Q & A Follow up | Achieving Compliance to USP <800>

Questions and Answers with:

Lou Diorio, RPh, FAPhA, Principal, LDT Health Solutions

 

Q: Must devices used for manipulation of nonsterile HD’s be placed in a negative pressure room (- 0.01-0.03)?

YES – (USP <800> section 5.3.1 – a PEC must always be contained inside an SEC.


Q: ­C-SCA- must be negative? ­

YES for HD compounding. USP <797> also allows the creation of SCAs for non-HD compounding as well, with slightly different environmental requirements. – USP <800> References: Sterile section 5.3.2.  & 6


Q: ­Do you have to have a respirator available for receiving of HD’s like tablets in bottles or other HD that are in final dosage forms? ­

YES because you may not know the contents of a box simply marked as containing HDs, once you determine that the HD within are on your list of HD drugs which you have alternate work practices for, then you can remove the N-95 respirator – USP <800> reference section 10 Receiving


Q: ­Do N-95 masks need to be fit tested? ­

If your inventory contains drugs which volatilize at room temp then disposable N-95 respirators are not suitable. In that case the more elaborate N-95 reusable masks are in order. YES- to protect the employee they must be fit tested. There are several resources available from the mask manufacturers, that you can find quickly on the web. If your organization is large enough for this task to be frequent enough you may want to get one or more employees certified to conduct the fit tests for your organization.


Q: ­Could you please define a neutral area? ­

USP <800> Section 5.1 Receipt, states; “Antineoplastic HDs and all HD APIs must be unpacked (i.e., removal from external shipping containers) in an area that is neutral/normal or negative pressure relative to the surrounding areas. HDs must not be unpacked from their external shipping

containers in sterile compounding areas or in positive pressure areas.” I would consult with your risk management or buildings operations folks, but the short answer is- – – an area that is not positive pressure to the surrounding space.


Q: ­When tablets are counted we wear gloves for counting. What about when they are taken to the front counter and the RPh pours a tablet into the cap of the bottle for a final check. Is there also concern about trace waste on the outside of the final bottle? ­

I would not continue that practice as it opens the impervious plastic contain needed to comply with <800> and exposes the pharmacist and surrounding personnel to possible exposure. You must perform an assessment of risk and make that determination for your Pharmacy. I would consider another practice to satisfy the double check all pharmacists conduct before release of any prescription. Once that process is established educate and document all involved staff to standardize practice. You can also establish as your standard practice the purchase / use of unit-dose packaging for all HD drugs.


Q: ­Regarding HD storage room, does it need to be certified? ­

Strictly speaking, you are not “certifying” a non-ISO Classed room (unless the storage room you are speaking about is your BUFFER room for sterile HD compounding. If the case is that this room is being used as an HD storage room then you should as part of the certification process for any ISO classed compounding areas you have on-line, you should have your certifier validate that the storage room is performing according to your specifications, (proper pressurization, ACPH etc.) which of course should reflect the requirements within USP <800> for the segregated storage of HDs. See USP <800> sections 5-Facilities & Engineering controls (5.2 storage) Please remember the general drug storage requirements as well which you find within your State’s practice Act and USP <659> Packaging & Storage Requirements.


Q: ­I thought that only antineoplastics had to be stored separately in a negative room­?

Untrue, you need to conduct an assessment of risk and establish alternate work practices for any HD agent that you wish to store in an area outside your containment HD storage room. See USP <800> sections 5-Facilities & Engineering controls (5.2 storage) Please remember the general drug storage requirements as well which you find within your State’s practice Act and USP <659> Packaging & Storage Requirement.


 Q: ­Can we use the same agent for both deactivation/decontamination and cleaning? ­

If you determine in your assessment of risk that the same agent is appropriate for both the deactivation and decontamination then you can use it for both steps. However, the two steps much be separate and distinct (two applications and two removals of the surface contaminants as distinct actions). Cleaning is another matter, one you have deactivated & decontaminated the area in question, cleaning becomes your standard process from the beginning per your policy & procedure, using the agents you have already identified as appropriate for this task. Additionally, do not forget if you are speaking about sterile compounding then the cleaning phase must be followed by a disinfection process per <797> and your policy.


