Standards, Oversight, and Pharmacy Technician Responsibilities in Nonsterile Compounding
Activity Level: 1-hour freeCE Live Webinar.
Educational Purpose: Nonsterile compounding is an essential pharmacy practice component requiring adherence to standards and regulations to ensure patient safety and quality preparation. The course introduces oversight organizations and examines how standards, regulations, and accreditation influence daily practice, with a focus on pharmacy technician responsibilities.
Learning Objectives:
Identify the roles of regulatory, standards-setting, and accreditation bodies involved in nonsterile compounding practice.
Define key terms associated with nonsterile compounding regulations, standards, and guidelines.
Describe the roles and responsibilities of pharmacy technicians in supporting compliant and high-quality nonsterile compounding processes.
Defining Pharmaceutical Compounding
Core Definition: The process of combining, mixing, or altering ingredients to create a medication that meets the individual needs of a patient based on a prescription.
FDA Status: Compounded medications are not evaluated by the FDA for safety, efficacy, or quality prior to dispensing.
Prohibition on Copies: Compounded medications cannot be a copy of a commercially available medication.
General Classifications:
Nonsterile vs. Sterile compounding.
Hazardous vs. Nonhazardous compounding.
Nonsterile Compounding Specific Definition (USP <795>): "Combining, admixing, diluting, pooling, reconstituting other than as provided in the manufacturer’s labeling, or otherwise altering a drug product or bulk drug substance to create a nonsterile preparation."
Manufacturing vs. Compounding:
Manufacturing: Involves the production, preparation, propagation, conversion, and processing of a drug or device through extraction or synthesis. It includes packaging/repackaging, labeling/relabeling, and the promotion/marketing of drugs and devices.
Compounding: Focuses on professional practice for individual patients.
Reasons to Compound:
Adjust the strength of a commercially available product.
Flavor or sweeten a product to improve pediatric or patient adherence.
Prepare a different dosage form (e.g., liquid for a patient who cannot swallow pills) than what is commercially available.
Prepare a dosage form without specific ingredients (e.g., removing dyes or allergens).
Prepare medications currently under drug shortage or recall.
Reasons to NOT Compound:
Compounding drugs prior to receiving a valid prescription (except for small-scale anticipatory compounding).
Compounding drugs removed from the market by the FDA for safety reasons.
Compounding drugs that are essentially copies of commercially available products.
Legal and Regulatory Context of Compounding
Historical Foundation: The 1938 Federal Food, Drug, and Cosmetic Act (FDCA) authorized the FDA to oversee pharmaceutical manufacturing, requiring drugs to be approved based on safety and preventing false or misleading labeling.
1997 Food and Drug Administration Modernization Act (FDAMA):
Exempted pharmacies from FDCA regulations if they refrain from advertising specific products and follow requirements to increase drug safety.
Ensures patient access to individualized therapy.
Prevents unnecessary FDA regulation of professional health practice.
Section 503A Alignment: Compounders must use bulk drug substances and ingredients complying with USP-NF monographs (if available) and the USP chapter on pharmacy compounding.
2013 Compounding Quality Act (Drug Quality and Security Act):
Defined two distinct categories of compounding pharmacies: 503A and 503B.
Set federal and state oversight authority.
503A Traditional Compounding Pharmacies
Definition: Traditional compounding pharmacies regulated primarily by State Boards of Pharmacy.
Who can compound: Licensed pharmacists in licensed pharmacies or federal facilities, or licensed physicians.
Requirements:
Must be in response to a valid prescription for an individual patient.
Anticipatory Compounding: Allowed only if the patient has a history of valid prescriptions and an established relationship with the pharmacy.
Limitations: Cannot make copies of commercial medications; cannot compound for in-office use.
Interstate Commerce: May distribute up to 5% of total prescription orders interstate unless the state has signed a memorandum of understanding (MOU) with the FDA allowing for greater distribution.
Substance Requirements: Must have a USP-NF monograph, be components of an FDA-approved drug, or be on the FDA-approved list of bulk drug substances.
Exclusions: Cannot be on the FDA list of drugs that are difficult to compound OR the list of drugs withdrawn from the market for being unsafe/ineffective.
Oversight: No registration or reporting requirements from the FDA, but must adhere to USP standards and State Board of Pharmacy regulations.
