final preparation.
of compounding will dictate the appropriate qualifications ■■ Constantly monitor the work of the employee, and ensure
of the individual, but external training by experts should be that the employee’s calculations and work are accurate and
adequately performed.
considered for pharmacies that provide extensive or complex
compounding services. (See “Shall statements in <795> con- All compounders shall
cerning personnel” sidebar.) Day-to-day oversight is often ■■ Acquire and maintain knowledge and skills for which they
delegated to other qualified staff. compound.
Pharmacists and pharmacy technicians who compound ■■ Adhere to the general principles listed in <795>.
must ensure that the preparations they mix ■■ Be proficient and continually expand compounding knowl-
edge.
■■ Are appropriate for the patient
■■ Be properly trained.
■■ Have the acceptable strength, quality, and purity ■■ Document all training activities.
■■ Are prepared in accordance with the prescription or ■■ Read and become familiar with <795>, associated chap-
medication order ters and all applicable laws, regulations, guidelines, and
■■ Comply with requirements or restrictions in federal or standards.
state laws or regulations ■■ Read and become familiar with each of the procedures
■■ Follow the Master Formulation Record for those com- related to compounding.
Source: Adapted from USP <795>.
pounds that require it
■■ Are packaged and labeled to conform with policies and
safe practices Facility requirements
The designated person should develop a training pro- The current USP <795> does not provide much direction in
gram for employees new to that particular pharmacy’s com- the requirements for facilities (see “Shall statements <795>
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 CPE COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800>

concerning facilities” sidebar). State regulations may provide

Shall statements in <795> concerning component
more detail and often are specific as to location and square
selection
footage required for compounding functions. USP <795> ■■ Attempt to use components manufactured in FDA-registered
describes minimum requirements, including facilities.
■■ Adequate space specifically designated for compounding ■■ Use professional judgement in selecting an acceptable and
■■ Clean, orderly, sanitary, and in good state of repair reliable source when components cannot be obtained from
■■ Orderly placement of equipment and materials an FDA-registered facility, and establish purity and safety by
■■ Designed, arranged, and used to prevent cross-contam- reasonable means.
■■ Use purified water for compounding nonsterile preparations
ination
when water is included in the formulation.
■■ Well lighted ■■ Store components off the floor to prevent contamination and
■■ Appropriate heating, ventilating, and air conditioning permit inspection and cleaning.
■■ Hand- and equipment-washing facilities Source: Adapted from USP <795>.
■■ Plumbing system free of defects
USP <800> Hazardous Drugs—Handling in Healthcare Set-
tings provides details about the separate storage and com- If components must be obtained from a source that is
pounding facility requirements when handling HDs. HDs not FDA registered, the compounder must use professional
are not limited to those used for oncology; they include hor- judgment to ensure the component is appropriate and must
mones and some antibiotics, antipsychotics, diuretics, anti- obtain a Certificate of Analysis. Caution must be paramount
coagulants, and a variety of other common medications. See when using components that are not of compendial quality.
the Hazardous Drugs section in this article for more infor- Even though substances may be pure (such as those meet-
mation. ing American Chemical Society requirements), they may
present safety concerns because the chemicals have not been
Shall statements in <795> concerning facilities tested for use in patients. Additional caution must be used
■■ Design adequate space that is specific for compounding with components derived from ruminant animals (including
of prescriptions that is separate and distinct from sterile cattle, goats, and sheep). The supplier must provide written
compounding areas. assurance that the component complies with federal laws
■■ Place equipment and materials in an orderly manner.
governing processing, use, and importation.
■■ Maintain the compounding area in clean, orderly, and sani-
tary conditions and in a good state of repair. Dietary and nutritional supplements used in compounds
■■ Ensure that plumbing system is free from defects. must comply with any applicable federal and state regula-
■■ Provide potable water for hand and equipment washing. tions. Even though supplements are not drugs, they are eval-
■■ Provide adequate hand and equipment washing facilities uated for inclusion in FDA’s bulk component list. As this is
accessible to the compounding area that include (but are not an evolving list and regulation, be sure to stay current with
limited to) hot and cold running water, soap or detergent, and related information.
an air dryer or single-use towels.
A Certificate of Analysis must be issued for each batch
■■ Control heating, ventilation, and air conditioning systems to
avoid decomposition and containment of chemicals. of a component. The certificate should list the component,
■■ Hold and dispose of waste in a sanitary and timely manner in batch number, date testing was performed, and how each
accordance with federal, state, and local guidelines. test complies with the compendial requirement (if available),
Source: Adapted from USP <795>. and it should be dated and signed by an authorized individ-
ual from the manufacturer. When a firm different from the
Component selection manufacturer completes the testing or repackages the com-
Three types of components are described in <795>: API, ponent, both the manufacturer and the repackager informa-
added substances, and vehicles (see “Shall statements in tion should be listed on the Certificate of Analysis.28
<795> concerning component selection” sidebar). API is the When a conventionally manufactured FDA-approved
active ingredient that provides the pharmacological activity. drug product is used as a component in a compound, the
Added substances include inactive ingredients, excipients, compounder must evaluate all the components in the prod-
and other additives used to complete the compound. The uct, as they could affect the therapeutic appropriateness and/
vehicle is the carrier or diluent in which the API and added or stability of the final compounded preparation.
substances are dissolved or suspended. Expiration dates listed on APIs, added substances, and
The best option for obtaining ingredients is to select vehicles can be used through the date listed, provided care
those that are manufactured in an FDA-registered facility is taken to avoid decomposition. If the component is trans-
and have the USP, NF, or Food Chemicals Codex (FCC) des- ferred to a different container, the expiration date can still be
ignation. This provides the assurance that the components used as long as the container and closure’s integrity is at least
have been manufactured under the conditions described as good as that of the original container.
in the USP–NF compendium. Unless otherwise required, if If the component does not have an expiration date, the
USP, NF, or FCC components are used, the compounder does compounder must label the container with the date of receipt
not need to obtain a Certificate of Analysis, as the compen- and assign a conservative expiry date that is no longer than 3
dial requirements have been met and documented by the years from the date of receipt of the component.
manufacturing firm. Water used in nonsterile compounding must meet the

