General USP <800> Summary
What is USP?
The purpose of the chapter is to describe practice and quality standards for handling hazardous drugs in healthcare settings and help promote patient safety, worker safety, and environmental protection. The chapter defines processes intended to minimize the exposure to hazardous drugs in healthcare settings.1
Does USP <800> apply to me?
USP General Chapter <800> applies to all healthcare personnel who handle HD preparations and all entities that store, prepare, transport, or administer HDs (e.g., pharmacies, hospitals and other healthcare institutions, patient treatment clinics, physicians' practice facilities, or veterinarians' offices).1
Who will regulate USP <800>?
For pharmacies, it will be up to the state boards of pharmacy and the FDA. For other healthcare entities, it becomes a little cloudy. However, overall, the respective boards for their respective practices (i.e., medicine, nursing, veterinary medicine, etc.) would have most of the jurisdiction.
When will the chapter become official?
The chapter becomes official December 1, 2019, which is the earliest date a regulatory entity could enforce the chapter. As you all know, some states do not yet enforce USP <795> and <797>. It will be up to the individual states and their respective boards of pharmacy to determine when, if, and how they will start to enforce this new standard.
Has USP made any updates to the chapter since it was published?
Yes. An erratum was published on May 26, 2016 to remove the requirement that the C-SEC be externally vented through HEPA filtration. The C-SEC must still be externally vented.”1
Can state laws/rules/regulations supersede federal laws/rules/regulations?
Yes, and vice-versa. Whichever is more stringent must be followed.
Where can we find local, state and federal regulations for hazardous waste?
We recommend contacting a hazardous waste disposal company.
Is leaving the pharmacy for a lunch break considered voluntary interruption?
We feel that leaving for a lunch break would be considered a voluntary interruption.
Facility
Is there a requirement for an emergency shower in the chapter?
Not explicitly, but Section 5.3 of the chapter states, “An eyewash station and/or other emergency or safety precautions that meet applicable laws and regulations must be readily available.”
Are non-sterile facilities required to have an outside company verify the C-SEC and C-PEC for negative pressure as well as air changes? If so, how often?
Certification is not required for non-sterile rooms in the chapter. We would recommend having an outside company certify non-sterile negative-pressure areas every 6 months.
Can multiple C-PECs be used simultaneously in one C-SEC?
Yes, as long as the air changes per hour (ACPH) are met for the room. Note: There are special requirements if you are looking to do non-sterile and sterile HD compounding in the same room and we do not recommend it except in very limited circumstances.
Can an existing clean room be converted into an HD compounding room?
With the proper changes in engineering controls, it may be possible.
What defines the walls of a hazardous drug room?
The design requirements for walls will depend on if you are compounding sterile or non-sterile preparations. Remember, USP <795> and <797> still apply, respectively. For non-sterile, it appears there is much leeway in design, as the only constraints for the room are “surfaces of ceilings, walls, floors, fixtures, shelving, counters, and cabinets in the non-sterile compounding area must be smooth, impervious, free from cracks and crevices, and non-shedding.”
Are we required to decontaminate the C-PEC on days the pharmacy is closed (e.g., weekends)?
This depends on interpretation by the state boards of pharmacy and the FDA. However, when similar issues have arisen (e.g., cleaning protocols for USP <797>), the boards and the FDA have allowed daily requirements to be skipped on days a pharmacy is closed.
In our facility, our compounding area shares a wall with the break room, but the entrance is several rooms away. Do you think the requirement for the hazardous handling areas to be located away from break rooms means just the entrances to the room or do you think they should not share a wall?
Based on our understanding, as long as the compounding area is physically separated by a wall and a door does not connect the two rooms, it can be next to a break room.
As far as facility surfaces being impervious (i.e., no cracks or crevices), what about electronics in the non-sterile HD lab, like laptops, phones, scanners, printers, etc.?
We would recommend that you consider how these items will deactivated, decontaminated, and cleaned. Washable keyboard and mice are available on the market.
If a surface has a caulked seam, will it meet the architectural finish requirements described in the chapter (i.e., “smooth, seamless, and impervious surfaces”)?
If caulked correctly and inspected on a regular basis, yes.
Can sterile and non-sterile HD compounding be completed in the same C-SEC room?
Yes. However, we do not recommend this except in very limited circumstances.
Is environmental quality control a sterile procedure? Is this required for non-sterile?
Environmental quality control, as it relates to contamination of the work environment by HDs, is not required.
Are we required to purchase an additional electronic mortar and pestle for hazardous drug compounding?