 Q: ­H2O2 and Sodium Hypochlorite actually DO NOT decontaminate most hazardous drugs.  Are you aware of any chemicals that truly decontaminate hazardous drugs? ­

I am a pharmacist, not a chemist nor an industrial hygienist, however there are resources out there to assist us in daily practice. The first place to start is the drug’s prescribing information. From Patricia C. Kienle’s Chapter 800 Answer Book we find these comments:

“Few drugs have specific deactivators. Traditionally, bleach has been used for this purpose. If the drug has a specific deactivator listed in the product labeling, use it after manipulating

that drug.” As well as, “Many SDSs recommend decontamination with sodium hypochlorite (bleach). Other commercial products are also available, including those designed for decontaminating hazardous drugs. Alcohol does not deactivate hazardous drugs and can spread contamination if used prior to deactivation.”

Consulting these and other authoritative references from OSHA & NIOSH should lead you to the correct answer for your situation.


Q: ­What was said about the training program? ­

Please see Personnel Training USP <800> section 9. Basically, it must be conducted before people working independently, repeated annually, and be properly documented. The program must be reviewed each year for accuracy and completeness.


Q: Where we can find the 7 minute videos that we can use for training?

The training videos mentioned for PPE donning and doffing (are specifically for Ebola) and can be found on the CDC website or in the reading list at the end of the presentation slides


Q: ­If we use pass through chambers from the ante to the negative buffer room, is this chamber subject to air quality testing?  If so, how would this be conducted? ­

See chapter <800> section 5.3.2 Sterile Compounding, and section 6 Environmental Quality and Control for more details. Also, a competent and qualified CETA certified professional certifier can assist you.


Q: ­Eye Wash; I thought it was at least 3 minutes continuous testing, not 5 min?

Complete OSHA requirement for eyewashes can be found on the web on the OSHA website. [It’s actually 15 mins of running tepid water.]


Q: ­Question on the externally vented room for HD compounding? If there are BSC-II in the room that are externally vented then does that meet the requirement? Or do you also require that the room itself be separately vented to the outside? ­

A competent and qualified CETA certified professional certifier can assist you, as well as an Engineer or Architect, since there are some differences in local building codes.


Q: ­Can the hoods have 12 inches opening for non-sterile HD cpds? ­

If you are referring to the sash height of your BSC (PEC), the answer is that you should refer the PEC’s operations manual for that data, and have the device certified to the specification of the particular PEC by a competent and qualified CETA certified professional certifier.


 Q: ­It is a must to have a sink in the gowning room? ­

The location of the sink is dictated by local BOP regulation, USP <797> as well as <800> for HD compounding. Depending upon the type of HD comping you are referring to, sterile or non-sterile the location can vary. Please see USP <800> section 5.3 Compounding – for more information


Q: ­If compounding misoprostol powder for equine use. What precautionary labels should be placed on the Rx label?  ­

Labeling of any preparation HD or not should always be consistent with your local State BOP as well as USP requirements (including USP <800>). The matter of the preparation being for animal use (non-feed animal) does not alter those requirements.


Q: ­Is the respirator required a “surgical respirator” or is it a canister respirator? ­

That depends upon your assessment of risk and drugs you are handling. N-95 respirators come in many shapes and sizes, and must be matched to your application. Disposable N-95 respirators are not suitable for drugs which volatize at room temperature. Since N-95’s provides protection against airborne particles. It does not protect against gases or vapors.

There are other respirators that may meet your needs, which you should determine for your application. Other types include full-facemask, chemical cartridge-type respirators, elastomeric half-mask respirators with multi-gas cartridges and P100 filters (or a cartridge targeted to the specific drug), or PAPRs.


Q: ­Can you please go over the CSTDs which “should” and “must” be used. Do you need to use it within the CACI/BSC in a compliant clean room? ­

The use of CSTD’s or so-called supplemental engineering controls is covered in USP <800> in section 5.4. please be aware that no universal standards for these devices yet exists. Although NIOSH does have a draft document on the subject publicly available. You should consult these and other relevant resources to determine which CSTD meets your needs. The “should” and “shalls” are within USP <800>. Since USP <800> as with all USP general chapters represents the minimum practice standards you should determine for yourself and your organization at what level you wish to practice.


Q: ­Do you recommend a respirator for cleaning under the deck? ­

The use of PPE for all operations within your HD compound room(s) /area(s) including cleaning & disinfection is required so, YES.


Q: ­You had mentioned some complimentary training links.  Can you recommunicate which organization offers those, via our tax dollars? ­

That is the CDC- they are specifically for the donning & doffing of PPE for Ebola patients, but they are good and free. A short Google search will get you to them. The links are also on the reading list slide of my presentation.


Q: ­When will physician offices and stand-alone infusion centers be held accountable to these standards?

­YES, USP <800> as with ALL USP chapters is a federal standard and the scope of USP <800> is ALL healthcare workers who handle or may come in contact with these agents. So, all these locations will have to comply. Please see section 1. Introduction & Scope within the chapter the second paragraph of the chapter is pretty clear in this area!


Q: ­Can assessment of risk be down globally and/or by category or does it need done on each hazardous drug individually? Does it have to be signed by each employee handling hazardous meds? ­

The risk assessment of risk and how it is done is up to you. IF you are comfortable grouping agents by class then, it is OK. If you are not comfortable with this approach or if you are concerned that an individual moiety is somehow different then it becomes a line-by-line process. The notification of employees is done through the signed attestation that is required upon hire. Unless required by local statute or your internal process only the most responsible person in your operation needs to review and certify the annual review of the risk assessment.


Q: ­Will the monthly testing of an eyewash located within a buffer area increase the risk of contamination? ­

YES, any release of water within a controlled area is a concern. But the statutory requirement is there per OSHA. I would consult with your life safety, risk management personnel and the eye wash manufacturer to see how this can bet be done with minimal impact to the controlled spaces. Careful monitoring of your environmental monitoring data is in order to be sure that these tests are not negatively impacting your compounding operation.


Q: ­Is “FIT Testing” required. Do you know of a company that does that? ­

If your inventory contains drugs which volatilize at room temp then disposable N-95 respirators are not suitable. In that case the more elaborate N-95 reusable masks are in order. YES- to protect the employee they must be fit tested. There are several resources available from the mask manufacturers, that you can find quickly on the web. If your organization is large enough for this task to be frequent enough you may want to get one or more employees certified to conduct the fit tests for your organization.

Not the only company but the biggest is 3M, you should do an internet search in your area or call the local DOH for more information.


Q: ­I thought wipe sampling was a should­? ­How will we test the swabs to verify our cleaning processes are correct?  ­

Wipe sampling is a “should”. I believe my comment during the presentation was that since there are other priorities that have longer implementation time lines (i.e. physical plant alternations) and since there is some discussion about how and who can process these tests it should be part of your overall plan just not the first item you tackle. You should watch the professional journals and other resources for demonstrated best practices to see how best to set-up these testing programs. As well as how to interpret and react to the data collected.

 The presence / absence of wipe testing will verify your processes are meeting the standard and are probably sufficient.

 In the case of environmental monitory & viable and non-viable air sampling, analysis of this data will help you ascertain that your cleaning is maintaining the proper state of control within your compounding spaces.


 Q: I may have missed the mention of it, any prediction on when USP 797 revisions will be adopted and made enforceable­?

No crystal ball predictions, however the USP has stated publicly that over 3500 commenters participated in the last draft process and that there were more than 10,000 individual comments to be considered. My experience tells me that a chapter release without another public comment period from the resulting draft is highly unlikely. Having said all that, I think it may be awhile before the chapter is revised. In the meantime, I would suggest focus on compliance to the General Chapter in place.