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standard of Purified Water, USP. Generally, this is water that

Shall statements in <795> concerning compounding
complies with U.S. Environmental Protection Agency Na-
practices
tional Primary Drinking Water regulations and contains no ■■ Store components and finished preparations off the floor and
other substances.28 Various methods of purification are ac- as directed by the manufacturer or according to USP, NF, or
ceptable, including the most common method of distillation. FCC monographs, including for appropriate temperature and
Equipment and supplies may be washed with potable water, humidity.
but consider rinsing them with purified water. ■■ Label preparations appropriately.
Storage of components must meet the requirements of the ■■ Handle and store components and finished preparations to
prevent contamination.
manufacturer and any compendial requirements of USP, NF,
■■ Rotate stock so that the oldest is used first.
or FCC, including temperature and humidity. If controlled ■■ Store components and finished preparations to permit in-
room temperature is required or recommended, the compo- spection and cleaning of the compounding and storage area.
nents can be stored between 20° and 25° C (68° to 77° F) with ■■ If a component will be transferred from the original con-
excursions allowed as detailed in <659>.30 Unless otherwise tainer, provide integrity that is equivalent to or better than
required by the manufacturer, refrigerated storage temper- the original container.
ature is between 2° and 8° C (36° to 46° F). Other common ■■ If the component has been transferred from the original
container, identify the new container with the component
storage requirements include appropriate labeling, storage
name, original supplier, lot or control number, transfer date,
off the floor, handling and storage to prevent contamination, and expiration date.
and rotation so the oldest stock is used first. ■■ Protect equipment from contamination and locate it to facili-
tate use, maintenance, and cleaning.
Compounding practices ■■ Use equipment and utensils of appropriate design and capac-
Compounding practices encompass all of the functions nec- ity.
essary to create a nonsterile compound, including selecting, ■■ When the same equipment is used for different types of drug
products, implement procedures including meticulous clean-
storing, compounding, dispensing the mixture, and moni-
ing before re-use.
toring the patient. ■■ Use only equipment and utensils with surfaces that are not
Equipment used in compounding needs to be appropri- reactive, additive, or sorptive.
ate for use, of sufficient size, and maintained as directed by ■■ Routinely inspect, calibrate (as necessary), and check
the manufacturer. Surfaces that come in contact with com- equipment used in compounding or testing of compounding
ponents must not react with the ingredients. Information preparations to ensure proper performance.
about balances, beakers, graduates, and similar devices can ■■ Inspect equipment prior to use to ensure suitability.
■■ Clean equipment after use.
be found in USP <1176> Prescription Balances and Volumetric
■■ Label the preparation container according to all applicable
Apparatus. federal and state laws, including the BUD and storage and
When possible, equipment used for antibiotics should handling information.
be dedicated to that function. Where HDs are compound- ■■ Label the preparation with the generic name and quality or
ed, equipment (such as mortars and pestles, graduates, concentration of each active ingredient, the BUD, storage
and similar items) must be dedicated for use with the HDs. conditions, and prescription or control number.
Large equipment (such as mixers) used for both non-HDs ■■ Counsel the patient or patient’s agent about proper use, and
instruct them to report any adverse event.
and HDs needs to be evaluated to ensure that cross-con- Source: Adapted from USP <795>.
tamination between compounds is avoided. Any reusable
equipment used for HDs must be decontaminated after use.
Filters need to be appropriate for the compound and of suf- Compounding for animals
ficient size. Pharmacists who compound for companion, performance,
Labeling needs to meet federal and state regulations. and food animal patients have additional responsibilities.
Labels are key to appropriate patient use, so they need to They must be familiar with the Animal Medicinal Drug
be carefully designed to promote readability and encourage Use Clarification Act of 1994 and related FDA regulations.32
compliance with medication regimens. In addition to rely- (See “Shall statements in <795> concerning animal patients”
ing on information in the USP General Notices and <17> sidebar.) Veterinarians are required by law to give caregiv-
Prescription Container Labeling, compounders can refer to the ers of food-producing animals an accurate length of time to
Institute for Safe Medication Practices’s (ISMP) document withhold treated animal tissues (e.g., meat, milk, eggs) from
Principles of Designing a Medication Label for Communi- the human food supply. This withdrawal time, or WDT,
ty and Mail Order Pharmacy Prescription Packages.31 The must be included on the label of every prescription prepared
document includes information on label format, methods for a food-producing species.
to enhance patient comprehension, use of patient identifi- Guidance documents from the American Veterinary
ers, and other practices to enhance patient safety. Labeling Medical Association (www.avma.org), the Society of Veteri-
for compounded preparations should indicate, “This is a nary Hospital Pharmacists (www.svhp.org), and the Ameri-
compounded preparation.” (See “Shall statements in <795> can Academy of Veterinary Pharmacology and Therapeutics
concerning compounding practices” sidebar.) (www.aavpt.org) provide more information.

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Stability and beyond-use dates