Section 13 states “Disposable or clean equipment for compounding (such as mortars and pestles, and spatulas) must be dedicated for use with HDs.” Further, Section 12 states: “HDs that do not require any further manipulation, other than counting or repackaging of final dosage forms, may be prepared for dispensing without any further requirements for containment unless required by the manufacturer or if visual indicators of HD exposure hazards are present (e.g., HD dust or leakage).” Our understanding would be that you would need a separate electronic mortar and pestle because the HD preparation would be undergoing further manipulation by that device which is required to be dedicated to use with HDs.
For non-sterile compounding of HDs, are we required to have our electronic mortar and pestle (EMP) and ointment mill in the C-PEC, or just contained in the C-SEC?
There is no requirement that equipment must be in the C-PEC. We would recommend that you evaluate the risk of exposure that may be created by the use of the equipment for your application and determine if that piece of equipment should be utilized in the C-PEC.
Can the sink and dishwasher be used for both hazardous and non-hazardous drugs?
We would not recommend this and suggest that you have separate dishwashers for your hazards and non-hazardous labs.
C-PEC
Can I use the same C-PEC for both HD and non-HD APIs?
No. The chapter only makes an allowance for using a C-PEC dedicated for sterile HD compounding for non-sterile HD compounding, but the C-PEC must be decontaminated, cleaned, and disinfected before resuming sterile HD compounding. We do not recommend this approach except in very limited circumstances.
If I have two separate C-PECs, one for non-hazardous drugs and one for hazardous drugs, can they both be in the same C-SEC for non-sterile compounding?
No.
Can a sterile HD C-PEC hood and non-HD C-PEC hood be in the same ISO 7 negative-pressure room?
No, assuming the non-HD C-PEC hood is positive pressure.
Venting
What are the requirements for non-sterile venting?
For the C-PEC (or hood), it can either be externally vented or vented back into the C-SEC (or room) via redundant (e.g., double) HEPA filtration. The room must be externally vented; the chapter defines “externally vented” as “exhausted to the outside of the building.”
Does a powder containment hood – not an ISO 5 hood – used for sterile compounding have to be externally vented?
There are various interpretations out there on this issue. While working in the ante-room within a powder hood is technically not sterile manipulation, it still is within a classified space. It can be interpreted that all C-PEC’s related to sterile compounding need to be externally vented. Under Section 5.3.2 Sterile Compounding <800> states that “All C-PECs used for manipulation of sterile HDs must be externally vented” Another interpretation could be that only the ISO 5 needs to be vented outside. We are of the opinion that you should design for the stricter scenario.
Should a non-sterile HD compounding room be vented outside of a building, or can it be vented through a HEPA filter into an adjoining room?
The C-SEC must be externally vented (“exhausted to the outside of the building”).
Does each powder hood need to have a HEPA filter? Or, can the hood’s air go to a dust collector, through a HEPA filter, and then outside the building?
Each C-PEC is required to have at least one HEPA filter. If only a single filter is used, the C-PEC must be vented outside. Additionally, an ISO-5 C-PEC must be filtered and vented outside. Only non-sterile C-PECs can be redundantly filtered and returned to the C-SEC air. We would advise not having the C-PEC vented to a dust collector, through a HEPA filter, and then vented outside. Cleaning the dust collector would be problematic.
Where does air exit a C-SEC?
A negative-pressure C-SEC’s airflow would most commonly exit from the ceiling so that it can be vented to the outside of the building.
Why are there ISO 7 rooms in which there are two different air changes per hour (i.e., 12 and 30)?
The chapter allows, in the same way as the current <797>, for two different types of ISO 7 rooms.
A containment segregated compounding area (C-SCA) is allowed to have 12 ACPH, but only low- or medium-risk sterile compounding can occur in this environment. Furthermore, the beyond use dates for these products are limited to a maximum of 12 hours.
Note: There appears to be conflict here between <800> and the current <797>. USP <800> allows for the compounding of low- and medium-risk sterile compounds in the C-SCA, while the current USP <797> only allows low-risk sterile compounding to occur in the C-SCA. This is likely to be addressed by the revision of USP <797>. If you are licensed by a state that requires compliance with the current USP <797> and does not update to requiring the coming revised version of USP <797> while requiring USP <800> compliance you will need to check with the state to see what they expect for compliance.
Compounding
Does non-sterile compounding need to be done in a glove box or a powder containment hood under negative pressure?
Non-sterile compounding must be performed in a Class I biological safety cabinet (BSC) or a containment ventilated enclosure (CVE) (e.g., a powder containment hood under negative pressure). Glove boxes are not addressed in Section 5.3.1, “Non-sterile Compounding”; however, if the glove box is under negative pressure, making it a CACI, it can be used.
Does the chapter require me to have separate equipment dedicated for HD and non-HD compounding?
Section 13 of the chapter, “Compounding,” states, “Disposable or clean equipment for compounding (such as mortars and pestles, and spatulas) must be dedicated for use with HDs.” Our interpretation of this sentence is yes, you do need separate equipment dedicated for HD compounding, such as hoods, balances, ointment mills, mortars and pestles, capsule machines, etc.
