Varanya Chaiyaperm, RPh, PharmD is clinical assistant professor, University of Illinois College of Pharmacy.

Varanya Chaiyaperm

Pharmaceutical research and development in laboratory, with focus on medicine preparation, powder substances, and glass vials for drug formulation and testing | Image Credit: © felix_brönnimann - stock.adobe.com

Compounded pharmaceutical dosage forms may be generally described as preparations that are not commercially available from major pharma corporations. These preparations have traditionally been prepared in 503A pharmacies for identified patients; larger quantities of compounded preparations are also prepared by 503B outsourcing facilities for commercial distribution (1). Numerous dosage forms are compounded, including investigational drugs, parenteral nutrition, oncology preparations, radiopharmaceuticals, veterinary medications, and replacement commercial products during drug shortages (2-3). Individual compounded dosage forms may be prepared by pharmacists in community or hospital settings; greater scale compounding may include formulation scientists, engineers, and QA personnel in multi-facility corporations. Compounding may be completely manual or automated and may utilize electronic systems (e.g., automated compounding [ExactaMix], programmable robots [Equashield Pro], or pharmacy management [DoseEdge]). Aside from patients and clients, compounders may have relationships with other compounding organizations; (e.g., 503A hospitals may purchase compounded preparations from 503B facilities, and 503B organizations may provide clinical supplies to pharma industry.

This discussion describes an ordered process for compounding pharmaceutical dosage forms in workplace environments. The process comprises six stages generally applicable to all compounding 

.The first four stages directly address dosage form preparation, evaluation, packaging, and medical information. Stage 5 evaluates and verifies previous completed stages; stage 6 comprises dispensing/shipping to patients or clients. Individual activities within stages will vary depending on the type of compounded dosage form (e.g., sterile vs. non-sterile). Activities in stages may be done by multiple people (e.g., pharmacists, technicians, engineers, etc.).

The compounding process was developed considering academic teaching of compounding theory and practice, problem experiences in multiple workplaces, published regulatory observations, and medication error incidents. Academic compounding typically focuses on placebo formulations and techniques in a classroom or laboratory. Compounding in the workplace is much different—active drugs with specific and sometimes incompatible physicochemical properties, actual patients, emergency circumstances, imperfect facilities, incomplete information, inadequate staffing, excessive workloads, and logistics with interruptions, interferences, and other distractions. Basic activities in respective compounding stages are described; potential problems are identified; technical science, compliance, documentation, and personal responsibility are emphasized. The process builds on pharmaceutical and regulatory concepts, including Quality by Design (QbD) (4-6), Quality Risk Management (QRM) (7), and Pharmaceutical Quality Systems (8,9). Concepts described by professional pharma organizations are included (10-13). The technical responsibilities of management supporting compounding are also addressed.

This discussion assumes organization compliance with USP, federal, state, local, other regulatory, and professional certifications; 503B outsourcing facilities must also comply with pharmaceutical Good Manufacturing Practices (GMP). It also assumes availability of approved policies and standard operating procedures (SOPs) at the site. Non-technical considerations, such as drugs and supplies inventory, third-party reimbursement, personnel development, performance metrics, and other business responsibilities, are not addressed.

Table I. Pharmaceutical Compounding Process

Stage 1 comprises identification of all activities required to completely prepare the compounded dosage form and its associated final package. This includes formulation ingredients, preparation, testing, and other post-compounding activities for dispensing to patients or shipping to clients. Relevant information is integrated in stage 1. When stage 1 is completed, all activities for future performance will have been documented to guide the compounding process. Actions to minimize potential hazards (i.e., what might go wrong) are incorporated in the process. Stage 1 design provides technical and compliance consistency throughout all compounding activities. Stage 1 design activities are executed in stages 2, 3, and 4.

Dosage form identification and characterization. 

The first significant activity in the compounding process comprises evaluation of the medication order for the compounded dosage form. This includes determining the availability of commercial product fulfilling the medication order and making compounding unnecessary; using a commercial product is preferable to extemporaneous compounding. Compounded dosage forms may not be reimbursed by a third party if similar products are commercially available. If a suitable commercial product does not exist, the compounded dosage form is identified. Objectives analogous to QbD for commercial products, such as Critical Quality Attributes (CQA) and Critical Process Parameters (CPP), are noted. These are straightforward for an IV solution with a single additive; other compounding (e.g., parenteral nutrition, non-sterile formulations, etc.) are much more complex. Clear directions for the dosage form to be compounded are essential.

Concurrent with dosage form identification is verification of information relevant to compounding. Questionable, inconsistent, or otherwise problematic information must be corrected or confirmed. Technical information may be applicable throughout the compounding process (e.g., a light-sensitive drug must be correctly handled during preparation, post-compounding, packaging, shipping, and administration to the patient). Using an investigative approach can be helpful when presented with new compounding—what is known, what is not known and must be determined, and what is the desired outcome? In other words, where do you want to go and what do you need to know and do to get there? This approach will provide guidance and direction for the compounding effort. Missing information has been described as a major cause of medication events (14).

Patient information, such as patient age, weight, medical diagnosis, hepatic function, kidney function, concurrent drug therapy, and other patient factors affecting formulation and dosage, must be reviewed. Is the medication order consistent with diagnosis (e.g., methotrexate dosage for cancer vs. rheumatoid arthritis)?

Drug, excipients, primary package, and dosage

. Textbooks with example formulations provide the basis for pharmaceutical compounding (15-17)

Drugs and excipients to be used in compounding must be reviewed. FDA published a list of bulk drug substances that can be compounded (18,19); these must comply with USP/NF standards (20-24). Compounding must not include drugs withdrawn for reasons of safety or efficacy (25). Relevant physicochemical properties, solubility, stability, compatibility with excipients, and other factors related to formulation design are reviewed. Commercial products must be clearly identified (e.g., which heparin dosage strength will be used for dilutions [26]). Inactive formulation ingredients may be problematic in certain patients (e.g., lactose intolerance, dye allergy). The primary package for the compounded dosage form may be a polymeric IV bag, plastic syringe, glass bottle, or other container, some of which may be incompatible or require extra precautions (e.g., IV nitroglycerin requires a non-PVC administration set). Difficult-to-compound dosage forms identified by FDA should not be compounded (27). Biologic drugs are not compounded (28).