Shall statements in <795> concerning animal patients
■■ Possess a functional knowledge of drug regulation and
Manufacturers perform specific tests to determine the expi-
disposition for animals. ration date of their products. The products can be used until
■■ Possess a knowledge about the individual species limitation the date listed on the package, provided they are stored as
in physiology and metabolic capacity that can result in toxic- required in the labeling. This differs from BUDs used by
ity when certain drugs or excipients are used in compounded compounders, as the extensive studies are generally not com-
preparations. pleted. (See “Shall statements in <795> concerning beyond-
■■ Identify the intended use of any prescription for an animal
use dates” sidebar.)
prior to compounding.
■■ Conduct a literature search if formulations specifically devel-
oped for animals are not available to determine if a compo- Shall statements in <795> concerning beyond-use dates
nent of the formulation is toxic to the target species. ■■ Review stability factors in <1191> Stability Considerations in
■■ Include the withdrawal time on the label of every prescription Dispensing Practices.
dispensed for a food-producing species. ■■ Use your compounding education and experience.
Source: Adapted from USP <795>. ■■ Consult and apply drug-specific and general stability docu-
mentation and literature.
Compounding investigational drugs ■■ Observe the compounded preparation for signs of instability.
Pharmacists who compound investigational agents need to Source: Adapted from USP <795>.
be familiar with the additional requirements related to that
specialized function. USP <1168> Compounding for Phase 1 When the manufacturer’s information is available, the in-
Investigational Studies provides further information. formation in the package insert can be used. For example, the
BUD to use when reconstituting an antibiotic suspension is
Containers and closures listed in the product labeling (package insert). Though this is
Various factors need to be considered when assessing the sta- defined as simple compounding by <795>, the manufacturer
bility of nonsterile compounding. In addition to the stability has completed sufficient study to allow that information to
of the drug and final preparation, the container and closure be placed in the FDA-approved labeling.
system used will affect the appropriate BUD of the mixture Some compounded preparations—such as those in USP
(see “Shall statements in <795> concerning containers and compounding monographs or in peer-reviewed literature—
closures” sidebar). Several USP General Notices and General have undergone testing according to USP standards to sup-
Chapters can be used to evaluate containers and closures, port a specific BUD. However, most compounds have not
including undergone such studies, so depend on the default BUDs es-
■■ <659> Packaging and Storage Requirements tablished in <795>. (See Table 3.)
■■ <660> Containers Glass When determining the BUD for a compound, compound-
■■ <661> Plastic Packaging Systems and Their Materials of ers must consider a variety of elements:
Construction ■■ Chemical stability of the compounded preparation
■■ <671> Containers Performance Testing ■■ Drug-specific and general stability documentation and
■■ <1136> Packaging and Repackaging Single-Use Containers literature to limit the potential of a compound falling
outside the required USP strength or potency (generally,
Shall statements in <795> concerning containers ±10% of labeled content)
and closures ■■ Stability in the container
■■ Use containers and closure systems that meet USP require- ■■ Expected storage conditions
ments. ■■ Competency of compounding personnel
■■ When appropriate, obtain verification from the supplier of For a more complete reference on strength and stability
compliance with USP requirements. testing for compounded preparations, see www.usp.org/
■■ Use containers made of clean materials so the quality,
sites/default/files/usp_pdf/EN/healthcareProfessionals/
strength, and purity of the compound is maintained.
■■ Store containers and closures off the floor, and handle them strength-stability-testing-compounded-preparations.pdf.33
to prevent contamination. Unless manufacturer, USP compounding monograph, or peer-
■■ Store stock in a way that permits inspection and cleaning of reviewed literature for the specific compound is available and
the storage area. used, the default BUDs listed in <795> must not be exceeded.
■■ Rotate stock so the oldest is used first.
Source: Adapted from USP <795>.
Documentation
Four key types of documents are required for safe and con-
Monographs and other peer-reviewed literature may pro- temporary compounding (see “Shall statements in <795>
vide additional information, but use of those documents must concerning documentation” sidebar).
include the components, containers, and closures supporting ■■ Policies and procedures
use of the stability listed in the literature (see Documentation ■■ Safety data sheets
section). Unless the tests listed in monographs and General ■■ Master Formulation Records
Chapters are specifically required, compounders do not need ■■ Compounding Records
to perform the tests, but they do need to be knowledgeable Policies and procedures. Unless otherwise required by
about their function. laws, regulations, or organizational policy, documentation

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Table 3. Beyond-use dates

Type of formulation Maximum beyond-use date (BUD)
The BUD cannot exceed the expiration date of the API or any other component.
Nonaqueous formulation 6 months
Water-containing topical/dermal and mucosal liquid and semisolid formulation 30 days
Water-containing oral formulation 14 days, under refrigeration
Source: Adapted from <795>.

can be written or electronic as long as it is retrievable. Most ■■ Sources, lot numbers, and expiration dates of components
state boards of pharmacy, some states, and many organiza- ■■ Total quantity compounded
tions have record-retention policies and regulations with ■■ Names of personnel who prepared, performed quality
which the pharmacy must be compliant. control, and approved the preparation
Policies and procedures should be designed to standard- ■■ Date of preparation
ize practices. They should be reviewed at least annually and ■■ Assigned control or prescription number
whenever dictated by changes in processes or personnel or ■■ Assigned BUD
addition of new or revised equipment. Standard operating ■■ Copy of label
procedures need to be designed and clearly written to ensure ■■ Results of quality control
accuracy, quality, safety, uniformity in compounding, and ■■ Documentation of any quality control issues and any ad-
accountability. (See “Example list of policies and procedures” verse drug reactions reported by the patient
sidebar on page 61.)
Safety data sheets. Employers are required to comply with Shall statements in <795> concerning documentation
OSHA’s Hazard Communication Standard.34 Safety data ■■ Include all required elements in the MFR.
■■ Follow the MFR.
sheets (SDSs), previously known as material safety data Source: Adapted from USP <795>.
sheets, are required to be available for pharmaceuticals that
the drug manufacturer has determined to be hazardous and Quality control
that are known to be present in the workplace.35 As defined Each compounding pharmacy should have a quality assur-
in the Federal Food, Drug, and Cosmetic Act, drugs in solid, ance plan containing specific elements to indicate safety and
final form for direct administration to the patient (i.e., tab- quality of compounds mixed. Personnel training is key to
lets, pills, capsules) are exempt.36 The newer format of SDSs maintaining quality. Trends and variances from expected
presents the information in a standardized format contain- results are valuable to ensure a quality system. (See “Shall
ing 16 sections. SDSs for required medications and chemicals statements in <795> concerning quality control” sidebar.)
should be available to staff for reference when needed. USP <1163> Quality Assurance in Pharmaceutical Com-
Master Formulation Records (MFR). The MFR is designed pounding provides a framework for the elements to include
to standardize formulas. Many often refer to “recipe cards,” in a quality assurance plan. Clear policies, robust personnel
which define the ingredients and mixing instructions for training, and testing and verification of finished prepara-
compounds. MFRs contain similar content but are more com- tions should all be included in a pharmacy’s plan.
prehensive. USP <795> requires the MFR to contain
■■ Official or assigned name, strength, and dosage form Shall statements in <795> concerning quality control
■■ Ingredients and quantities ■■ Follow the MFR and complete the CR when executing the
■■ Calculations and doses compounding process.
■■ Compatibility and stability information and references ■■ Review each procedure in the compounding process.
■■ Equipment needed ■■ Check and recheck each procedure at each stage of the
process.
■■ Mixing instructions
■■ Establish written procedures that describe the tests or
■■ Label information examination conducted on the compounded preparation to
■■ Container used ensure uniformity and integrity.
■■ Packaging and storage requirements ■■ Observe the finished preparation to ensure it appears as
■■ Description of the final preparation expected.
■■ Quality control procedures and expected results ■■ Take appropriate corrective action when any discrepancies
An MFR is not required when preparing a compound are found.
■■ Establish control procedures to monitor the output and
according to the manufacturer’s instructions in the labeling. to verify the performance of compounding processes and
Compounding Records (CRs). CRs are documents that de- equipment that may be responsible for causing variability in
tail the specific compound dispensed to a particular patient. the final compounded preparation.
USP <795> requires the CR to contain ■■ Investigate and document any reported problems with a
■■ Official or assigned name, strength, and dosage compounded preparation, and take corrective action.
■■ Reference to the MFR Source: Adapted from USP <795>.
■■ Names and quantities of all components
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 CPE COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800>

Handling hazardous drugs ment to do so. Any items added need to comply with the ele-
USP <800> Hazardous Drugs—Handling in Healthcare Settings ments in <800>.
was published in February 2016 and had one errata pub- NIOSH’s Hierarchy of Controls (Figure 2) was used to
lished in May 2016. <800> becomes official on July 1, 2018. By design the controls that support safety when handling HDs.
that date, compliance with all containment requirements and The two most effective risk-limiting steps—elimination
work practices must be completed. Major elements of <800> and substitution—are generally not practical when consid-
include identification of the HDs handled in the workplace, ering compounding because the patient needs the prepara-
use of the appropriate facilities in which to store and com- tion. Protection of health care personnel then falls to use of
pound HD nonsterile preparations, and use of robust work the three other controls: engineering controls, administrative
practices to protect personnel from contamination with HDs. controls, and personal protective equipment. These three
The concepts in <800> are not new; they date from pharma- controls have been incorporated into <800> to help contain
cy guidance documents from the 1980s.37 USP <795> includes HDs and minimize their risk to health care personnel.
requirements for HDs, but much more extensive information
and requirements are listed in <800>. (See “Shall statements in Figure 2. Hierarchy of controls
<795> concerning hazardous drugs” sidebar.) Most
effective

Shall statements in <795> concerning hazardous drugs Elimination Physically remove

■ Store, prepare, and handle HDs by appropriately trained per- the hazard

sonnel under conditions that protect the health care workers

Substitution Replace
and other personnel. the hazard
■ Before preparing or handling HDs, train all personnel who
Engineering
compound in the storage, handling, and disposal of HDs. Isolate people
■ Train all personnel who perform routine custodial waste Controls from the hazard

removal and cleaning activities in storage and preparation Administrative

areas. Controls Change the way
people work
■ Comply with all applicable federal and state regulations for
disposal of HD waste. PPE Protect the worker with
■ See additional requirements in <800>. Least
Personal Protective Equipment

Source: Adapted from USP <795>. effective

Source: Graphic courtesy of National Institute of Occupational Safety

USP <800> is designed to protect health care personnel and Health.
in addition to protecting patients and the environment. It ad-
dresses but is not limited to containment and protection for Identifying the hazardous drugs handled
receipt, storage, compounding, dispensing, administration, USP <800> has a wider scope than <795>, as it is intended
and disposal of HDs. Just like <795>, it applies to all health to protect all health care personnel in all health care sites.
care personnel and all health care entities, but its scope is To ensure safety, each pharmacy must identify the HDs it
wider: from receipt of HDs in the pharmacy through dis- handles.
pensing, administration, and proper waste disposal occur- The HDs on the NIOSH list are those that are hazard-
ring in a health care setting. ous to personnel. These HDs are different from pharma-
Several NIOSH documents provided structure and sig- ceutical waste, which must be handled in compliance with
nificant content to the development of <800>. Environmental Protection Agency (EPA) requirements.39
Use of Tables 1, 2, and 3 in NIOSH’s List of Antineoplas- EPA waste—of which pharmaceuticals are only a part—in-
tics and Other Hazardous Drugs in Health Care Settings, cludes substances that are detrimental to the environment.
2016, is required by <800>.38 These are drugs that meet the Both personnel and environmental safety are important, but
definition of an HD: <800> and the NIOSH list are limited to those drugs that af-
■ Carcinogenicity fect the health of health care personnel.
■ Teratogenicity or other developmental toxicity Each entity, such as a pharmacy, must review the NIOSH
■ Reproductive toxicity list and determine the drugs on the list that are handled at its
■ Organ toxicity at low dose in humans or animals site, as well as the dosage forms of those drugs. USP <800>
■ Genotoxicity allows two options for handling:
■ New drugs that mimic existing HDs in structure or tox- ■ Handle all the drugs and dosage forms on the list with
icity all of the containment strategies and work practices listed
NIOSH’s list sorts the HDs into three tables: antineoplas- in <800>.
tics, non–antineoplastics, and those that are reproductive- ■ Perform an Assessment of Risk for those drugs allowed
only hazards. Note that not all dosage forms create the same for entity exemption, and establish and implement al-
risk; agents in final form that are not further manipulated ternative containment strategies and work practices for
may not create the same level of hazard as those that are fur- those agents.
ther manipulated or those that are APIs. Entities may add Some drugs on the list contain ingredients that may not
additional agents to their list of HDs, but there is no require- be entity exempt and must be handled with all of the contain-

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 COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800> CPE

