Pharmaceutical Compounding Sterile and Nonsterile Preparations. Jeanne Sun, PharmD

Transcription

1 Pharmaceutical Compounding Sterile and Nonsterile Preparations Jeanne Sun, PharmD

2 Agenda Legal Framework Overview <795> Pharmaceutical Compounding Nonsterile Preparations <797> Pharmaceutical Compounding Sterile Preparations

3 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 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

4 Regulatory Oversight Two Regulatory Bodies States Boards of Pharmacy Federal Government Food and Drug Administration (FDA)

5 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

6 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

7 <795> Pharmaceutical Compounding Nonsterile Preparations

8 <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.

9 <795> Overview Categories Facilities Component Selection, Handling, & Storage Stability & Beyond- Use Dating Documentation Animal Patients

10 <795> Categories Moderate Simple Complex 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

11 <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

12 1. See 2. See <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 reasons 1 For food-producing animals Consult FDA list of components prohibited for use 2

13 <797> Stability & Beyond-Use Dating (BUD) In the absence of stability information to a specific preparation, the maximum BUD recommended: For Nonaqueous Formulations 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 Water-Containing Oral Formulations The BUD is not later than 14 days when stored at controlled cold temperature For Water-Containing Topical/Dermal and Mucosal Liquid and Semisolid Formulations The BUD is not later than 30 days when stored at controlled room temperature

14 <797> Documentation Documentation enables a compounder to systematically trace, evaluate, and replicate the steps throughout the preparation process 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

15 <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 components 1 1. See

16 <797> Pharmaceutical Compounding Sterile Preparations Last revised USP31-NF26 2S Currently under revision

17 <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

18 <797> Overview CSP Risk Levels Facilities Personnel Monitoring Environmental Monitoring Finished Preparations Monitoring

19 <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

20 <797> CSP Risk Levels Low-Risk with 12 hour Low-Risk Level CSPs Medium- Risk Level CSPs High-Risk Level CSPs Controlled Room Temperature (20 to 25 C) 12 hours 48 hours 30 hours 24 hours Cold Temperature (2 to 8 C) 12 hours 14 days 9 days 3 days Solid Frozen State (-25 to -10 C) N/A 45 days 45 days 45 days

21 <797> Facilities Segregated Compounding Area ISO Class 5 PEC Unclassified Space Cleanroom Suite ISO Class 5 PEC Buffer Room Ante Room

22 <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

23 <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

24 <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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