Can both hazardous and non-hazardous drugs be compounded in the same room?
No, unless you treat everything compounded in the room as hazardous. The non-hazardous items compounded in the hazardous C-SEC must be labeled, protected, and bagged as if they were hazardous.
Can I classify all of my APIs as hazardous drugs and just compound everything in a negative pressure area?
While it appears the chapter would allow this, there are a couple things to keep in mind if you want to pursue this idea:
- Depending on how big your lab is, costs for converting the whole lab, and subsequent overhead for heating, ventilation and air conditioning (HVAC), could be more trouble than it is worth.
- Everything you handle would need to comply with all of the requirements for gloves, gowns, shoe covers, etc. Therefore, current costs related to consumables could increase dramatically. Costs for disposal could also be dramatically higher.
- All procedures related to labeling, packaging and transport, as outlined in the chapter, would need to be followed for everything you compound.
- You will need to evaluate the mix of what you compound. What percentage of it is HD vs non-HD and how would this affect workflow.
If my pharmacy is not compounding hazardous drugs, do we need a negative-pressure room or negative-pressure hood/double hepa-filtered hood for non-sterile compounding?
No. However, we recommend that you fully review the NIOSH list to ensure your pharmacy is not compounding anything on the list. Further, we recommend that you have an SOP on reviewing drugs that are new to your facility that they do not qualify as a hazardous drug. We would also recommend that all non-sterile compounding that can generate drug particles occur within a powder containment hood and would advise you to check the laws, regulations, and rules of each state you are licensed it to confirm what is required for compliance.
What will be the new procedure regarding compounding and/or reconstituting commercially available drugs that appear on the NIOSH list?
At the beginning of the chapter, “Box 1: Containment Requirements” states:
Drugs on the NIOSH list that must follow the requirements in this chapter include:
- Any HD API
- Any antineoplastic requiring HD manipulation
Furthermore, it explains that if a facility performs an assessment of risk, then:
- Final dosage forms of compounded HD preparations and manufactured HDs, including antineoplastic drugs that do not require any further manipulation other than counting or repacking, are not required to follow all of the containment procedures in the chapter.
- The facility can determine alternative containment strategies for dosage forms of other HDs, including manipulating (e.g., compounding/reconstituting) manufactured non-antineoplastic HDs.
If a hazardous drug is contained in a cream or solution, does it have to be compounded in a negative-pressure room, or can it be compounded in a general compounding area?
This interpretation can be a bit open-ended. We would expect regulatory bodies to require containment of the process until the compounded medication is in its final dosage form. Only then, can it leave the negative pressure area. We would advise you to check for interpretation with Board(s) of Pharmacy you are licensed with.
Is it up to the pharmacy to decide whether USP <800> applies to opening tacrolimus capsules to produce a suspension?
As an HD the opening of Tacrolimus capsules that would generate HD particles in order to prepare more than a single dose would require the use of the C-PEC. Section 5.1: “A C-PEC is not required if manipulations are limited to handling of final dosage forms (e.g., counting or repackaging of tablets and capsules) that do not produce particles, aerosols, or gasses.” Further, Section 13: “If used, APIs or other powdered HDs must be handled in a C-PEC to protect against occupational exposure, especially during particle-generating activities (such as crushing tablets, opening capsules, and weighing powder).”
What should we do with compounded preparations that contain both hazardous and non-hazardous drugs? Are we able to move the non-HD package into the HD package for this purpose?
If you move a container from your non-sterile non-HD lab to your HD lab, it will have to remain in your HD lab from that time on. Chemicals from the HD lab could not be brought out to be used in your non-HD lab.
Is repackaging a topical preparation from an EMP jar into a syringe or pump considered manipulation?
We would advise you to check with the Board(s) of Pharmacy you are licensed by for interpretation.
Personal Protective Equipment (PPE)
Will there be a list of approved PPE?
While there is no PPE that is specifically “approved” for USP <800> usage PCCA offers a selection of PPE suited for USP <800> Compliance. See our USP <800> Resource page for more information.
Can I wear my current lab coat backwards if it complies with the requirements?
Technically yes, if it were to comply with Section 7.2 of USP <800>, but we note that the gown is required to be “shown to resist permeability by HDs.”
Is a respirator required for HD compounding?
The chapter does not require the use of respirators for non-sterile compounding. See the beginning of Sections 7 and 7.5 of the chapter. It is up to the facility to decide if they are going to require the use of respirators.
Can gowns be reused?
No, gowns must be disposable. See Section 7.2
What personal PPE can we reuse?
Section 7 explicitly states “Disposable PPE must not be re-used.”