Q: ­For clarification, an external HEPA Filter is not required in addition to the HEPA filters on a CACI? ­

Correct, the information regarding the Errata document published in March 2016 by USP clarifying the error in the chapter released in February 2016 is viable form USP (www.USP.org)


Q: ­Are there closed system devices for non-sterile oral HDs prepared in oral syringes? ­

Not that I am aware of, however new products are being released every day. I would search the web. Another good reference is Pharmacy Purchasing and Products magazine, they have a product search feature called – “Find-It” you might find useful, they can be found at www.PPPMag.com


Q: ­I thought googles were only required when the sash was up or there was a splash risk? ­

I would say NO, use of PPEs and eye & face protection is covered within section 7.4 of USP <800> I think it risky to try and determine when a problem is going to occur. Your risk management personnel, HR department and administration may want to weigh in on the potential risks, I think the risk/benefit ration in this case is clear, and in the case especially of sterile compounding I don’t want my compounding personnel taking on and off as well as handling anything that can be avoided.


Q: ­Do you see repackaging of HD oral solids (tabs) and splitting of these items only being allowed in the Vented hood within the negative pressure room­

YES, that is what is emerging as standard or best-practice for the crushing and splitting of HD drugs. This is NOT a function that nursing can be doing routinely on the units. In fact, in cases where facilities have no non-sterile HD compounding spaces, they are bringing these function into the HD sterile compounding rooms. There is a scheduling, training, and education component of course but the use and maximization of the containment spaces in reducing potential employee exposures in these cases is paramount.


Q: ­What is your opinion on the need for a compounding supervisor? ­

The chapter specifically only mentions a “compounding supervisor” only once: “Compounding supervisor: Individual(s) responsible for developing and implementing appropriate procedures; overseeing facility compliance with this chapter and other applicable laws, regulations, and standards; ensuring the competency of personnel; and maintaining environmental control of the compounding areas.”

 The organization needs a person to oversee the global plan for USP <800> compliance for the organization. The Pharmacy needs a point-person to fulfill the above-mentioned duties for the pharmacy department since this is the area (including its satellites) where most of the compounding is happening. Like with USP General Chapter <797> the responsibility for compliance rests with the Pharmacist-in-Charge (or whatever term your BOP statutorily employs) so in the absence of the PIC identifying another individual to assist with compliance all these duties fall to the PIC. Although the PIC cannot abdicate his/her fiduciary responsibility to the compounding supervisor, they are the person who is there in the compounding area(s) more than the PIC and are essential for the long-term success of any quality assurance, or quality management efforts.


Q: ­Does USP 800 speak to expectations in terms of cleaning glassware used in compounding HD? Dishwasher? ­

Not specifically, but it does speak about cross contamination and the rationale for keeping any contaminated devices within the USP <800> containment room makes the greatest sense. When considering non-sterile HD compounding glass ware especially, if the volume of your glassware is low then you should establish a process / risk assessment for processing the glassware to where you clean you other non-HD vessels. (containing the vessel in a plastic bin with a lid for example, once it’s been deactivated & decontaminated) You need to be sure that this process does not allow all your glass ware to become contaminated, nor do want to drag contaminants throughout your general pharmacy. If your volume of glass ware is large enough I would think that placement of a dishwasher in your HD non-sterile compounding area is a good investment.


Q: ­Please comment on use of PAPRs as an alternative for respirators (positive air pressure respirators) ­

Please see USP <800> section 7.5 Respiratory protection.   Use of these PAPRs depends upon your assessment of risk and drugs you are handling. Generally, N-95 respirators come in many shapes and sizes, and must be matched to your application. Disposable N-95 respirators are not suitable for drugs which volatize at room temperature. Since N-95’s provides protection against airborne particles. It does not protect against gases or vapors.

 There are other respirators that may meet your needs, which you should determine for your application. Other types include full-facemask, chemical cartridge-type respirators, elastomeric half-mask respirators with multi-gas cartridges and P100 filters (or a cartridge targeted to the specific drug), or PAPRs.


Q: ­Do you have average (ball park) cost estimates for USP 800 renovations (say 100-200 bed Hosp, 201-300 bed, > 300)?  ­

NO, I would not hazard a guess here. You cannot base any estimate on bed size, the most accurate determinate is through-put (capacity) of the cleanrooms instead.

