The past decade has brought dramatic and necessary change to the outsourced sterile compounding industry, or 503B facilities.
Historically, hospitals and health care systems compounded drugs in house but the practice of outsourcing these services has grown rapidly. Since the tragic New England Compounding Center (NECC ) tragedy in 2012, sweeping new guideline have been put into place that provide for more oversight and require outsourcing companies adhere to more stringent safety regulations.
The Drug Quality and Security Act (DQSA) was signed into law on November 27, 2013. The act identified 503B “Outsourcing Facilities” and stated they must comply with the following requirements:
- Voluntary registration with the FDA
- Compound of sterile drugs
- Is not required to obtain a patient-specific prescription prior to compounding
- If not a licensed pharmacy, all compounding must be done under the supervision of a licensed pharmacist subject to state licensing laws
- Must comply with cGMP (current good manufacturing process) requirements and subject to FDA inspections
- Must report which products they are compounding and any adverse events
- Must pay establishment, annual fees, and reinspection fee if applicable
This important regulatory elevation has changed the way the entire segment must operate. 503B compounding facilities must migrate from the previous guidance offered by USP <797> to cGMP regulations.
The chart below shows the stark difference between the two regulations.
|Key Components/Sections||< USP 797 >||cGMP|
|Workflow||Not specified||Unidirectional flow of personnel and materials|
|Production||Can allow multiple products simultaneously in a cleanroom||Defined areas for production with line clearances|
|Beyond-Use-Date (BUD)/ Expiration Date, Stability, and Endotoxin testing||Only for high-risk or Extended BUD||Required for all products; Stability testing data used to establish expiration dating|
|Final Container Sterility/Potency/Stability Testing and Reserve Samples||Not required||Required for every batch created|
|Material Testing||Not required||Required|
|Quality Control (QC) Quarantine, Release Testing, and Storage||Not required||Required prior to release|
|Environmental Control||Daily temperature monitoring||Continuous temperature, pressure, and humidity, with monitoring|
|Environmental Monitoring||Air: 6 months|
Surface: periodically (>6 months)
Personnel: 1-2 times/year
Personnel: daily (with monitoring during production)
|Sterile Garbing||Sterile gloves||FULL Sterile garb|
|Sterile Disinfectants||Isopropyl alcohol||Rotation of disinfectants, & sporicidal agents; including validation|
|Equipment, Process, IT System, and Cleaning Validation||Not required||Required|
|Documentation (GDP)||As required per prescription and by state||Required for all batches, testing, processes and validation.|
|Change Control (Process, Equipment, Material, and Document)||Not required||Required|
|Adverse Drug Event (ADE) Reporting with Root Cause Analysis, investigation, and CAPA||Not required||Required|