What is your recommendation on workplace attire?
PCCA offers a selection of PPE suited for USP <800> Compliance. See our USP <800> Resource page for more information.
When using N95 respirators, will fit testing and training be required per the Occupational Safety and Health Administration (OSHA)?
Yes.
Dispensing Final Dosage Forms
Are final HD compounds (e.g., hormone capsules) considered hazardous after they have been compounded?
Yes, they are still considered hazardous, and other parts of the chapter still apply. However, they no longer need to be contained in the HD lab.
Can final HD compounds be placed in automated counting machines with other non-HD compounds?
Final dosage forms of antineoplastic HDs cannot be placed in automated counting machines. For more information about this topic, please see Section 12 of the chapter: “Dispensing Final Dosage Forms.”
Hazardous drugs cannot be placed in an automatic counting machine – does this apply to both compounded and manufactured drugs, or just compounded?
It applies to both, but only if the hazardous drugs are antineoplastic HDs.
When is a non-sterile compounded preparation safe to leave a hazardous handling area? For example, if you are compounding a cream, does the ointment mill have to be within the handling area? And does the cream only leave the room once it is in its final dispensing container?
Our interpretation would be that use of something like an ointment mill is still manipulating the compound. Section 12 of the chapter states: “HDs that do not require any further manipulation, other than counting or repackaging of final dosage forms, may be prepared for dispensing without any further requirements for containment unless required by the manufacturer or if visual indicators of HD exposure hazards are present (e.g., HD dust or leakage).”
Are staff members who hand medications to patients required to comply with the chapter?
No, see Section 12 of the chapter: “Dispensing Final Dosage Forms.”
Cleaning
What decontaminant should be used to clean non-sterile compounding areas?
We are investigating agents for deactivation, decontamination, cleaning and disinfection. For decontamination, the chapter recommends, as example agents, the following: “Materials that have been validated to be effective for HD decontamination, or through other materials proven to be effective through testing, which may include alcohol, water, peroxide, or sodium hypochlorite.”
What are the requirements regarding the disposal of equipment used to compound hazardous drugs (e.g., jars, spindles, syringes, etc.)?
Any items used in the process of compounding HDs must be disposed as hazardous waste and “comply with all applicable federal, state and local regulations.” Hazardous waste removal providers should be able to guide you in how to comply with these regulations.
Receipt
Can I receive and unpack hazardous drugs in the lab?
Yes, as long as the lab is neutral/normal or negative pressure relative to the surrounding areas. However, you should also consider the implications of brining corrugated cardboard into the lab. Corrugated cardboard can be a source of microbial contamination.
Is removing a product from the box in which it was received by FedEx considered unpacking?
Yes. Receipt and receiving are covered in Sections 5.10 of the chapter.
Transport
Can we ship non-antineoplastic hazardous drugs to patients the same way we would ship other compounded products?
Sections 11.2 and 11.3, which address packaging and transport, explain that you must “select and use packaging containers and materials that will maintain physical integrity, stability, and sterility (if needed) of the HDs during transport.” Furthermore, “Packaging materials must protect the HD from damage, leakage, contamination, and degradation, while protecting healthcare workers who transport HDs.” You must also have written SOPs to cover these items.
Storage
Can I store hazardous and non-hazardous drugs in the same refrigerator in a negative pressure area?
Two refrigerators are required. Section 5.2 states, “Antineoplastic HDs requiring manipulation other than counting or repackaging of final dosage forms and any HD API must be stored separately from non-HDs in a manner that prevents contamination and personnel exposure.”
Can HD and non-HD APIs be stored in the same room if they are separated?
If this were to be done, the HD and non-HD APIs would all need to be under negative pressure. Additionally, all non-HD items would need to be treated as hazardous and comply with all of the requirements of the chapter.
Can APIs be stored in a negative-pressure cabinet?
Yes, but the negative-pressure cabinet needs to be in a negative pressure C-SEC.
Do finished preparations of hazardous drugs (e.g., progesterone capsules) have to be stored in a negative pressure room?
No.
Are bulk APIs with hazardous warnings that are not included in the NIOSH list required to be classified as HDs per site?
It depends on what is meant by hazard warnings. The chapter states, “An entity must maintain a list of HDs, which must include any items on the current NIOSH list that the entity handles. The entity's list must be reviewed at least every 12 months. Whenever a new agent or dosage form is used, it should be reviewed against the entity's list.”
Is PCCA going to adjust its labeling for hazardous chemicals?
Chemicals that are listed on the 2016 NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings have the “USP <800>” designation on the label.
Reference
1US Pharmacopeial Convention. (2016). Frequently Asked Questions: <800> Hazardous Drugs—Handling in Healthcare Settings. Retrieved from
http://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings