The new revision provides standards to protect personnel and the environment when handling hazardous drugs (HDs). In a recent webinar, Baker’s Science Director Kara Held and Engineering Test Supervisor Aaron Johnson provided an overview of the expected changes involving primary and secondary engineering controls (e.g., biological safety cabinets, clean rooms, etc.). We received some great questions from attendees and are providing the below summary for the benefit of all who are preparing to implement the proposed guidelines over the coming months.
For reference, you may download a copy of the proposed chapter here.
The USP Pharmacopeial Forum will be accepting comments on the proposed USP <800> chapter until May 31, 2015. At that time, a decision will be made as to the date of publication, and enforcement and inspections will begin on the principles adopted.
The FDA is the enforcement arm of the USP guidelines and will most likely be involved at the compounding level now. As this review and framework is worked out, they will inspect and qualify facilities if they apply for statuses like 503B.
The way the situation is proceeding at this time, it is likely that all facilities will need to comply, although the timeframe to accomplish this is yet to be determined.
A primary engineering control like a biosafety cabinet may be placed in an unclassified Containment Segregated Compounding Area (C-SCA) rather than a clean room environment with the stipulation that the work involves low-risk level compounding sterile preperations with a Beyond Use Date of 12 hours or less.
In the proposed USP <800> chapter, C-STDs and medical surveillance are recommendations only. C-STDs offer additional levels of user protection during hazardous drug compounding and administering practices. Medical surveillance is designed to minimize the adverse effects in personnel potentially exposed to HDs and should be part of the standard operating procedure.
See line 119 of the proposed chapter. HDs must be stored in a negative pressure room that has at least 12 air changes per hour (ACPH). Line 134 states that refrigerated antineoplastic HDs must be stored in a dedicated refrigerator in a negative pressure area with at least 12 ACPH (e.g., a storage room, buffer room, or C-SCA). There is no requirement for a negative pressure refrigerator.
No, this is not a requirement. For compounding sterile HDs, a Class II or Class III biosafety cabinet, or CACI, may be used in a C-SCA as long as they are externally vented. Only low-volume compounding sterile preparations can be performed the Beyond Use Date shall not exceed 12 hours, according to USP <797>.
This is correct. All primary engineering controls used for HD compounding must be placed in a negative pressure room with at least 12 ACPH. The room must be under negative pressure of 0.01-0.03″ W.C. The current allowance in USP <797> of an isolator outside of a non-negative pressure room will be eliminated.
Yes. See beginning on line 179 of the proposed chapter. Non-sterile products can be prepared in a Class I or Class II biosafety cabinet or containment ventilated enclosure (CVE) located in a negative pressure room, as long as the BSC or CVE is externally vented or double HEPA filter exhausted. For a Class II Type A2 cabinet, a properly functioning canopy exhaust connection must be used according to NSF/ANSI Standard 49.
As a synthetic steroidal compound, a primary engineering control will probably be required for the preparation of Megace and any other compounds deemed hazardous to handle.
If this room is an ISO Class 7 buffer area, then the adjacent room must be at least ISO Class 7. If you are talking about a C-SCA, then the single pass door is acceptable so long as the C-SCA meets the negative pressure and ACPH requirements. Also, the Beyond Use Date for segregated compounding areas referenced in USP 797 must be followed.
Our understanding is that if a facility creates compounded chemicals on-site, following USP <800> will be a requirement and that facility will be under the purview of the FDA.
This relates to sterile aqueous solutions rather than solid dose formulations due to how these doses differ in patient administering. See line 60 of the proposed chapter.
This is likely a prudent step. Air changes are only as good as the air being changed. Testing for contaminants is never a bad idea. Change equipment (HVAC, filters, exchange grates) must be tested for growth and moisture. Otherwise, a contaminated system could cause issues. The rooms should also be monitored for contamination by a designed interval testing system.
Not at this time.
Yes, if they are coming into the United States. Harmonization of regulations may indirectly impact them.