 Information relevant to labeling, patient instructions, secondary packaging, supply chain shipping (e.g., refrigeration, non-freezing, light protection), and related considerations is assembled. Dosage form labeling is prepared. Medication information for distribution to the patient or to 503B clients is compiled. Assembled information must consider the entire compounding process, including patient use.

The compounded dosage form to be prepared is defined based on the medication order and assembled information. Formulation ingredients, process steps, primary package, and relevant information that includes details must be clearly stated in compounding documentation. Exact formulation amounts and process steps that include potential causes of failure are critical. Each medication order should be viewed as a new order and not copied from previous documents; prior calculations must not be assumed to be correct. A specific calculations process has been described (29); calculations may also be incorporated within comprehensive compounding documentation. Calculations must be carefully executed and include written units of measure; omitting descriptive units when calculating is a common cause of error. Problematic notations (e.g., mcg, µg, µ) must be clarified. Calculations should be reviewed by a second person; verification must not be cursory (i.e., the originator is a boss or someone who “never” makes mistakes). Calculations logic, execution, and supporting information must be critically reviewed and include being watchful for number transpositions.

The compounding record, work order, batch record, etc. is the permanent record of the compounded preparation retained at the compounding site. Each compounded preparation requires some form of compounding record; a compounded IV solution with a single IV additive prepared according to an SOP will require much less detail than an oral capsule formulation with multiple ingredients and a multi-step compounding procedure. Hospital IV solutions may be recorded within a pharmacy management system or other electronic record (e.g., Epic, DoseEdge). A site SOP should provide documentation templates; a standardized template will increase process uniformity and prevent omissions and errors. The compounding record will be utilized throughout all stages of the compounding process. SOP references are noted for standardized activities; planned deviations are noted in the compounding record. Documentation may contain descriptive information, rationale, ingredients, sources, lot numbers, equipment, process information, references, labeling, patient counseling, and other content; its level of detail must be sufficient to enable an exact repeat preparation of the compounded dosage form. Document clarity is essential; multiple personnel will utilize the compounding record throughout the process. Documentation must not contain drug name abbreviations, problematic units of measure, and numeric problems, such as leading and trailing zeros; awareness of look-alike sound-alike (LASA) drug names (e.g., tetracycline HCl and tetracaine HCl) and other sources of confusion should be prospectively highlighted. Evaluation criteria used post-compounding are identified. A listing of representative compounding record topics is presented in 

. Signature/date of individuals associated with respective content throughout the compounding process is recorded in the compounding record. Compounding records are used for material traceability, adverse event investigations, skills training, and other applications. Some organizations develop a library of master formulation records for frequently prepared dosage forms.

 Stage 2 activities are also designed in stage 1. These include compounding planning followed by preparation of the compounded dosage form. Precautions for problematic activities are highlighted. Critical process techniques must be reviewed with technicians prior to compounding (e.g., particle size reduction, geometric mixing, levigation, syringe use, etc.); additional training may be necessary. Certain drugs and excipients (e.g., potent drugs, antineoplastics, hormones, peanut oil, allergens, beta-lactams [penicillins]) must not contaminate subsequent compounding and require dedicated or disposable equipment. Personal protective equipment (PPE) may be required for technician protection. Potent and dangerous drugs may require restricted access barrier systems or controlled pressure facilities. Stage 2 activities should be generally described in approved site SOPs; planned deviations are noted in the compounding record.

 Stage 3 activities are also designed in stage 1. These include physical evaluation of the dosage form (e.g., appearance, solution clarity, suspension dispersibility, topical cream absence of particulates, color, and other visuals). Dosage form evaluation must be rigorous and consistent with design expectations. Testing is specified in the compounding record; 503B preparations are submitted for analytical laboratory testing, sterility testing, endotoxin, and other GMP requirements; validated test methods are required. The label for the final dosage form is prepared; labeling must be accurate (e.g., codeine vs. codeine phosphate) without spelling or typo errors, especially in the patient’s name. The compounded dosage form is quarantined to prevent release pending dosage form approval in stage 5. Equipment and facilities must be properly cleaned per SOP; cleaning must consider physical properties of ingredients (i.e., hydrophilic vs. hydrophobic). Dedicated equipment must be identified and stored to prevent inadvertent use; use of disposables eliminates equipment cleaning issues. Drugs or ingredients requiring specialized waste disposal are identified. These activities should be described in approved SOPs; additional requirements are added to the compounding record.

Stage 4 activities include final requirements for dosage form release to patients, clients, or other recipients. Technical information for patients and clients comprises labeling, dosage, administration, verbal counseling, storage conditions, and other relevant communication. Patient information should be equivalent to that provided by pharma manufacturers for commercial products. The final package provided to the patient/client must ensure correct use of the compounded dosage form. Most activities should be identified in SOPs; deviations are noted in the compounding record. Specialized shipping or storage requirements beyond SOP stipulations are noted.

 provides examples of potential stage 1 hazards, risks, and failure modes (i.e., what might go wrong). Most critical among these are identifying critical dosage form characteristics, assembling and verifying information critical to compounding, calculation errors caused by omitting units of measure in equations, and compounding directions that are too general and non-specific. The point of Table II is to encourage prospective thinking about potential problems; personnel designing the compounded dosage form should anticipate problems and include preventive actions in compounding instructions.

. Signature/date of stage 1 responsible personnel is noted in the compounding record. Personal signature/date affirms responsibility for performance of stage 1 activities.

Figure 1: Example Compounding Record Information

Table II. Potential Compounding Problems in Stage 1

Stage 2 compounding comprises pre-work and actual preparation of the compounded dosage form per stage 1 directions. Personnel involved in actual compounding must also plan their activities for expeditious performance, especially when compounding sterile dosage forms.

 Pre-compounding activities include selecting and organizing drugs, materials, equipment, and supplies for efficient dosage form preparation. Personnel who prepare the compounded formulation must have good understanding of compounding techniques before initiating compounding. Activities involved may be conducted in a non-sterile compounding area, laminar air-flow workstation (LAFW) in a clean room environment, or other suitable controlled conditions. Compounding personnel must be dressed appropriately, including scrubs, sterile gowns, gloves, face masks, and personal protective equipment as required.

 Technician training on preparatory skills and safety considerations is conducted as needed. Technical skills to prepare compounded dosage forms will vary depending on type and complexity. Sterile dosage form compounding is high risk due to potential contamination. Non-sterile compounding requires familiarity with preparatory techniques for specific dosage forms.

 Preparations containing potent or toxic injectable drugs such as anti-neoplastics may require the use of dedicated clean rooms with differential air pressure monitoring.

