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Transcript of Pharmaceutical Compounding – Sterile and Nonsterile ... · PDF filestandards for...
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Pharmaceutical Compounding – Sterile and Nonsterile Preparations
Jeanne Sun, PharmD
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Agenda
• Legal Framework
• Overview – <795> Pharmaceutical Compounding – Nonsterile Preparations – <797> Pharmaceutical Compounding – Sterile Preparations
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Legal Recognition In The US
• USP's standards for medicines, dietary supplements and foods are recognized in varying capacities in a variety of U.S. legislation. – 1938 Federal Food, Drug and Cosmetic Act (FDCA) recognized
USP & NF standards for strength, quality, purity, packaging, and labeling
• 1997 Food Drug Administration Modernization Act first recognized standards for compounding requiring USP-NF monograph standards for drug substances and ingredients and USP’s chapter on compounding
• 2013 Drug Quality and Security Act amended the FDCA reaffirmed USP’s role in compounding and granted the FDA more authority to regulate and monitor the manufacturing of compounded drugs
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Regulatory Oversight
• Two Regulatory Bodies
– States • Boards of Pharmacy
– Federal Government
• Food and Drug Administration (FDA)
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Compounding in the Law
There are 3 types of standards for compounding: 1. Monographs for ingredients
used in compounded preparations – Drug Substance Monographs
2. Monographs for compounded preparations – Compounded Preparation
Monographs 3. Practice standards
– General Chapters
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Compounding General Chapters
• <795> Pharmaceutical Compounding – Nonsterile Preparations
• <797> Pharmaceutical Compounding – Sterile Preparations • <800> Hazardous Drugs – Handling in Healthcare Settings • <1163> Quality Assurance in Pharmaceutical Compounding • <1160> Pharmaceutical Calculations in Pharmacy Practice • <1176> Prescription Balances and Volumetric Apparatus
Used in Compounding
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<795> Pharmaceutical Compounding – Nonsterile Preparations
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<795> Overview
• Purpose – To provide guidance on applying good compounding practices
for nonsterile formulations for humans or animals. – To provide general information to enhance the compounder's
ability to extemporaneously compound preparations that are of acceptable strength, quality, and purity.
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<795> Overview
Categories Facilities
Component Selection, Handling, & Storage
Stability & Beyond-Use Dating
Documentation Animal Patients
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<795> Categories
• Criteria to determine classification
– Degree of difficulty or complexity of the compounding process
– Stability information and warnings – Packaging and storage
requirements – Dosage forms – Complexity of calculations – Local versus systemic biological
disposition – Level of risk to the compounder – Potential for risk of harm to the
patient
Complex
Moderate
Simple
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<795> Facilities
• Adequate space for compounding
• Temperature and humidity monitoring for storage
• Potable Water – For hand and equipment washing – Air-dryer or single-use towels
• Purified Water
– Shall be used for compounding – Should be used for rinsing
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<795> Component Selection, Handling, & Storage
• Recommended: – USP, NF, or FCC substance – Manufactured in an FDA-registered facility
• For human use
– Consult FDA list of components withdrawn or removed from the market for safety or efficacy reasons1
• For food-producing animals
– Consult FDA list of components prohibited for use2
1. See http://www.fda.gov/ohrms/dockets/98fr/100898b.txt 2. See http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=530.41
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<797> Stability & Beyond-Use Dating (BUD)
• The BUD is not later than the time remaining until the earliest expiration date of any API or 6 months, whichever is earlier when stored at controlled room temperature
For Nonaqueous Formulations
• The BUD is not later than 14 days when stored at controlled cold temperature
For Water-Containing Oral Formulations
• The BUD is not later than 30 days when stored at controlled room temperature
For Water-Containing Topical/Dermal and Mucosal Liquid and Semisolid Formulations
In the absence of stability information to a specific preparation, the maximum BUD recommended:
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<797> Documentation
Master Formulation Record • Name, strength, and dosage form • Calculations & Verifications • Ingredients & Quantities • Compatibility & Stability Information • Equipment • Mixing instructions • Example labeling • Assigned BUD • Storage conditions • Packaging and storage requirements • Description of final preparation
Compounding Record • Name, strength, and dosage • Master Formulation Record reference • Names & quantities of all components • Source, lot no., & expiration dates of
components • Total quantity compounded • Compounder identifier and date • Assigned BUD • Duplicate label • Description of final preparation • Issues or any adverse reactions
Documentation enables a compounder to systematically trace, evaluate, and replicate the steps throughout the preparation process
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<797> Animal Patients
• Nature of the animal patient shall be determined – Companion Animals – Performance Animals
• Strictly regulated by federal and state governments – Food-Producing Animals
• Accurate length of time to withhold treated animal tissues from the human food supply.
• Withdrawal time (WDT) must be included on the dispensing label • Ingredients cannot be on FDA list of prohibited components1
1. See https://www.fda.gov/animalveterinary/resourcesforyou/ucm380135.htm
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<797> Pharmaceutical Compounding – Sterile Preparations
Last revised USP31-NF26 2S
Currently under revision
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<797> Overview
• Purpose: – To provide quality standards for compounded sterile preparations – To describe conditions and procedures to prevent harm,
including death, to patients that could result from • microbial contamination (nonsterility) • excessive bacterial endotoxins • variability in the intended strength • unintended chemical and physical contaminants • ingredients of inappropriate quality
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<797> Overview
CSP Risk Levels Facilities
Personnel Monitoring
Environmental Monitoring
Finished Preparations Monitoring
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<797> CSP Risk Levels
• Assigned based on – Maintenance of sterility vs. achievement of sterility – Complexity of preparation – Stability of the components – Temperature at which stored
Low Risk Level CSPs
Low-Risk Level CSPs with 12-Hour or Less BUD
Medium-Risk Level CSPs
High-Risk Level CSPs
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<797> CSP Risk Levels
Low-Risk with 12
hour
• 12 hours
• 12 hours
• N/A
Low-Risk Level CSPs
• 48 hours
• 14 days
• 45 days
Medium-Risk Level
CSPs
• 30 hours
• 9 days
• 45 days
High-Risk Level CSPs
• 24 hours
• 3 days
• 45 days
Controlled Room Temperature (20° to 25° C)
Cold Temperature (2° to 8° C)
Solid Frozen State (-25° to -10° C)
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<797> Facilities
• ISO Class 5 PEC • Unclassified Space
Segregated Compounding
Area
• ISO Class 5 PEC • Buffer Room • Ante Room
Cleanroom Suite
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<797> Personnel Monitoring
Gloved Fingertip Sampling • Evaluates hand hygiene and garbing competency
Aseptic Media Fill Testing • Stimulates conditions encountered during compounding
to evaluate aseptic manipulations
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<797> Environmental Monitoring
Certification • Monitors primary and secondary engineering controls
Viable Air Monitoring • Monitors environmental microbial growth
Surface Sampling • Evaluates cleaning and disinfecting procedures and work
practices
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<797> Finished Preparations Monitoring
Physical Inspection • Inspect for visible particles or foreign matter
Labeling and Accuracy Checks • Verify ingredients and volumes
Sterility and Endotoxin Testing • Testing for potential contamination
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