Table 4. Identifying drugs and dosage forms eligible for an Assessment of Risk
Drugs and dosage forms that must follow all containment strategies Drugs and dosage forms that may be considered for an assessment
and work practices in <800> of risk and alternative containment and/or work practices imple-
mented
Active Pharmaceutical Ingredient of any drug on the NIOSH list Antineoplastics (NIOSH Table 1) that only need to be counted or
packaged
Antineoplastics (NIOSH Table 1) that must be manipulated NIOSH Table 2 drugs
Drugs and dosage forms that you have evaluated for exemption, but NIOSH Table 3 drugs
determined need to meet all requirements of <800>
Abbreviation used: NIOSH, National Institute of Occupational Safety and Health.

ment strategies and work practices listed in <800>. These are ■■ Dedicate a counting tray and spatula for counting HDs,
all APIs of any drug in NIOSH Tables 1, 2, and 3 and all HDs and decontaminate after use.
in NIOSH Table 1 (antineoplastics) unless the HD only needs ■■ Overwrap finished preparation in a clean, sealable plas-
to be packaged or counted. HDs that may be considered for tic bag.
an Assessment of Risk are those in NIOSH Table 1 that only Note that there is no requirement to label finished prepa-
need to be counted or packaged, or any of the HDs in NIOSH rations as hazardous for patient use.
Tables 2 and 3. (See Tables 4 and 5 in this CPE article.)
To develop an Assessment of Risk, you will need to re- Assessment of Risk requirements
view purchasing records and identify the HDs and dosage For APIs of any HD on the NIOSH list (NIOSH Tables 1, 2, and 3),
form of each one received. Once that initial list is developed, any antineoplastic that needs to be manipulated (split, crushed,
identify the reason each of the drugs is considered hazard- made into a suspension, mixed into a parenteral dosage form,
etc.), and any HD or dosage form not entity exempt through the
ous. The NIOSH list provides the reason and a link to addi-
Assessment of Risk, you must follow the containment strategies
tional references for each agent listed. Then determine what, and work practices described in <800>.
if any, manipulation needs to occur before dispensing to a For HDs and dosage forms that have been entity exempt
patient. If purchased in unit-of-use, or if only counting or through the Assessment of Risk, you may not need to follow the
packaging occurs, the packaging can be used as a contain- containment strategies and work practices described in <800>,
ment and work practice strategy in the Assessment of Risk. but you must implement alternative strategies that protect
Drugs and dosage forms selected for the Assessment of employees from exposure and define them in the Assessment of
Risk.
Risk must be reviewed at least annually, and the review and
revision documented. Several resources provide detailed in-
formation on specific drugs, dosage forms, and alternative Receiving hazardous drugs
containment and work practices.40,41 Ideally, suppliers will mark shipping containers on the out-
USP <800> requires the following elements to be evalu- side with an indication that the container includes (or is lim-
ated as each dosage form of a HD is reviewed for entity ex- ited to) HD contents. Suppliers are not health care settings, so
emption under the Assessment of Risk: they are not required to include this marking.
■■ Drug The external indication of HD content is useful in case
■■ Dosage form the shipping container or contents are damaged. The mark-
■■ Risk of exposure ing would allow the person receiving the container to recog-
■■ Packaging nize the hazard and take appropriate steps, as defined in the
■■ Manipulation pharmacy policy.
■■ Documentation of alternative containment strategies HDs may be received in negative, neutral, or normal pres-
and/or work practices sure space, but they may not be received in positive space or
Key elements are the packaging in which the HD is re- in any area designated for sterile compounding. They can be
ceived and if any manipulation needs to be done before ad- received in the regular receiving area, although designating
ministration. For each dosage form of the HD on your list, a specific area is recommended. Receiving personnel should
ask this question: Who has to manipulate this drug, and don one pair of ASTM D6978 chemotherapy gloves and must
where is the manipulation done? have other personal protective equipment (PPE) available (as
Alternative containment strategies to consider include defined in the pharmacy’s policy) in case of damaged items.
■■ Purchase in unit dose or unit-of-use.
■■ Package in a powder hood. Facilities for hazardous drugs
■■ Identify via shelf sticker or distinctive bin. Three types of engineering controls are described in <800>:
■■ Wear gloves meeting ASTM [American Society for Test- primary, secondary, and supplemental. Containment
ing and Materials] D6978 standard when counting or Primary Engineering Controls (C-PECs) are the venti-
packaging. lated devices informally called “hoods.” In most cases
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Table 5. Examples of hazardous drugs in each NIOSH table

This is not the entire list. Review the full list to determine the hazardous drugs you handle.
Table 1 (antineoplastics)
Busulfan Hydroxyurea
Etoposide Megestrol
Methotrexate Tamoxifen
Table 2 (non–antineoplastics)

Carbamazepine Methimazole

Cyclosporine Progesterone
Estrogens Risperidone

Table 3 (reproductive-only hazards)

Bosenten Fluconazole
Clonazepam Misoprostol
Colchicine Temazepam
Finasteride Warfarin
Abbreviation used: NIOSH, National Institute of Occupational Safety and Health.