503B Outsourcing Facilities
Definition: Facilities that can compound larger quantities with or without patient-specific prescriptions.
Who can compound: Under the direct supervision of a licensed pharmacist.
Capabilities: Can perform sterile compounding; can sell to healthcare facilities or for office stock; can sell preparations in interstate commerce.
Limitations: Cannot make copies of commercially available drugs; cannot prepare drugs withdrawn from the market or those that present extreme difficulty to compound.
Drug Substance Requirements:
Comply with USP-NF monographs.
Be on a 503B-specific list of bulk drug substances or an FDA-approved drug list.
Appear on a drug shortage list at the time of compounding.
Must have a valid Certificate of Analysis (CoA).
Must be manufactured by an establishment registered with the FDA.
Regulatory mandates: Mandatory FDA registration and payment of applicable fees; must submit reports identifying all drugs compounded; must submit adverse event reports; must comply with current Good Manufacturing Practices (cGMP) and USP <795>; subject to FDA inspections.
United States Pharmacopeia (USP) and Chapter <795>
The USP: An independent, scientific, non-profit organization providing definitions and requirements for pharmaceutical settings.
USP-NF: Contains standards for medicines, dosage forms, drug substances, excipients, and compounded preparations.
Enforceability: Chapters numbered below 1000 (<1> to <999>) are considered enforceable standards.
USP <795> Overview:
Title: Pharmaceutical Compounding—Nonsterile Preparations.
Version: Most recent version effective November 1, 2023.
Function: Establishes MINIMUM practices and quality standards for compounded nonsterile preparations (CNSPs) for humans and animals.
Verbatim Terms:
"Must": Indicates a requirement.
"Should" and "May": Indicate recommendations.
Goals of <795>: To minimize harm and death resulting from:
Excessive microbial contamination.
Variability from intended strength (e.g., exceeding of labeled strength).
Physical and chemical incompatibilities.
Chemical and physical contaminants.
Use of inappropriate quality ingredients.
Scope of Preparations: Solid oral, liquid oral, rectal, vaginal, topical, nasal/sinus, and otic preparations.
Not Covered: Nonsterile radiopharmaceuticals (<825>), simple reconstitution, repackaging, splitting tablets, or administration.
Applicability: Applies to all persons (pharmacists, technicians, nurses, physicians, etc.) and all places (pharmacies, hospitals, healthcare institutions) where CNSPs are prepared.
Enforcement: Left to state boards of pharmacy; states may require more stringent environmental controls and quality procedures.
USP Chapter <800>: Hazardous Drugs
Title: Hazardous Drugs—Handling in Healthcare Settings.
Context: Relevant for handling hazardous nonsterile preparations.
Scope: Practice and quality standards for handling hazardous drugs (HDs) to promote patient, worker, and environmental safety.
Processes Covered: Receipt, storage, compounding, dispensing, administration, and disposal of both sterile and nonsterile HD products.
Application: Applies to all healthcare personnel and entities that store, prepare, transport, or administer HDs.
Key Terminology in Compounding
Certificate of Analysis (CoA): A report from the supplier of a component, container, or closure containing specifications, results of all analyses, and a description of the material.
Component: Any ingredient used in compounding, including active ingredients, added substances (excipients), or conventionally manufactured products.
Designated Person: The individual responsible for the performance, operations, and personnel involved in CNSP preparation. Responsibilities include training, implementing USP <795>, oversight of SOPs, QA/QC program management, BUD assignment, and documentation.
Assigned Trainer: One or more individuals assigned by the designated person to be responsible for directly providing training, observation, and evaluation of personnel preparing CNSPs.
Oversight: The review, monitoring, and supervision of actions taken by personnel; the oversight figure is responsible for actions and must be available for consultation.
Beyond-Use Date (BUD): The date (or date and hour) after which a CNSP must not be used, stored, or transported. It is calculated in hours, days, or months from the time of compounding.
BUD vs. Expiration Date:
BUD: Specifically for the compounded preparation based on the date of compounding.
Expiration Date: Identifies the time a conventionally manufactured product, API, or excipient is expected to meet compendial requirements or maintain quality under specific storage conditions.