I can tell you that the environmental controls, (HVAC, pressure, & humidity) and the ventilation (duct work) are the most costly elements of these projects. Cleanroom construction should NOT be undertaken in haste. A clear custom design criteria should be established by a competent and experience pharmacy consultant guiding the engineering and architectural resources on project team. Without the design criteria driving the project and used as the final check at the end of the project the organization is at the mercy of the cleanroom vendor / provider (or component providers). Any monies spent in this manner, will be less than the monies spent from the contingency reserves in areas where details are missed, or design elements are chosen incorrectly.


Q: ­Can we use PAPRs? ­ ­Which type of filter is best for the reusable respirators? ­

Please see USP <800> section 7.5 Respiratory protection.   Use of these PAPRs depends upon your assessment of risk and drugs you are handling. Generally, N-95 respirators come in many shapes and sizes, and must be matched to your application. Disposable N-95 respirators are not suitable for drugs which volatize at room temperature. Since N-95’s provides protection against airborne particles. It does not protect against gases or vapors.

There are other respirators that may meet your needs, which you should determine for your application. Other types include full-facemask, chemical cartridge-type respirators, elastomeric half-mask respirators with multi-gas cartridges and P100 filters (or a cartridge targeted to the specific drug), or PAPRs.


Q: ­ Do you see a trend of fungal contamination when the refrigerator is moved into the buffet room? ­

Not yet, but perhaps that is because most organizations are not yet stepping up the frequency of their environmental monitoring. If you need to store regulated HD then a refrigerator is required, and it should be properly sized to accommodate your drug stock. If you don’t need one it is NOT required to be in there, if you do then it should be big enough but no too large. You need to design for it, properly positioned low wall return(s) near the fridge, a proper cleaning protocol (weekly minimum) and good training of personnel should be backed by environmental monitoring in proximity to the fridge.


Q: ­We have a separated ante room before entering the separated clean room for compounding chemo. Can we make this ante room negative pressure so that we can store HD? ­

Not really sure what your layout looks like. But if you are asking if you can use a dedicated negative pressure ante as your storage room. If it is dedicated, then you can use it in that way however you must remember that a room used in that way will require you don & doff HD PPE each time you enter the ante, even if it is for a moment. If you use the buffer for that then the PPE requirement moves into that area and the use of the ante-room changes.


Q: ­Employee are anxious about potential HDs exposure and surveillance results. Any suggestions on how to address this concern? ­

This is an area that is under discussion & development and must include your HR folks. They are the most capable in the notification and communication with employees on technical and legal matters. I can see a time where there are more best-practices published and your legal counsel and HR professional(s) working with the clinical professionals will have a more holistic and polished approach. I think that the science needs to meet with education, and only thorough informed personnel working with employers can this work long-term. The conversation is bigger that any one pharmacy department, and you need to expand it to include some of the resources mentioned to get the right response.


Q: ­Are we required to store and mix non-antineoplastics in the same room and hood as antineoplastics? ­

If these non-antineoplastics are mixed in the same PECs as your antineoplastics you work practices and standard processed


 Q: ­Hospitals that are starting the first step of developing a list for the facility would have an easier time if we had multiple examples to look at from other hospitals.  Do you know how we can get examples of HD lists developed by other hospitals? ­

Professional organizations, and their message boards, associated blogs and websites are a great place to start sharing that kind of information. ASHP, APhA nationally, and their local affiliates (State Pharmacy Associations) are a good source of information as well. Professional trade journals and their archives will have solid drug information as well. Don’t forget Pharmacy Purchasing and Products Magazine (www.PPPMag.com) is a free resource that has a pretty large archive of technical and scientific artless that you may find valuable.


Q: ­When administering a listed hazardous drug in tablet and capsule dosage form to patients from a unit dose package is it required for nurses/those who administer, to use gloves if the technique is to transfer med to a soufflé cup for administration? ­

YES, I believe it is as you need to make reasonable accommodations for employees to protect them.