 Compounding equipment must be carefully examined to ensure cleanliness before use. Certain drugs and excipients may require use of dedicated equipment (e.g., potent drugs, hormones, peanut oil, allergenic materials, beta-lactam [penicillin] drugs, and other ingredients that must not contaminate compounded dosage forms).

 PPE beyond usual garb/equipment may be required for technician safety when working with high-alert, oncology, or other hazardous drugs.

 Drugs, excipients, and required materials to be used in compounding are assembled. Compounding personnel must be watchful for similar drug names (LASA), standardized packaging, small fonts on labels, and other features potentially contributing to erroneous material selection. Assembled drugs, excipients, and required materials must be critically examined for evidence of stability issues, contamination (e.g., black specks), discoloration, insoluble material in solutions, package integrity, mold growth, expired dating, and other problems 

. Pictures of final selected materials for inclusion in permanent documentation are recommended.

 Compounding sterile formulations requires aseptic gowning, sterile needles and syringes, alcohol swabs, and other supplies. 

 illustrates a typical arrangement of sterile compounded formulation components in an LAFW. Properly executing planned activities will ensure expeditious preparation of sterile preparations, minimizing potential contamination. Real-time verification of problematic process steps is critical to ensure correct preparation of sterile dosage forms. Contemporaneous observation of sterile compounding through imbedded workstation cameras is recommended; digital photographs and other technology may also be utilized. The Institute for Safe Medication Practices (ISMP) has long discouraged the “syringe pull back method” to verify sterile product compounding (31). Compounding non-sterile formulations includes selection of ingredients, equipment, and other supplies. Equipment must be qualified, clean, and otherwise suitable for use. 

 illustrates a typical arrangement of non-sterile compounded formulation components. Real-time observation of problematic process steps is especially critical to ensure correct preparation of non-sterile compounded dosage forms; video, digital photographs, or other technology are useful for permanent records.

 The designed dosage form is then prepared. The formula, compounding procedure, and documentation as designed in stage 1 are executed. Sterile preparations require attention to aseptic techniques; non-sterile preparations must utilize technical processes specific to the individual dosage form.

 provides examples of potential hazards occurring in stage 2. The point of Table III is prospective thinking about potential problems. Most critical among these are insufficient planning of compounding activities, overlooking materials used during compounding necessitating retrieval during compounding, substandard compounding skills (especially with less-frequent or unfamiliar techniques), and aseptic technique “shortcuts.”

Signature/date of stage 2 responsible personnel is noted in the compounding record. Signature/date affirms personal responsibility for performance of stage 2 activities.

Figure 2. Intralipid 20% with damaged packaging (note black oxygen sensor), undissolved mannitol crystals, and contaminated lactose (black specks).

Intralipid 20% with damaged packaging (black oxygen sensor), undissolved mannitol crystals, and contaminated (black specks) lactose.


Figure 3. Sterile Product Compounding Planning

Figure 4. Non-Sterile Product Compounding Planning

Table III. Potential Compounding Problems in Stage 2

Stage 3 post-compounding comprises testing, other dosage form-related activities, and ancillary activities executed after completion of compounding.

 Activities directly related to the compounded dosage form described in site SOPs are completed. Deviations to SOPs are identified in the compounding record. Most important among these are the critical evaluation of the compounded preparation, submission of samples for testing, and completion of compounding documentation.

 The compounded preparation is evaluated. Visual examination of appearance, color and clarity of solutions, suspension dispersability, topical cream smoothness, absence of solids, freedom from visible foreign particulate matter, package integrity, signs of instability, and other quality attributes are evaluated; physical observation evaluation must be rigorous. 503B compounding samples are submitted for analytical testing to verify potency, sterility, stability, and other requirements identified in stage 1; testing must use validated test methods.

 Deviations, non-conformances, environmental monitoring, and other data related to the compounded dosage form are reviewed. Acceptable results are required for eventual dispensing to patients and shipping to clients.

 Compounding record documentation is completed. Compounding documentation must ensure full traceability of ingredients, processes, and equipment, and it must provide sufficient detail to enable an identical repeat preparation of the compounded dosage form. Documentation for sterile preparations is completed outside the LAFW.

. The compounded dosage form is labeled and associated technical information assembled per stage 1 directions.

 The compounded dosage form is quarantined until all testing is completed and reviewed.

 Ancillary activities include workspace and equipment cleaning and waste disposal. If dedicated equipment is used for specific ingredients, it must be cleaned, dried, labeled, and appropriately stored to prevent future inadvertent use; misuse of dedicated equipment is a common compounding error. Waste disposal must follow site procedures (i.e., “sharps,” recyclables, HIPAA, biologicals, oncology drugs, and drug waste disposed into appropriate containers). Routine post-compounding activities are completed per SOPs. Deviations from SOPs are noted in the compounding record.

 Examples of possible stage 3 hazards are presented in 

. The point of Table IV is prospective thinking about potential problems. A common stage 3 problem is dosage form evaluation; preparations must strive for excellence and not be just “good enough.” Equipment used in compounding must be scrupulously cleaned after use. Dosage forms must be quarantined to prevent release until final approval (stage 5),

Signature/date of stage 3 responsible personnel is recorded in the compounding record. Signature/date affirms personal responsibility for stage 3 activities.


Table IV. Potential Compounding Problems in Stage 3

Stage 4 final package comprises technical and associated activities that complete dosage form preparation. Supportive information for patients or clients is compiled as specified in stage 1.

Test results are compiled and evaluated. Failing or unexpected test results must be investigated, appropriate action taken, and corrective action implemented. Labeling, medication information, patient counseling, and other communication to be provided to patents and clients is compiled. Commercial product manufacturers provide medication information to patients; comparable information should be developed on patient/client interactions. ISMP Medication Learning Guides for Consumers exemplify drug information provided to patients at dispensing (34). The compounded dosage form must be used correctly by the patient to ensure efficacy.

Associated activities are identified in an SOP or specified in the compounding record. Deviations to SOPs may include specialized protective packaging, time/temperature limitations with tracking devices, and other shipping requirements. Shipping should be performed by a dedicated delivery service in a controlled manner with location-tracking capability; shipping must include temperature control.

. Compounding record documentation is finalized. This is the final compounding record retained by the organization. After the compounded dosage form is dispensed or shipped, the compounding record is the lasting evidence of compounded dosage form preparation.