for nonsterile compounding, a Containment Ventilated Assessment of Risk, HDs requiring refrigerated storage must
Enclosure (CVE, informally called “powder hoods”) is used, be stored in a refrigerator limited to HD storage, and the re-
although Biological Safety Cabinets (BSCs) can also be used. frigerator must be kept in the negative pressure area.
Laminar air flow workbenches and compounding aseptic An anteroom is not required if only nonsterile hazard-
isolators are not suitable for compounding HDs because they ous preparations are compounded, but if an anteroom is part
do not protect the operator. The Containment Secondary of the facility design, it must be positive pressure, not nega-
Engineering Control (C-SEC) is the room in which the hood tive pressure. Use of a single negative pressure lab for both
is placed. A Supplemental Engineering Control is a closed nonhazardous and hazardous compounding is not practical
system drug-transfer device (CSTD) used for compounded because all components exposed in that area would need to
sterile preparations (CSPs) when the dosage form allows. be treated as hazardous.
USP <800> recommends use of CSTDs for mixing CSPs and
requires use when administering HD CSPs when the dosage Personal protective equipment
form allows. The information on garb in <795> is limited, but PPE should
The C-PEC required for use for nonsterile HDs should be include hair covers, mask, and gloves to protect the prepara-
externally vented. If only nonvolatile HDS are used, the C- tion being compounded. The PPE described in <800> serves
PEC can instead be equipped with redundant HEPA filters. a different purpose: to protect the health care worker from
In either case, the C-PEC must be within an externally vented the potential hazards of HDs. Table 5 of the NIOSH list pro-
C-SEC. vides recommendations for PPE based on type of dosage
Unless entity exempt in the pharmacy’s Assessment of form and the function performed (dispensing or administer-
Risk, the rooms in which HDs are stored or compounded ing) and can be used to develop the pharmacy’s PPE policies.
must have four characteristics: Personnel entering the negative pressure nonsterile HD
■■ Be a room with fixed walls that is separate from nonhaz- compounding area (C-SEC) must don the following PPE after
ardous compounding performing hand hygiene:
■■ Have a negative pressure between 0.010" and 0.030" water ■■ Hair covers, including covers for beards
column ■■ Mask
■■ Be externally vented ■■ Shoe covers
■■ Have at least 12 air changes per hour ■■ Two pairs of gloves that meet standard ASTM D6978
The enclosed room and the negative pressure serve to con- (tested to withstand specific permeation challenges)
tain the potential hazards. The venting to the outside and ■■ Disposable gown designed for use with HDs (laminate
movement of air serve to remove the hazard. material, long sleeves with elastic or knit cuffs, no open-
The room should be designed as described in the Con- ing in front of gown)
tainment Segregated Compounding Area definition in PPE worn in the C-SEC must be doffed just before leaving
<800>, which describes the details and surface requirements. the negative pressure area so that potential contamination
Note that unless they are entity exempt in the pharmacy’s will not be transferred to other areas of the pharmacy. Dis-

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posable PPE exposed in the C-SEC cannot be reused. designed to detect a set of marker cytotoxic agents, such as
cyclophosphamide, doxorubicin, and platinum agents. Base-
Work practices line testing is recommended, then subsequent testing every
Performing a gap analysis is a useful method to identify 6 months.
areas of noncompliance. A standardized method to evaluate USP <800> also recommends but does not require medi-
work practices can be used for both a baseline assessment cal surveillance of individuals involved in handling HDs. A
and to demonstrate practice improvements over time.42 medical surveillance program is intended to identify trends
HDs must be handled appropriately throughout the of health issues in workers exposed to hazards. The NIOSH
pharmacy, including while receiving, storing, compound- Workplace Solutions document on medical surveillance pro-
ing, and holding for patient pickup. Work practices need vides additional details.43
to be developed to ensure safety throughout the transit of
HDs in the pharmacy, including assurance that the outside The future
of the finished preparation is free from HD contamination. USP General Chapters are under review and may be revised.
Though <800> requires personnel of reproductive capability When USP establishes a new General Chapter or revises an
to sign an acknowledgement of risk of handling HDs, most existing one, a proposed chapter is published for public com-
organizations have all personnel sign a statement. An ex- ment. All comments received are reviewed, and a determi-
ample of a form can be found at https://www.pppmag.com/ nation is made about the suggestion. A final chapter is then
documents/V8N10/CC/PDFs/HazDrugRisk_Acknowledg. published, with an official date of no less than 6 months from
pdf. the time of publication of the final chapter.
Surfaces must be decontaminated using an oxidizer in- There is an increasing emphasis on the competency of
tended for HDs. The traditional method is to use bleach fol- individuals who compound. The Board of Pharmacy Spe-
lowed by sodium thiosulfate to neutralize the bleach. Ready- cialties is considering a board certification in compounding.
to-use agents designed for HDs are available and provide a The Pharmacy Technician Certification Board is considering
more targeted approach to decontamination. After decon- an advanced certification in compounding. Education and
tamination, the surfaces need to be cleaned with a germi- training of advanced level practitioners is progressing as cer-
cidal detergent. Alcohol can then be applied if disinfection tificate programs are developed.
is needed. Compounding has been a core component of pharmacy
USP <800> recommends—but does not require—wipe practice since the profession was developed. Safe and con-
sampling to detect HDs that have escaped containment. temporary compounding practices support pharmacists’
Several companies market wipe sample test kits that are role in health care and in providing the best care to patients.

REFERENCES 12. USP compounding compendium [electronic subscription ser-

1. USP. USP <795> Pharmaceutical compounding—nonsterile vice]. https://store.usp.org/OA_HTML/ibeCCtpItmDspRte.
preparations. Second supplement to USP 40–NF 35. December 1, jsp?item=876080. Accessed June 30, 2017.
2017;675–83. 13. CDC. Multistate outbreak of fungal meningitis and other infec-
2. USP <800> Hazardous drugs—Handling in healthcare settings. Er- tions—case count. https://www.cdc.gov/hai/outbreaks/meningitis.
rata to USP 40–NF 35. June 1, 2017;1–19. html. Accessed June 26, 2017.
3. USP. Legal recognition of USP standards. http://www.usp.org/ 14. Meningitis-etc. http://meningitis-etc.blogspot.com. Accessed July
about-usp/legal-recognition. Accessed June 26, 2017. 2, 2017.
4. USP. Legal recognition—standards categories. http://www.usp.org/ 15. FDA. FDA implementation of the compounding quality act. https://
about-usp/legal-recognition/usp-us-law. Accessed July 3, 2017. www.fda.gov/drugs/guidancecomplianceregulatoryinformation/
5. The Joint Commission. Medication compounding providers. https:// pharmacycompounding/ucm375804.htm. Accessed June 26, 2017.
www.jointcommission.org/certification/mdccert.aspx. Accessed 16. FDA. Statement from FDA Commissioner Scott Gottlieb, MD, on
June 26, 2017. the importance of the Drug Quality and Security Act and over-
6. Pharmacy Compounding Accreditation Board. Compounding seeing the safety of compounded drugs. https://www.fda.gov/
pharmacy. http://www.achc.org/compounding-pharmacy.html. Ac- NewsEvents/Newsroom/PressAnnouncements/ucm564681.htm.
cessed June 26, 2017. Accessed July 2, 2017.
7. USP. USP <659> packaging and storage requirements. USP 40– 17. FDA. FDA’s human drug compounding progress report. https://
NF 35, 2017. Accessed June 26, 2017. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory-
8. USP. Pharmacopeial forum. http://www.usp.org/usp-nf/pharmaco- Information/PharmacyCompounding/UCM536549.pdf. Accessed
peial-forum. Accessed June 27, 2017. July 2, 2017.
9. USP. Clonidine. Second supplement to USP 40, 3508–09. 18. U.S. Department of Labor. OSHA Act of 1970. Section 5: Duties.
10. USP. Alprazopam compounded oral suspension. Second supple- https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_
ment to USP 40, 2642. id=3359&p_table=OSHACT. Accessed June 26, 2017.
11. USP. USP <795> Pharmaceutical compounding—nonsterile prepa- 19. CMS. Conditions for coverage & conditions of participations.
rations. Revised bulletin. www.usp.org/usp-nf/official-text/revision- https://www.cms.gov/Regulations-and-Guidance/Legislation/CF-
bulletins/pharmaceutical-compounding-nonsterile-preparations. CsAndCoPs/index.html?redirect=/cfcsandcops/01_overview.asp.
Accessed August 31, 2017. Accessed June 26, 2017.