Q: ­You mentioned that you knew of states that had already adopted USP 800. Can you share which states those are? ­

My comment was that some State Boards were enforcing part of their own statutes, rules or regulation that incorporate elements of USP <800> or other OSHA regulations (i.e. exhausted PECs, negative pressure compounding areas, segregation of inventory etc.) Most notably NJ, CA, VA, and OH have been inspecting and levying fines, and other discipline.


Q: ­Medical Surveillance: Guidance?  Where do you begin? ­

This is one of those areas where resources outside of the Pharmacy will be key. HR, administration, employee health, legal, among other resources must collaborate and determine the breadth, and scope of the organization’s program. I would think as we get closer to the July 1, 2018 date more information and resources will be published.


 Q: ­It is my understanding that OSHA requires all employees performing jobs that “require” respirator use to be fit tested, regardless of respirator type (disposable vs. reusable).  Is this correct? ­

Yes. Fit-testing of N95 respirators is required by the Occupational Safety and Health Administration (OSHA) respiratory protection standard (29 CFR 1910.134) when workers could be exposed to hazardous particles or vapors and engineering controls are not feasible (e.g., cleaning up a spill), but often pharmacy personnel are inadvertently excluded from that procedure. Contact your employee health office to let them know that receiving and pharmacy personnel and nursing personnel who handle HDs need to be included in the organization’s N95 fit-testing.

(from the USP <800> answer book – by P. Kienle)


Q: ­What would be your recommendation for table 3 NIOSH drugs and crushing? ­Can HDs tab stock bottle like Xeloda be stored in MedCarousel? ­

Crushing or splitting solid doses would be handled in the same way. If these drugs are on Table 3 (reproductive hazards) in the National Institute for Occupational Safety and Health (NIOSH) list of HDs. All containment strategies in <800> are required unless you consider this in your Assessment of Risk. (i.e. segregated storage, negative pressure room etc.)

If you include it in your Assessment of Risk, you could consider some of these approaches:

Define restrictions concerning who may package the doses, based on the reason that the drug you are packaging is on the HD list.

Dedicate a specific tablet splitter only for HD use.

Develop a method to place the split (or crushed) tablets in a consistent packaging system (e.g., a manual unit-dose bubble or impervious plastic baggie).

Label the bag with whatever caution is required by your Assessment of Risk.

Place the doses in a lidded container on your shelf with a warning on the lid.

(Adapted from the USP <800> answer book – by P. Kienle)

 

Q: ­When using a reusable respirator for C-PEC cleaning how do you decontaminate and store in between use to prevent contamination of the inside of the respirator? ­

Firstly, disposable PPE like disposable respirators, must never be reused. Reusable PPE (like some respirators) must be decontaminated and cleaned after use, please refer to the manufacturer’s instructions for details. This process should be incorporated into a policy & procedure and included in your employee’s training.


Q: ­In terms of dry heat sterilization of compounded HD, would the oven then need to be placed in a negative pressure room? ­

If you are referring to HIGH risk compounding and the use of heat sterilization of HDs YES you would have to place the device within a negative pressure area to maintain both sterility and containment of any HD particles, residues or gages created during your sterility processing protocol, per USP <797>, also see USP <85> & <1211>.


Q: ­Our organization performs high-risk non-antineoplastic HD compounding.  Our clean room design plan is to create a negative pressure anteroom in addition to our existing negative pressure ISO7 room.  Do both rooms need to be externally vented separately? ­

That depends, the exhaust system that must be created with the proper conditions is described within USP <800> Section 5. Facilities & Engineering Controls. You should consult with a qualified engineer, HVAC contractor or architect with experience in the set-up and operations of these types of systems. There are probably local building codes that will also come into the conversation as well as USP and BOP requirements so you will need to consult a specialized expert in these matters to design build, and certify these systems.


Q: ­Can a pass-through refrigerator with interlocking doors be between HD cleanroom and ante-room? ­

NO- See USP <800> Section 5.3.2 Sterile compounding


Q: ­If tablets are split, but then packaged in an air tight packaging, do they still need to be stored separately? ­

No. If stored in impervious plastic and handled properly you can include this work practice in your assessment of risk and not segregate them. But you must document the work practice within your assessment.