 Examples of possible stage 4 hazards are presented in 

. The point of Table V is prospective thinking about potential problems. Most important among these are assembly of communication for patients and clients. The compounded dosage form must be used properly by the patient, administered correctly, and otherwise handled to be efficacious. Completion of documentation is also critical in stage 4. Compounded dosage form quarantine (stage 3) should prevent inadvertent release to patients or clients.

Signature/date of stage 4 responsible personnel is recorded in the compounding record. Signature/date affirms personal responsibility for stage 4 activities.

Table V. Potential Compounding Problems in Stage 4

Stage 5 verification is the final check on the compounded dosage form, packaging, documentation, and related information before dispensing to the patient or shipping to clients.

Review of the completed dosage form and associated elements is a critical step in the compounding process. Ideally, verification is accomplished by an independent observer separate from people involved in the compounding process. Verification addresses the final dosage form, test results, completed documentation, and associated communications to be provided to patients or clients. The compounded dosage form is not dispensed to patients or shipped to clients until the final compounded dosage form and associated information are approved.

Review by a competent, independent observer must be a serious and thorough activity by an impartial observer—not a perfunctory ”rubber stamp” exercise. ISMP has discussed the judicious use of independent double-checks in pharmacy practice (35). Final dosage form and associated information must be reviewed vs. the original medication order. Review must be completed before the compounded dosage form is dispensed or shipped. Checklists are useful to ensure a comprehensive review. Errors, omissions, or insufficient details in compounding documentation are corrected. Documentation will be utilized in future investigations, training, and other applications. Final documentation is retained in prescription files, patient records, manufacturing batch records, or electronic systems. An example checklist with relevant topics is provided in 

When dosage form appearance, test results, documentation, and other reviewed content are acceptable, the compounded dosage form is approved for release by the responsible pharmacist. Approval is documented in the compounding record. The dosage form is removed from quarantine.

Examples of possible stage 5 verification hazards are presented in 

. The point of Table VI is prospective thinking about potential problems. Potential hazards in stage 5 are critical; this is the final check of dosage form quality, test results, patient/client documentation, and compounding record documentation. Compounding record documentation is the lasting record of the compounding process.

Signature/date of stage 5 responsible personnel is recorded in the compounding record. Signature/date affirms personal responsibility for stage 5 activities.

Figure 5. Example Compounding Verification Checklist

Table VI. Potential Compounding Problems in Stage 5

Stage 6 comprises activities in which compounded dosage forms are provided to users.

Dispensing/shipping to patients/clients. 

Stage 6 includes dosage form dispensing to patients, providing drug information, and counseling as needed. Dispensing and counseling are performed according to the clinical situation and patient needs. Stage 6 also includes shipping to patients per secondary package design, including temperature control, light protection, package tracking, and other requirements. Approval to dispense/ship is documented in stage 5; dispensing or shipping must not occur before the responsible pharmacist has provided final dosage form approval. Stage 6 also includes shipping to clients per secondary package design after responsible pharmacist approval.

Numerous examples exist of drug products being dispensed to the wrong patient and conditions under which this may occur. Errors may occur in community settings or in the hospital environment for a variety of reasons. Obvious causes involve patients with identical last names. Hospitalized patients may switch beds without notifying the nursing staff. Electronic order entry may be confused; mis-transcribed telephone orders, dispensing system overrides, and other potential patient mixups may occur. Verification using two patient identifiers is recommended to confirm the intended patient as well as verify correct treatment to the individual. These actions should occur at each step in the medication process (i.e., from original medication order, through multiple transcriptions {physicians, pharmacists, nurses}, and final dosage form administration to the patient). Examples of questions to be asked before drug administration, dispensing, or counseling to verify they are the intended patient typically include the patient’s name, date of birth, last four digits of the US social security number, or other government identification. Only verifying the patient’s name is not sufficient. Patients for whom English is a second language require increased assurance that they are the intended patient.

 Stage 6 also includes shipping to clients per secondary package design. Approval to dispense/ship is documented in Stage 5; again, dispensing or shipping must not occur before the responsible pharmacist has provided final dosage form approval.

Examples of possible stage 6 hazards are presented in 

. The point of Table VII is prospective thinking about potential problems. Most significant among these are dispensing a drug to the wrong patient. This may occur in community and hospital settings; there are numerous opportunities for actions that contribute to dispensing/administration of dosage form to the wrong patient (36-38).

 Signature/date of stage 6 responsible personnel is noted in the compounding record.Signature/date affirms personal accountability for stage 6 activities.


Table VII. Potential Compounding Problems in Stage 6

Management of a compounding organization is responsible for daily compounding performance, as well as related supportive activities. Quality systems guidance documents identify expectations of management (e.g., leadership, structure, quality system design, policies, objectives, plans, system review). FDA issued CDER’s Quality Management Maturity Program (39) addressing expectations beyond current GMP; compounding management must aspire to much more than minimal GMP compliance. Development of a quality culture mindset in which risks to compounded product quality are minimized is led by management (40)and should be forefront in the organization. ICH Q9(R1) QRM addresses “What might go wrong?” and describes common methods of risk assessment; these methods are directly applicable to pharmaceutical compounding.

Primary management responsibilities in compounding organizations include the following:

 Hiring capable personnel is the most important function of management. Compounding personnel must have appropriate technical compounding skills; organizational skills, self-discipline, attention to detail, language skills, legible handwriting, common sense, and realization of personal deficiencies (i.e., knowing what you don’t know) are desirable. Interpersonal skills in a teamwork environment are essential. Sufficient number of personnel must also be hired commensurate with workload.Management is also responsible to assure that each staff member knows and understands their roles and responsibilities, as well as accepts personal responsibility for performance.

 Management is responsible for the standards that define daily workplace activities. Compounding organizations must have written and approved documents; compliance with these documents is mandatory. Inadequate procedures, training, and non-compliant performance are always among the most frequent GMP violations in pharma (41). SOP compliance must be forefront in compounding organization performance. SOPs should be living documents, periodically reviewed for accuracy and relevance and updated when new information is available.

Personnel must be trained and periodically re-trained on SOPs. Training must be documented; if not documented, it didn’t happen. Training must emphasize personal accountability for SOP requirements; personnel must understand that their signature/date in compounding documentation affirms personal responsibility.

