USP <795> Guidelines
United States Pharmacopeia (USP) Chapter <795> provides standards for compounding quality nonsterile preparations to help ensure patient benefit and reduce risks such as contamination, infection, or incorrect dosing. As of 2020, the 2008 revision is currently official. Non-sterile compounding must occur in a separate space from sterile compounding.
USP <797> Guidelines
USP <797> provides minimum practice and quality standards for CSPs of drugs and nutrients, based on the current scientific information and best sterile compounding compliance practices at the time of revision. USP pertains to the compounding of both hazardous and nonhazardous drugs. As of 2020, the 2014 revision is currently official.
For full allowable beyond use dating (BUD,) the currently enforceable chapter requires an ISO Class 5 PEC (“hood”) in an ISO Class 7 buffer area (“cleanrooms”) accessible via an ISO Class 7 or 8 ante-area. The ante-area minimum classification is defined by the differential pressure between the buffer area and the ante area: ISO Class 8 for a positive pressure buffer area used only for non-hazardous compounding, or ISO Class 7 for a negative pressure buffer area which allows hazardous compounding.
|
USP Requirement |
ISO Class Number |
Maximum Concentration Limit |
FED STD 209e |
||
|
FED STD 209e |
Particles ≥0.5 μm /ft3 of air |
||||
|
PEC |
PEC |
352 |
100 |
Class 100 |
|
|
Not Applicable |
ISO 6 |
3,520 |
1,000 |
Class 1,000 |
|
|
SEC |
ISO 7 |
35,200 |
10,000 |
Class 10,000 |
|
|
Anteroom for positive pressure SEC only |
ISO 8 |
352,000 |
100,000 |
Class 100,000 |
ISO 14644-1 also defines temperature and humidity ranges (16°C - 19°C, 55% - 65%.) USP <797>, 2014 does not apply these ranges and rather states that facilities typically include “a temperature of 20°C or cooler”1 without reference to compounding area humidity.
Though not currently enforceable, the most recent revision of USP <797> recommends “the cleanroom suite should be maintained at a temperature of 20°C or cooler and a relative humidity below 60%.“2 USP commentary responses have stated that “the chapter recommends a temperature of 20°C or lower and a relative humidity below 60%”3 but do not require it. While maintaining the cleanroom within those parameters is safe, if it is not reasonable for that facility, “facilities must determine the appropriate temperature and relative humidity for the compounding area, which can be verified through microbial air and surface sampling.”3
1 USP 797 2014
2 USP 797 2019
3 USP 797 Commentary 2019
USP <800> Guidelines
USP <800> describes hazardous drug handling related to the receipt, storage, compounding, dispensing, administration, and disposal of both sterile and nonsterile 15 products and preparations. As of 2020, USP <800> is official but informational only, some states are enforcing parts of the chapter.
Hazardous cleanroom suites must include a negative pressure ISO Class 7 buffer room and a positive pressure ISO Class 7 ante-room. Hazardous compounding, preparation, and storage areas must be externally vented.
USP Guideline Enforcement
USP Chapters <1> - <999> are enforceable in the United States by the Food and Drug Administration (FDA) per section 503A(b)(1)(B) of the FD&C Act.
ISO 14544-1 Cleanrooms Classifications
ISO 14544-1 is not enforceable by section 503A. USP Chapter <797>, 2014 adapts ISO 14644-1:1999 to define compounding cleanrooms air quality. The chapter also defines air quality by Federal Standard 209e. 209e was officially cancelled in 2001 but the FE “class” terminology is sometimes still used. Compounding cleanrooms air quality is defined using ISO Class terminology by limits in particle of 0.5 μm and larger per cubic meter and does not require or allow certification based on other particle sizes defined by ISO 14544-1.
cGMP 503B Compounding and Manufacturing Cleanrooms
Drug manufacturers and compounding pharmacies which distribute products to hospitals, pharmacies, and other healthcare providers without a prescription are regulated by the FDA and subject to cGMP standards.
At Grifols, we design, engineer, and operate our own manufacturing facilities while serving as a contract manufacturer for other mid-size, large, and generic pharmaceutical and medical device companies. We operate FDA-Registered manufacturing establishments in California, North Carolina, and Spain. Our expertise is rooted in over 75 years of vertically-integrated experience producing high-quality intravenous and other parenteral solutions, diluents, clinical nutrition, and medical devices for the healthcare industry. We have designed and built more than 2 million ft2 of cGMP cleanrooms worldwide.
We make this expertise available to clients seeking design and build or renovation of spaces to achieve their own cGMP sterile compounding or manufacturing needs. Please request a rep to discuss your unique goals and circumstances.
Testing & Certification
Cleanrooms certification services include particle count, HEPA filter integrity, HEPA filter velocity and volume. Last invoice is held until the cleanrooms passes Controlled Environment Testing (CETA) certification by an impartial third-party.
Learn more about inclusiv Modular Cleanrooms
Modular Cleanrooms Specifications
Promote safety and compliance in the design, construction, and environmental.
Construction Process
We accompany you throughout the process until the final certification.
Case Study: USP Compliance Cleanrooms
Cleanrooms Renovation for USP <797> and USP <800> Compliance