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20. CMS. State operations manual. https://www.cms.gov/Regulations- files/usp/document/FAQs/strength-stability-testing-compounded-

and-Guidance/Guidance/Manuals/downloads/som107ap_a_hos- preparations.pdf. Accessed June 30, 2017.
pitals.pdf. Accessed June 27, 2017. 34. Occupational Safety and Health Administration. Hazard com-
21. FDA. Regulatory policy information. https://www.fda.gov/Drugs/ munication. https://www.osha.gov/pls/oshaweb/owadisp.show_
GuidanceComplianceRegulatoryInformation/PharmacyCom- document?p_table=standards&p_id=10099. Accessed June 30,
pounding/ucm166743.htm. Accessed June 26, 2017. 2017.
22. NABP. Survey of pharmacy law. Mt. Prospect, IL: National Associa- 35. Occupational Safety and Health Administration. OSHA Brief. Haz-
tion of Boards of Pharmacy; 2016. ard communication standard: Safety data sheets. https://www.
23. USP. USP–NF compounded preparations monograph. http://www. osha.gov/Publications/OSHA3514.pdf. Accessed July 1, 2017.
usp.org/usp-healthcare-professionals/compounding/compound- 36. Occupational Safety and Health Administration. Letter to CP Coe.
ed-preparation-monographs. Accessed July 2, 2017. January 3, 1994. https://www.osha.gov/pls/oshaweb/owadisp.
24. FDA. Pharmacy compounding advisory committee. https:// show_document?p_table=INTERPRETATIONS&p_id=21354. Ac-
www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/ cessed June 30, 2017.
Drugs/PharmacyCompoundingAdvisoryCommittee/default.htm. 37. ASHP guidelines on handling hazardous drugs. Am J Health-Syst
Accessed July 2, 2017. Pharm. 2006;63:1172–93. https://www.ashp.org/-/media/assets/
25. American Society of Health-Systems Pharmacists. Getting started pharmacy-practice/pharmacy-topics/pharmaceutical-wastes/
in non-sterile compounding [workbook and DVD]. Bethesda, MD: preparation-guidelines-hazardous-drugs.ashx?la=en. Accessed
American Society of Health-Systems Pharmacists; 2008. July 1, 2017.
26. Allen LA. The art, science, and technology of pharmaceutical com- 38. CDC. NIOSH list of antineoplastic and other hazardous drugs in
pounding. 5th ed. Washington, DC: APhA; 2016. healthcare settings, 2016. https://www.cdc.gov/niosh/topics/anti-
27. Murdaugh LB. Competence assessment tools for health-system neoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Accessed July
pharmacies. 5th ed. Bethesda, MD: ASHP; 2015. 1, 2017.
28. FDA. Certificates of analysis. In: Guidance for industry, Q7A good 39. EPA. Management of pharmaceutical hazardous waste. https://
manufacturing practice guidance for active pharmaceutical ingredi- www.epa.gov/hwgenerators/management-pharmaceutical-haz-
ents. https://www.fda.gov/iceci/compliancemanuals/compliance- ardous-waste. Accessed July 1, 2017.
policyguidancemanual/ucm200364.htm#P960_68414. Accessed 40. Kienle PC and Douglass K. Perform an assessment of risk to
June 27, 2017. comply with USP <800>. Pharmacy purchasing and products.
29. USP. Purified water. Second supplement to USP 40. 2017, 6719. 2017;14(3):37,39,41–2. https://www.pppmag.com/digitalmag/Main.
30. USP. <659> Packaging and Storage Requirements. Second sup- php?MagNo=181&PageNo=36#page/1. Accessed July 1, 2017.
plement to USP 40-NF 35, 2017;529–34. 41. Kienle PC. Completing an assessment of risk. In: Improving safe
31. Institute for Safe Medication Practices. Principles of designing a handling practices for hazardous drugs. Joint Commission Re-
medication label for community and mail order pharmacy prescrip- sources and BD; 2016. www.hazmedsafety.com. Accessed August
tion packages. https://www.ismp.org/tools/guidelines/labelFor- 31, 2017.
mats/comments/default.asp. Accessed June 30, 2017. 42. Kastango ES, Douglass K. USP <800> compliance study. http://
32. American Veterinary Medical Association. Extralabel drug use and www.800gaptool.com. Accessed July 3, 2017.
AMDUCA [FAQs]. https://www.avma.org/KB/Resources/FAQs/ 43. NIOSH. Medical surveillance for healthcare workers exposed
Pages/ELDU-and-AMDUCA-FAQs.aspx. Accessed July 1, 2017. to hazardous drugs. https://www.cdc.gov/niosh/docs/wp-solu-
33. Allen LV, Bassani GS, Elder EJ, Parr AF. Strength and stability test- tions/2013-103/pdfs/2013-103.pdf. Accessed July 3, 2017.
ing for compounded preparations. http://www.usp.org/sites/default/

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 COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800> CPE

CPE assessment
This assessment must be taken online; please see “CPE information” in the sidebar on page 72 for further instructions. The
online system will present these questions in random order to help reinforce the learning opportunity. There is only one
correct answer to each question.