 The workplace environment must encourage communication of problems, mistakes, and issues without fear of punishment or embarrassment. Management must develop a collaborative relationship with staff with ongoing focus on quality (i.e., a true quality culture that is evident in personnel performance). ISMP identified communications about medication safety risks occurring within and outside the organization as best practices for community (42) and hospital pharmacy (43). FDA-483 observations and warning letters demonstrating compliance deficiencies in compounding organizations are readily available (44).

Beyond hiring, procedures, and training are the everyday expressions of management commitment to quality. Management focus must expand from traditional management to include anticipation of performance hazards and risks (i.e., what might go wrong). Management daily performance in routine activities must exemplify commitment to quality.

 Management is responsible for administrative functions supportive to compounding (e.g., funding, scheduling, maintenance, calibration, facility cleanliness).

Examples of possible management hazards are presented in 

. Most significant among these are deficiencies in management commitment to responsibilities; organization culture is directly related to management commitment. The actions of individual employees reflect the attitude and commitment of management—what management wants, management gets. Management is also ultimately responsible to address potential hazards identified above in respective stages of the compounding process.

 Signature/date of management on policies, procedures, and other documents affirms management accountability.


Table VIII. Potential Compounding Problems by Management

This discussion describes an ordered process for pharmaceutical compounding based on academic teaching of compounding theory and practice, problem experiences in multiple settings, regulatory observations, and published medication errors. Technical activities occurring in the compounding workplace beyond physical compounding techniques are addressed. The process describes what and why activities, as well as what might go wrong throughout the comprehensive process.

Six stages of compounding activities are identified, each having specific objectives. Stage 1 design activities address considerations to be executed in all subsequent compounding stages; technical consistency throughout the process is forefront. Compounding activities are executed in stages 2, 3, and 4. Stage 2 comprises selection of materials and equipment, compounding planning, and actual dosage form preparation. Stage 3 post-compounding comprises dosage form review, sampling, testing, and related activities. Stage 4 includes final review of test results; medical information and packaging for dispensing to patients or shipping to clients is compiled. Stage 5 verification comprises review of the compounded dosage form, labeling, drug information, and secondary packaging; stage 5 activities require an independent observer. The compounded medication is approved for dispensing in stage 5. Stage 6 dispensing/distribution provides the compounded dosage forms to users, including patient counseling, medical information, and/or appropriate supply chain shipping. Compliance with regulations and site procedures is required throughout the process. Personnel understanding of their responsibilities and affirming accountability by signature/date on documentation is required. Examples of potential hazards are identified throughout; case studies further demonstrate problematic circumstances.

Management has significant technical responsibilities in the compounding process. Management is responsible for the actual compounding, as well as for supportive functions. Management must continually support employee training and awareness of possible problems. As risks are identified and knowledge is gained, SOPs are modified, including corrective and preventive actions for continuous improvement. A workplace environment in which quality is forefront (i.e., a quality culture) must be an ongoing goal of compounding management and staff.

Pluta, P.L. Pharmaceutical Compounding Overview – Technical, Regulatory, and Management in a Workplace Environment. 

Compounding Overview: Primary Considerations for the Workplace (pharmtech.com)

https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm

Articles

An ordered pharmaceutical compounding process for use in 503A pharmacies, 503B outsourcing facilities, pharmaceutical industry, and other applications.

Dosage Form Compounding in the Workplace Environment

compounding pharmacist at work 2 | Image Credit: ©Nadia -stock.adobe.com

Drug calculations for the formulation of dosage forms and associated preparations are key activities in pharmaceutical compounding. Calculations determine the amount of drug identified in the request for compounding. Correct drug calculations for compounded preparations are essential; if drug calculations are incorrect, resulting preparations will be incorrect—potentially with significant therapeutic and technical consequences.

This paper is the first in a series of discussions that address drug calculations and related topics for small-molecule compounding. Series discussions are applicable to essentially all compounding in 503A pharmacies, 503B outsourcing facilities, pharma industry R&D including clinical drugs, non-product laboratory preparations, and other applications. Series discussions will reflect academic teaching and compounding practice experiences. Textbooks traditionally provide the foundation for calculations (1–3); content in this paper addresses workplace applications and potential hazards (i.e., what might go wrong?) (4). Concepts that are often omitted, confused, or otherwise misunderstood that affect the accuracy of calculations are described. Topics address small-molecule compounding; large-molecule biologic drugs are not compounded (5,6).

Part one in the series addresses terminology, regulations, and labeling respective drug types. Subsequent topics will include numeric calculations, moisture, material losses, and related topics that build on prior publications (7,8). Drug calculations begin with the medication order—individual prescription, hospital order, 503B outsourcing batch, pharma clinical supply request, research formulations, or other request for a compounded preparation. The medication order identifies the desired active moiety by proprietary or generic name along with the duration of treatment. Types of drugs used in compounding are identified. Compounding personnel must select an appropriate drug for compounding—there may be multiple choices—and calculate its amount. Drug selection must integrate patient considerations, physicochemical properties, material handling, and other applicable considerations. After drug selection, calculations are executed; each drug requires different calculations. Post calculations, labeling must clearly define the compounded preparation. 

 shows an overview of calculations-related activities from medication order initiation through final dosage form dispensing and/or shipping; specific part one discussion topics are highlighted in red.

 Drug calculations process. (Figure courtesy of the authors)

 Drugs are known by a variety of terms depending on regulatory agency, country, site vernacular, and other considerations. Some of the more familiar terms include API, active substance, drug substance, bulk drug, bulk drug substance, active, bulk, and so on. “API” terms are more common in pharma industry (e.g., International Council for Harmonisation (ICH) Q7A 

Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients

 [9]); “bulks” language is common in compounding discussions (e.g., Bulk Drug Substances Used in Compounding Under Section 503A of the US Food, Drug and Cosmetic Act (FD&C Act) [10]; Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act [11]).

. The active moiety is the part of the drug responsible for pharmacologic activity. In theory, the active moiety excludes molecule portions such as esters, counterions, complexes, chelates, clathrates, and waters of hydration that do not contribute to drug activity. The active moiety is contained within the drug molecule

it may be part or all of the molecule (e.g., diazepam is generally considered to be the active moiety and active drug in Valium). The distinction between active moiety and active drug is critical for understanding calculations and labeling in salt drugs.

. This discussion identifies several drug types relevant to compounding calculations; these are categorized per chemical structure as non-salt drugs and salt drugs. Non-salt drugs are also termed free acids or free bases; non-salt drugs have covalent and other non-ionic bonds. For compounding purposes, the active moiety of a non-salt drug comprises the entire drug molecule (i.e., active moiety is same as active drug).