Quality Systems and Safety Data Sheets
Standard Operating Procedure (SOP): Living documents providing written instructions for specific steps to follow in all activities. All personnel must be trained on and follow these.
Safety Data Sheet (SDS): A detailed informational document listing safety-related information (Occupational, Physical, Health, Environmental). Key sections include:
Section 1: Identification (Product identifier, manufacturer info, use restrictions).
Section 2: Hazard(s) identification.
Section 3: Composition/information on ingredients.
Section 4: First-aid measures (Immediate/delayed symptoms and treatment).
Section 5: Fire-fighting measures.
Section 6: Accidental release measures (cleanup, PPE, and containment).
Section 7: Handling and storage (including incompatibilities).
Section 8: Exposure controls/Personal protection (PELs, TLVs, engineering controls, PPE).
Section 9: Physical and chemical properties.
Section 10: Stability and reactivity.
Section 11: Toxicological information (routes of exposure, symptoms, toxicity measures).
Quality Assurance (QA): A system of procedures and oversight ensuring the process consistently meets quality standards. Programs must be established in SOPs and reviewed at least once every 12 months.
Quality Control (QC): The sampling, testing, and documentation of results to ensure specifications are met before a CNSP is released. Programs must be reviewed every 12 months.
Fast Track Program: Facilitates expedited development and review of new drugs/biologics intended to treat serious conditions or address unmet medical needs.
Organizational Oversight and Accreditation
State Boards of Pharmacy: Primary authority regulating compounding, registering/licensing technicians, and handling complaints/disciplinary actions. They set state-specific policies for record-keeping and labeling.
FDA: Oversees ingredient integrity, prescription labeling, and promotion. Has authority over outsourcing facilities (503B).
FTC: Oversees commercial advertising fairness.
DEA: Oversees controlled substances used in compounds.
Pharmacy Compounding Accreditation Board (PCAB):
A service of ACHC established in 2007.
Provides voluntary accreditation based on USP guidelines.
Evaluates compliance through extensive SOP reviews and onsite surveys.
Mission: To serve the public good by identifying pharmacies meeting accreditation criteria and promoting compounding quality and safety.
Compounding Organizations: Professional Compounding Centers of America (PCCA) and Alliance for Pharmacy Compounding (APC) provide guidance and education.
Role of the Pharmacy Technician
Scope of Practice: Compounding is considered an advanced role. Technicians use science, math, and technology skills to support compound safety.
Tasks NOT Allowed for Technicians:
Final verification of the compounded product.
Clinical decision-making.
Prescription interpretation.
Training and Evaluation: Personnel must be qualified before working independently. Core competencies include:
Hand hygiene and garbing.
Cleaning and sanitizing.
Handling/transporting components.
Measuring and mixing.
Equipment use and calibration.
Documentation and interpreting SDS/CoA.
The Triad: A collaborative relationship between the Patient, Pharmacist, and Physician to determine optimal therapy.
Compounding Errors and Prevention
Types of Errors:
General Errors: Procedural failures or human error.
Incorrect Ingredients: Using the wrong API or excipient.
Incorrect Concentrations: Calculation or measurement mistakes regarding strength/ratios.
Incorrect Equipment Use: Improper selection or calibration.
Microbial Contamination: Introduction of organisms via poor hygiene or cleaning.
Analytical Testing Issues: Problems with confirmation of identity or concentration.
Causes and Prevention Strategies:
Cause: Lack of education and training. Prevention: Structured onboarding, competency assessments, and continuing education.
Cause: Lack of implemented SOPs. Prevention: Detailed SOP development and regular review.
Cause: Improper use of equipment. Prevention: Routine maintenance/calibration and equipment training.
Cause: Calculation errors. Prevention: Double-checking, standardized worksheets, and independent verification.
Cause: Misinterpretation of orders. Prevention: Clarification with prescribers/pharmacists and verify against Master Formulation Records.
Questions & Discussion
Regulatory Reflection: How do regulatory standards such as USP <795> and oversight from state boards of pharmacy and the FDA contribute to patient safety, and what are the risks if these standards are not followed?
Safety/Quality Reflection: In what ways can pharmacy technicians support quality and safety in the nonsterile compounding process, and how can proper training and adherence to SOPs reduce compounding errors?