1. What is the role of USP? 8. Which of the following is correct?

a. Enforce state regulations. a. Manufacturers and compounders assign BUDs.
b. Enforce federal regulations. b. Compounders assign expiration dates, and manufac-
c. Set standards. turers assign BUDs.
d. Define accreditation standards. c. Manufacturers and compounders assign expiration
dates.
2. USP General Chapters are d. Manufacturers assign expiration dates, and com-
a. Standards pounders assign BUDs.
b. Guidelines
c. Stretch goals 9. The document that defines how to mix, label, and
d. Outcomes store a specific compound is a
a. Compounding Record
3. USP General Chapters numbered under <1000> are b. Master Formulation Record
a. Advisory c. Recipe card
b. Enforceable d. USP standard
c. Informational
d. Guidelines 10. What is the official date of USP <800>?
a. July 1, 2018
4. What are the categories of nonsterile compounds b. January 1, 2017
listed in <795>? c. January 1, 2018
a. Cytotoxic, reproductive hazard, nonhazardous d. July 1, 2019
b. Low-, medium-, high-risk
c. Nonhazardous and hazardous 11. What is the scope of USP <800>?
d. Simple, moderate, complex a. Arrival at supplier through disposal in a patient’s
home
5. You have compounded a mixture of two convention- b. Arrival at supplier through dispensing
ally manufactured creams. No peer-reviewed stability c. Receipt in pharmacy through dispensing
information is available. What is the maximum BUD d. Receipt in pharmacy through disposal in a patient’s
you can assign? home
a. 14 days
b. 30 days 12. An Assessment of Risk is needed for
c. 180 days a. Drugs marked as hazardous by suppliers
d. Shorter of the expiration date of the two components b. Antineoplastic agents
c. All drugs that EPA determines require special
6. What organization determines the list of drugs or handling
dosage forms that are demonstrably difficult to com- d. All drugs on the NIOSH list of HDs
pound?
a. CMS 13. Which of the following can be considered for your
b. USP Assessment of Risk?
c. FDA a. Concentrated hormone liquid provided by a supplier
d. TJC b. Progesterone USP for use in a nonsterile compound
c. Progesterone USP for use in a sterile compound
7. If an ingredient does not have an expiration date, d. Methotrexate tablets received in a bottle of 100 tab-
what is the maximum expiration date you can assign lets that must be counted
to it?
a. Not more than 3 years from date of receipt 14. Which of the following PECs are suitable for com-
b. Not more than 1 year from date of receipt pounding with APIs or nonsterile antineoplastic HDs?
c. Not more than 3 years from date of opening a. Powder hood and biological safety cabinet
d. Not more than 1 year from date of opening b. Powder hood and laminar air flow workbench
c. Laminar air flow workbench and compounding
aseptic containment isolator
d. Compounding aseptic isolator and laminar air flow
workbench
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 CPE COMPOUNDING NONSTERILE PREPARATIONS: USP <795> AND <800>

15. Your pharmacy compounds with both non-HD and 18. Which of the following agents can be used to decon-
HD APIs. Which of the following is an acceptable taminate surfaces used in compounding HDs?
facility configuration? a. Alcohol
a. A negative pressure anteroom opening into two b. Germicidal detergent
compounding labs, one negative pressure and one c. Oxidizer
positive pressure d. Purified water
b. A single negative pressure compounding lab with
two powder hoods, one used for nonhazardous and 19. How often must wipe samples to detect HD contami-
one used for hazardous nation be done?
c. Two compounding labs, one negative pressure for a. Required every 6 months if compounding with
hazardous and one normal pressure for nonhazard- antineoplastics
ous b. Baseline and every 6 months
d. A single positive pressure compounding lab with c. Baseline and every 12 months
two powder hoods, one used for nonhazardous and d. No requirement, but recommended every 6 months
one used for hazardous
20. The purpose of medical surveillance is
16. What standard must gloves meet when used to com- a. To identify trends in groups of workers
pound HDs? b. To protect the employer from liability
a. ASTM D6978 c. To report trends to the national database
b. ASTM D6319 d. To address outcome of spills
c. OSHA 29 CFR 1910
d. EPA PPE

17. Which employees are required to document that they

are aware of the risks of handling HDs?
a. Pregnant employees
b. Personnel of reproductive capability
c. Women younger than age 60
d. All personnel

CPE information
To obtain the 2.0 contact hours (0.2 CEUs) of date can receive CPE credit. Please visit CPE Assistance is available Monday through Friday
CPE credit for this activity, you must complete Monitor for your statement of credit/transcript. from 8:30 am to 5:00 pm ET at APhA InfoCenter
the online assessment with a passing grade at 800-237-APhA (2742) or by e-mailing infocen-
of 70% or better, complete the evaluation, and To claim credit ter@aphanet.org.
CLAIM CREDIT at http://apha.us/CPE1017. You 1. Go to http://apha.us/CPE1017.
will have two opportunities to successfully 2. Log in to your APhA account or register as a
complete the assessment, and the questions will new user.
be in randomized order. The current policy of the 3. Select “Enroll Now” or “Add to Cart” (click
APhA Education Department is not to release “View Cart” and “Check Out”).
the correct answers to any of our CPE tests. 4. Complete the assessment and evaluation.
This policy is intended to maintain the integrity 5. Click “Claim Credit.” You will need to provide
of the CPE activity. Learners who successfully your NABP e-profile ID number to obtain and
complete this activity by the expiration print your statement of credit.

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