Salt drugs are molecules with ionic bonds. Salt drugs are easily recognized by name (e.g., sodium drug, potassium drug, drug hydrochloride, drug acetate, and others that include counterions). Some non-salt drugs may be confused as salts (e.g., clindamycin phosphate is an ester; clindamycin palmitate hydrochloride is a salt of an ester). Reviewing the molecule structure is essential to determine the drug type. Some drugs may be available as either non-salt (covalent) molecules or as salts (e.g., phenobarbital and sodium phenobarbital; codeine and codeine phosphate), and either may be used in compounding with appropriate evaluation; their respective properties (i.e., pharmacologic and physicochemical) must be considered.

 Another type of salt drug, policy-exception salts, has also been identified. These molecules are specified in the 

/FDA salt policy and are dosed differently than salt molecules. Policy-exception salts require different calculations and labeling than salt drugs that comply with policy. Recognizing salt molecule structures is also important in electrolyte calculations.

. Peptides may be small-molecule drugs or biologics depending on their amino acid chain length (<40 amino acids are small molecules; >40 amino acids are biologic proteins). Peptides have covalent bonds between amino acids as well as ionizable groups and salts. FDA is currently reviewing data to definitively classify peptides within compounding bulk lists (12,13).

 This discussion also identifies several drug forms relevant to compounding calculations. Forms describe the concentration of drug moiety in the drug. Forms may be bulk solids assumed to be essentially 100% potent or pure; pharma industry and 503B outsourcing facilities commonly use bulk drugs for compounding. Forms may also be drugs at some concentration in solid or liquid mixtures; 503A hospital and community pharmacies are more likely to use drug mixtures (e.g., commercial sterile IV additives and commercial tablets) as drug sources for individual unit compounding. Commercial products used in compounding also contain functional formulation ingredients (filler, binder, coating, flavor, color, etc.) (14).

These ingredients must be evaluated before use; they may cause undesirable effects on patients (e.g., allergic reactions, lactose intolerance), be restricted by religious beliefs (15), or have incompatible physicochemical properties. Part two in this series will address numeric bulk drug calculations; part three will address numeric drug mixture calculations.

 The atomic mass (atomic weight) is the mass of an individual element expressed in atomic mass units (amu) or daltons (Da) (e.g., sodium = 22.99 amu). Atomic masses represent protons and neutrons in the atom structure; the atomic number represents protons; atomic mass decimals represent atom isotopes. The molecular mass (molecular weight) (MW) of a compound is the combined masses of individual elements, hydrates, solvates, and other molecule components (e.g., sodium chloride MW = Na + Cl = 58.44 amu). The active moiety molecular mass may be calculated based on the atomic weights of the individual elements in the active moiety. Also relevant is the number of active moiety components in the drug molecule (e.g., divalproex sodium contains two valproic acid active moieties). The molecular masses of the active moiety and drug are correlated to their respective gravimetric weights by calculating moles (mols) and millimoles (mmols). A mole is the weight in grams of the drug molecular mass (e.g., 58.44 grams = 1 mole of NaCl; 58.44 mg = 1 mmol of NaCl). Understanding moles is important to determine equivalent dosages of different drug salts.

 The most relevant drug name in compounding is the non-proprietary name. The non-proprietary name is the generic name of the drug; diazepam is a non-proprietary name. Non-proprietary names are approved by country regulatory agencies and the World Health Organization (WHO) and usually include a drug-name stem; (e.g., -caine [local anesthetics], -olone [steroids], and many others) (16). Proprietary drug names are commercial marketing names; Valium is a proprietary name.

 Pharmaceutical alternatives are drugs that have the same active moiety but are a different molecule (i.e., different salts or esters). Metronidazole is an active moiety; metronidazole hydrochloride and metronidazole benzoate are pharmaceutical alternatives. The same moles of pharmaceutical alternatives have the same pharmacologic effect (e.g., same moles of codeine, codeine sulfate, and codeine phosphate have different gravimetric weights but same pharmacologic effect). Pharmaceutical alternatives used for compounding must be approved drugs—not unapproved synthetic salts. Different drug salts may have different properties (solubility, pKa, lipophilicity, hygroscopicity, others [17]); substituting pharmaceutical alternatives requires evaluation of respective physicochemical properties. Pharmaceutical alternative dosages are determined using molarity calculations. Prodrugs are related but are different chemical compounds; prodrugs per se are not pharmaceutical alternatives; prodrugs are compounds that convert to an active moiety drug in the body.

Several other similar terms may be confused or misused when discussing pharmaceutical alternatives. Pharmaceutical equivalents are generic drugs—same drug, same dose, same route of administration, but different appearance. Therapeutic equivalents are the same as pharmaceutical equivalents (generic drugs) that have been tested for bioequivalence. Therapeutic alternatives, therapeutic interchange, and therapeutic substitution are related terms associated with drug substitution with same clinical effects as authorized through a hospital formulary (18).

There are numerous regulatory documents addressing product naming, dosage, and labeling for commercial products that are relevant to compounding (19,20). Respective 503A and 503B bulk drug lists identify approved drugs. Specific compounded dosage form labeling requirements are exempt from FD&C regulations identified in Section 503 (21). 503B compounded preparations must state “This is a compounded preparation” or similar wording (22). Selection, naming, and labeling of compounded dosage forms containing non-salt (covalent) active moieties/drugs is straightforward (23–25); non-salt active moieties are generally identical to their drug. Selection, naming, and labeling of compounded dosage forms containing active moieties that are salt molecules is more complex.

is the basis for FDA guidance (27,28) on calculating and naming salt drugs. The FDA guidance states:

“1. When a drug in a drug product is a salt, the drug product monograph title will contain the name of the active moiety (or neutral form) and not the name of the salt (e.g., ‘newdrug tablets’—not ‘newdrug hydrochloride tablets’).

2. The strength also will be expressed in terms of the active moiety (e.g., ‘100 mg newdrug’) rather than the salt strength equivalent (e.g., ‘123.7 mg newdrug hydrochloride’).

3. If the name and strength of a drug product are expressed in terms of the active moiety, the full name and full strength (or proportion, if CDER [Center for Drug Evaluation and Research] has determined proportion is more appropriate) of the drug (e.g., salt) will appear elsewhere on the drug product label and labeling.

