General Chapters: <797> PHARMACEUTICAL COMPOUNDING-STERILE PREPARATIONS -

APPENDIX

CRITERIA	LOW-RISK LEVEL		MEDIUM-RISK LEVEL		HIGH-RISK LEVEL
Compounding Conditions	Compounded entirely under ISO Class 5 (Class 100) conditions Compounding involves only transfer, measuring, and mixing manipulations with closed or sealed packaging systems that are performed promptly and attentively Manipulations are limited to aseptically opening ampuls, penetrating sterile stoppers on vials with sterile needles and syringes and transferring sterile liquids in sterile syringes to sterile administration devices and packages of other sterile products		All conditions listed under low-risk level Multiple individual or small doses of sterile products are combined or pooled to prepare a CSP that will be administered either to multiple patients or to one patient on multiple conditions Compounding process includes complex aseptic manipulations other than the single-volume transfer Compounding process requires unusually long duration The sterile CSPs do not contain broad-spectrum bacteriostatic agents, and are administered over several days		Nonsterile ingredients are incorporated or a nonsterile device is employed before terminal sterilization Sterile ingredients, components, devices and mixtures are exposed to air quality inferior to ISO Class 5 (Class 100) Nonsterile preparations are exposed for not more than 6 hours before being sterilized Nonsterile preparations are terminally sterilized but are not tested for bacterial endotoxins It is assumed that the chemical purity and content strength of ingredients meet their original or compendial specifications in unopened or in opened packages of bulk ingredients
QA Program	Formalized in writing Describes specific monitoring and evaluation activities Reporting and evaluation of results Identification of follow-up activities when thresholds are exceeded Delineation of individual responsibilities for each aspect of the program		See low-risk level.		See low-risk level.
QA Practices	Routine disinfection and quality testing of direct compounding environment Visual confirmation of personnel processes regarding gowning, etc. Review of orders and packages of ingredients to assure correct identity and amounts of ingredients Visual inspection of CSP Media-fill test procedure performed at least annually for each person		See low-risk level.		See low-risk level.
Outcome Monitoring	Yes		Yes		Yes
Reports/Documents	Written policies and procedures Adverse event reporting Complaint procedures Periodic review of quality control documents		See low-risk level.		See low-risk level.
Patient and Caregiver Training	Formalized program that includes Understanding of the therapy provided Handling and storage of the CSP Appropriate administration techniques Use and maintenance of any infusion device involved Use of printed material Appropriate follow-up		See low-risk level.		See low-risk level.
Maintaining Product Quality and Control once the CSP leaves the Pharmacy (both institutional based and NICPs)	Packaging, handling, and transport Written policies and procedures including the packaging, handling, and transport of chemotoxic/hazardous CSPs Use and storage Written policies and procedures Administration Written policies and procedures dealing with such issues as handwashing, aseptic technique, site care, etc. Education/Training Written policies and procedures dealing with proper education of patients and caregivers ensuring all of the above		See low-risk level.		See low-risk level.
Storage and Beyond-Use Dating	Specific labeling requirements Specific beyond-use dating policies, procedures, and requirements Policies regarding storage		See low-risk level.		See low-risk level.
Storage Conditions and Beyond-Use Dating for completed CSP	In the absence of sterility testing, storage periods (before administration) shall not exceed the following:
	Room temperature 2–8 –20	48 hours 14 days 45 days	Room temperature 2–8 –20	30 hours 7 days 45 days	Room temperature 2–8 –20	24 hours 3 days 45 days
Finished Product-Release Checks and Tests	Written policies and procedures that address Physical inspections Compounding accuracy checks		See low-risk level.		See low-risk level.
Finished Product-Release Checks and Tests	Written policies and procedures that address Sterility testing Pyrogen testing Potency testing		See low-risk level.		See low-risk level.
CSP Work Environment	Appropriate solid surfaces Limited (but necessary) furniture, fixtures, etc. Anteroom area Buffer zone		See low-risk level.		See low-risk level.
Equipment	Written policies and procedures that address calibration, routine maintenance, personnel training		See low-risk level.		See low-risk level.
Components	Written policies and procedures that address Sterile components		See low-risk level.		Sterile and nonsterile drug components must meet the compendial standards if available Written policies and procedures that address Sterile components Nonsterile components
Processing: Aseptic Technique	Written policies and procedures that address specific training and performance evaluation Critical operations are carried out in a Direct Compounding Common Area (DCCA)		See low-risk level.		See low-risk level.
Environmental Control	Policies and procedures that address Cleaning and sanitizing the workspaces (DCCA) Personnel and gowning Standard operating procedures		See low-risk level.		See low-risk level.
Verification Procedures Sterility Testing	Not required		Not required		Yes, recommended
Verification Procedures Environmental Monitoring	Certification of LAFW and barrier isolates every six (6) months Certification of the buffer room/zone and anteroom/zone every six (6) months Bacterial monitoring using an appropriate manner at least monthly		See low-risk level.		See low-risk level.
Verification Procedures Personnel Training and Education	Initially and annually thereafter Didactic review Written testing Media-fill testing		See low-risk level.		See low-risk level.


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