4. The USP Salt Policy provides for exceptions to the ‘active moiety’ naming approach when the name of the salt conveys vital information from a clinical perspective. In these cases, the drug product monograph title will include the name of the salt, and the strength of the drug product also is expressed in terms of the salt form (drug).

5. USP does not anticipate changing existing monograph titles unless necessary for safety. USP and FDA have agreed to coordinate regarding any necessary retrospective name changes.”

FDA expects that new chemical entities that are salts will be named using the active moiety in accordance with the USP Salt Policy described above. However, the FDA guidance also identifies exceptions (#4 above) to this approach. Therapeutic and historic reasons are cited as justification for exceptions. Many historic drugs were dosed according to their drug weights including counterions (e.g., atropine sulfate, codeine phosphate, morphine sulfate). The following are salt drug policy-exceptions per FDA guidance (28):

Drug is a simple salt and administration is therapeutically important (e.g., lithium carbonate, iron sulfate and other intravenous iron, calcium gluconate and other calcium salts, potassium chloride, magnesium sulfate, and other common intravenous additives).

Scientific evidence demonstrates the salt form affects the absorption, distribution, metabolism, and excretion (ADME) that influences product selection.

Clinically significant amounts of cations (sodium, potassium, magnesium, calcium) accompany the active moiety of a drug product related to the daily electrolyte intake in special populations (e.g., sodium in cardiac treatment and potassium in renal treatment).

There is significant evidence-based safety concern that the counter-ion part of the salt could cause acid-base disturbances; hepatic, renal, or other organ damage; or hypersensitivity reactions.

The name of the salt is necessary to maintain consistency with other dosage forms of the same drug (salt). For example, drug products approved before 2013 with the salt in its established name and dosage based on the salt form would not change naming for a new dosage form with the same salt drug.

The USP Salt Policy should not be applied if there are relevant, documented safety reasons in a closely related product.

Compounded dosage forms are exempt from commercial product labeling requirements. 503A compounded dosage form labeling is also governed by state pharmacy regulations. Accurate compounded product labeling requires attention to detail (i.e., labeling “codeine” is not the same as labeling “codeine phosphate”).

The labeling of covalent compounded preparations is straightforward. Covalent active moieties are often the drugs in compounded dosage forms. The stated amount of drug must clearly identify the name and drug amount (e.g., Diazepam 10 mg tablets). Approved commercial product labeling containing the compounded drug may be checked to verify equivalence of active moiety and drug in labeling.

FDA guidance documents illustrate labeling of dosage forms containing salt drugs. The following examples illustrate the compounding dilemma involving salt drugs—are salt drugs labeled according to their active moiety or bulk drug? 

illustrates a salt drug label with active moiety as drug name. This label represents product in compliance with the drug salt policy (i.e., active moiety is the focus of compounding and associated calculations; ionic non-active counterions are in secondary labeling). Labeling of this type would have been approved after USP salt policy was implemented. Note active moiety on primary label and the drug (larger number) on side panel of label. Naming and labeling of salt drugs is applicable to compounded dosage forms.

Salt drug dosage form label–active moiety drug name. Note active moiety on primary label; side panel provides bulk drug calculation

 illustrates a policy-exception salt drug label with drug notation on the primary label and active moiety calculation in the side panel (i.e., opposite of 

). This label demonstrates labeling for a pre-2013 approved salt drug product—the entire salt drug amount (Olddrug palmitate) is dosed as the active moiety per USP salt-guidance exceptions. This approach is applied to compounded dosage forms involving drugs identified as exceptions to the salt policy.

Policy-exception salt drug dosage form label–bulk drug name. Note bulk drug name on primary label; side panel provides active moiety calculation. (Figure courtesy of the authors).

Several considerations are potential hazards to drugs selection, calculations, and labeling in compounded dosage forms. Understanding drug chemistry is fundamental. Misunderstanding of the USP salt policy causing dosage errors and labeling errors is an obvious problem. Labeling on approved commercial products may not be consistent with examples described previously.

Compounding personnel involved with the selection of drugs for compounding must have a good understanding of basic drug chemistry; molecular masses, moles, structures, and associated topics are relevant in compounding calculations. Selection of a drug is critical; molecule physicochemical properties may be relevant to compounding (e.g., valproic acid is an insoluble oil and divalproex sodium is a water-soluble solid). The choice of drug and evaluation thereof must be based on technical judgment. Regulations addressing drugs in compounding are also noteworthy; FDA has cautioned regarding use of semaglutide (Ozempic), semaglutide sodium, and semaglutide acetate; the aforementioned salt forms are not FDA-approved (29,30). FDA has also reminded compounding organizations to utilize sterile drugs when compounding sterile dosage forms (31).

 Drug information and labeling may be confusing, inconsistent, or have unusual formats; approved labeling may have been formatted before the USP salt policy became official. Practitioners may incorrectly assume differences between active moieties and drugs are inconsequential; drug dosage errors in salt drugs will depend on the respective molecule masses of active moiety and counterion. Worst-case molecule structure affecting dosing would be a small molecular weight active moiety and a large inactive counterion (sulfate, phosphate, mesylate, etc.). Depending on drug properties, even small-molecule counterions (hydrogen, sodium, potassium) may be significant; the phenytoin package insert cautions that phenytoin and sodium phenytoin have an 8% difference in dosage effects (32). Even when clinical effects are calculated to be minimal; calculations will be incorrect if the counterion molecular weight is overlooked.

 Drug overdoses occur when a drug exception is erroneously calculated to provide the active moiety amount as directed by the USP salt policy (i.e., salt policy is followed when it is not appropriate). For example, if codeine 30 mg was ordered and codeine phosphate drug amount was calculated as a new drug, the codeine phosphate calculated value (40 mg) would be 33% high. Codeine analgesic dosage historically has utilized 30 mg codeine phosphate or codeine sulfate—not codeine base (33,34).

. Drug underdoses occur when the drug is utilized as the active moiety without calculating the equivalent active moiety amount. For example, if clopidogrel 75 mg was ordered for compounding, but clopidogrel bisulfate was used, the clopidogrel active moiety dose (58 mg) would be 23% low.

Individual compounded dosage forms must be correctly labeled reflecting the active moiety and drug content. Labeling “codeine” when dosage and content is “codeine phosphate” is not accurate. Label space limitations may encourage labeling shortcuts that are inaccurate and incorrect. The Institute for Safe Medication Practices (ISMP) has identified labeling problems in compounded dosage forms and has recommended increased FDA guidance on compounded dosage form labeling (35). Drug shortages causing purchase of uncommon concentrations (e.g., heparin) have contributed to errors including fatalities 

 when personnel do not recognize concentration changes and do not recalculate drug amounts.

 Compounding personnel must be wary of inconsistent, confusing, or non-standard formats in labeling (

) that do not follow the FDA format described above. For example, metoprolol tartrate (Lopressor) is an immediate-release beta blocker that is dosed twice daily; metoprolol succinate (Toprol XL) is an extended-release metoprolol preparation formulated for once-daily dosage. Secondary labeling on metoprolol succinate products (37–39) references metoprolol tartrate to aid in transitioning patient dosage. Potassium phosphates injection (policy-exception drug) is labeled as phosphorus mmol/mL and potassium mEq/mL on the primary label and mg/mL amounts of potassium phosphate monobasic and potassium phosphate dibasic equivalent amounts of potassium and phosphate on the side panel (40,41). Succinylcholine labeling may be inconsistent or different format (e.g., same concentration products may be labeled as total drug mg/vial (42–44). These labels were likely approved before the salt policy was implemented and have not been updated.

Part one of this series addresses pharmaceutical principles including terminology, regulations, and dosage form labeling in compounded preparations. Types of drugs are identified. Non-salt (covalent) drugs and salt (ionic) drugs are primary groups; certain salt drugs are further grouped as policy-exception salts. Policy-exception salts are dosed as non-salt drugs including their molecule counterions; labeling must identify the equivalent active drug amounts. Forms of drugs are also identified. Drug formsmay be solids or liquids; they may be bulk drugs or drugs in mixtures; mixtures may include solutions, mixtures of solids, and commercial products (e.g., tablets). 

 summarizes the drug types, dosage rationale, forms, active moiety identification, primary labeling, and secondary labeling. The USP salt policy, historical precedent, and identified exceptions are the bases for these requirements; note significant labeling differences between salt drugs and policy-exception salts. Problems associated with the above are identified. Effects resulting from misunderstanding of drug salt principles may include overdosing or underdosing of dosage form active moiety. Mislabeling of dosage form content is also possible; attention to detail is critical. Labeling may have variations for a variety of reasons. Careful reading of commercial product labeling with good understanding of principles is mandatory for compounded product applications.

503A pharmacy labeling is also regulated by state agencies.

 edition. Wolters Kluwer/Lippincott, Williams, & Wilkins, Philadelphia, PA, 2013.

 edition. John Wiley & Sons, Hoboken NJ, 2017.

Pharmaceutical Compounding Calculations in The Art, Science, and Technology of Pharmaceutical Compounding

 ed. American Pharmacists Association, Washington, D.C., 2020.

https://database.ich.org/sites/default/files/ICH_Q9%28R1%29_Guideline_Step4_2023_0126_0.pdf

ASHP. Compounding Frequently Asked Questions. ASHP.org. September 2016. 

https://www.ashp.org/-/media/assets/advocacy-issues/docs/compounding-guidances-frequently-asked-questions.ashx?la=en

FDA. Compounding and the FDA. Questions and Answers. FDA.gov. Nov. 15, 2024. 

https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers

Pluta, P.L. Compounding Overview: Primary Considerations in the Workplace. 

https://www.pharmtech.com/view/compounding-overview-primary-considerations-in-the-workplace

Pluta, P.L.; Mancini, A.M.; Thakar, N.B.; and Chaiyaperm, V. Pharmaceutical Compounding Calculations in the Workplace Environment. 

https://www.pharmtech.com/view/pharmaceutical-compounding-calculations-in-a-workplace-environment

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q7a-good-manufacturing-practice-guidance-active-pharmaceutical-ingredients

FDA. Bulk Drugs Used in Compounding Under Section 503A of the FD&C Act. FDA.gov. Sept. 26, 2024. 

https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act

FDA. Bulk Drugs Used in Compounding Under Section 503B of the FD&C Act. 

https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503b-fdc-act

Alliance for Pharmacy Compounding. Understanding Law and Regulation Governing the Compounding of Peptide Products, March 1, 2024. 

https://join.a4pc.org/hubfs/PDFs/APC-Peptides-Statement-March-1-2024.pdf?hsLang=en

FDA. Bulk Drug Substances Nominated for Use in Compounding under Section 503A of the Federal Food, Drug, & Cosmetic Acid, 9-20-23. 

503A Categories Update for September 2023

Pravastatin Pharmaceutical Compositions Having Good Stability. US patent 5180589A, 1991. 

https://patents.google.com/patent/US5180589A/en

Khokhar, W. A Dein, S.L. Qureshi, M.S., Hameed, I., Ali, M.M., Abbast, Y.; and Sood, R. When Taking Medicine May Be a Sin; Dietary Requirements and Food Laws in Psychotropic Prescribing. BJPsych Advances, Cambridge University Press, V21, #6,2 January 2018. 

https://www.cambridge.org/core/journals/bjpsych-advances/article/when-taking-medication-may-be-a-sin-dietary-requirements-and-food-laws-in-psychotropic-prescribing/5E1A5178CD8AEF2915B852316CFEE305

The Use of Stems in the Selection of International Non-Proprietary Names (INN) for Pharmaceutical Substances 2018

https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/stembook-2018.pdf?sfvrsn=32a51b3c_6&download=true

Gupta, D.; Bhatia, D.; Dave, V.; Sulanya, V.; and Gupta, S.V. Salts of Therapeutic Agents. 

ASHP. Guidelines on the Pharmacy and Therapeutics Committee and the Formulary System. American Society of Health System Pharmacists. 2021. 

https://www.ashp.org/-/media/assets/policy-guidelines/docs/guidelines/gdl-pharmacy-therapeutics-committee-formulary-system.ashx

FDA. FDA’s Labeling Resources for Human Prescription Drugs for Industry

https://www.fda.gov/drugs/laws-acts-and-rules/fdas-labeling-resources-human-prescription-drugs

https://www.usp.org/health-quality-safety/labeling

FDA. FD&C Act Provisions that Apply to Human Drug Compounding. 

. Aug. 13, 2021. (accessed Nov. 1, 2024).

Abdus-Samad, Jibril. FDA Drug Product Nomenclature. FDA.gov. Dec. 4, 2019.

https://www.fda.gov/media/134015/download

Calculating the amount of drug needed for compounding requires different considerations for respective drug types and forms.