Coated vs. Corrugated Cardboard and Insubordiantion

On the Pharmacy Operations Blog from Pharmacy OneSource that I mentioned in an earlier post, there was an interesting thread  last week that highlighted an issue that I hear about from time to time: boxes in the cleanroom, as well as a more important issue of compliance to policies and procedures.

One person posted a question raising a concern that a technician had taken a coated cardboard box into the cleanroom that had the lid ripped off, exposing shredded cardboard underneath the coating. The tech was told to remove the box due to concerns about introducing extra particles. The tech repeated the offense a couple days later, stating that he “did not agree enough to comply”. The question was, “Am I correct (that torn cardboard should not be allowed), or am I going overboard?”

A follow-up post suggested that they allow coated cardboard in their cleanroom, but not corrugated cardboard – a position that I hear often.

Eric Kastango’s reply addressed two issues. First, concerning the box question, he suggested that if they had an operating buffer area that met USP 797 requirements, he wouldn’t anticipate that they should be particularly concerned (pun intended!) with a coated box that had a ripped off lid (see an earlier post addressing a related question about using printers, pencils, etc. in the cleanroom). However, his second point was that if the facility’s Policies and Procedures do not allow this type of boxes in the cleanroom then it is not up to the  technician to determine if they agree or not. If they do not comply, they should be disciplined accordingly.

Polices and Procedures should be updated when you find out they are outdated, but until the change is made, they must be followed!

The original forum thread can be found here (requires a free membership).

USP 797 FAQ: How large does the ante-room need to be?

From USP’s FAQ on USP 797 page:

126. Is a large ante-room required, or would a small vestibule for hand washing and donning of protective garb be sufficient? In other words, could there be an IV work room that is unclassified where the computer input, unboxing and storage of IVs takes place outside of an ante-room to reduce the square footage of space required to be ISO 7 or 8? The IVs would still pass into the buffer area through the vestibule that is the ante-room.

USP does not define the process flow requirements. A small ante room that simply facilitates hand hygiene and gowning is adequate.

Beyond-use-dating Q&A with Eric Kastango

In follow-up to the webinar he did on November 18th, Eric Kastango put together answers to the many questions about Beyond-Use-Dating  that were asked by attendees that weren’t able to be answered during the webinar before time ran out. The eight-page Q&A document is posted on Pharmacy OneSource’s site at http://www.pharmacyonesource.com/images/simplifi797/BUDQuestions.pdf.

In follow-up to the webinar he did

USP 797 FAQs: Immediate-Use CSPs

There is never a shortage of questions about Immediate-Use CSP’s, so today I’ll post a thorough review of the provision, including the six specific criteria that must be met to qualify as immediate use from USP Chapter 797 itself (and this usually answers most of the questions), distilling it down to a few bullet points, and adding several FAQ’s from USP’s website.

First the criteria:

The immediate-use provision is intended only
for those situations where there is a need for emergency
or immediate patient administration of a
CSP. Such situations may include cardiopulmonary
resuscitation, emergency room treatment,
preparation of diagnostic agents, or critical therapy
where the preparation of the CSP under conditions
described for Low-Risk Level CSPs subjects the
patient to additional risk due to delays in therapy.
Immediate-use CSPs are not intended for storage
for anticipated needs or batch compounding. Preparations
that are medium-risk level and high-risk
level CSPs shall not be prepared as immediate-use
CSPs.

Immediate-use CSPs are exempt from the requirements
described for Low-Risk Level CSPs
only when all of the following criteria are met:

1.
The compounding process involves simple
transfer of not more than three commercially
manufactured packages of sterile nonhazardous
products or diagnostic radiopharmaceutical
products from the manufacturers’ original
containers and not more than two entries into
any one container or package (e.g., bag, vial)
of sterile infusion solution or administration
container/device. For example, anti-neoplastics
shall not be prepared as immediate-use
CSPs because they are hazardous drugs.
2.
Unless required for the preparation, the compounding
procedure is a continuous process
not to exceed 1 hour.
3.
During preparation, aseptic technique is followed
and, if not immediately administered,
the finished CSP is under continuous supervision
to minimize the potential for contact with
nonsterile surfaces, introduction of particulate
matter or biological fluids, mix-ups with other
CSPs, and direct contact of outside surfaces.
4.
Administration begins not later than 1 hour
following the start of the preparation of the
CSP.
5.
Unless immediately and completely administered
by the person who prepared it or immediate
and complete administration is witnessed
by the preparer, the CSP shall bear a
label listing patient identification information,
the names and amounts of all ingredients, the
name or initials of the person who prepared
the CSP, and the exact 1-hour BUD and time.
6.
If administration has not begun within 1 hour
following the start of preparing the CSP, the
CSP shall be promptly, properly, and safely
discarded.
Compounding in worse than ISO Class 5 (see
Table 1) conditions increases the likelihood of microbial
contamination, and administration durations
of microbially contaminated CSPs exceeding
a few hours increase the potential for clinically
significant microbial colonization and thus for patient harm, especially in critically ill or immunocompromised
patients.

Boiling it down to a few bullet points (thanks to Eric Kastango for providing this summary as part of training at the Baxa STAR Center):

  • Exempt from all requirements in <797>
  • Only simple aseptic measuring and transfer are needed
  • Not more than three drug packages and NO HAZARDOUS DRUGS
  • No delays/interruptions
  • No contact contamination of ingredients or critical sites
  • Dose must be labeled if not administered by the preparer
  • Administration must begin within 1 hour after the start of preparation
  • Dose must be discarded if adminstration has not begun within 1 hour after the start of preparation. (No storing. No recycling.)

Finally, some questions from the FAQ page on USP 797’s website:

2. What types of sterile compounds can nurses prepare on the floor? Can they draw up IV push medications?

Only Immediate-Use CSPs (Compounded Sterile Preparations) may be prepared in worse (dirtier) than ISO Class 5 environments, such as in clinical patient care areas. Refer to the Immediate Use CSPs section for the six specific criteria.

3. Nurses in our practice currently mix Infliximab in the home just prior to infusion. If we receive an order for 600 mg in 6 vials of 100 mg each admixed in a 250 mL bag of Normal Saline, would this fall outside the Immediate Use CSP as defined in <797>, assuming the bag entry is limited to two?

The standards for Medium-Risk Level CSPs apply, because more than three containers of sterile ingredients are used. When there are more than two entries into one sterile container, this also qualifies as Medium-Risk Level. Increasing quantities of sterile ingredients and manipulations of them increase the risk of dosage and ingredient errors, and microbial contamination.

4. Can nurses draw up IVP medications on the nursing unit? Can they keep the left over drug in a syringe in the patient’s medication drawer for future dosing?

Intravenous medications prepared in worse (dirtier) than ISO Class 5 environments are subject to the standards for Immediate-Use CSPs. Immediate-Use CSPs cannot be stored.

5. Is there a limit of how many times a vial can be entered by a nurse using a single dose vial on a nursing unit within 24 hours?

This practice qualifies as an Immediate-Use CSP. A maximum of two stopper entries is permitted within one hour from when the preparation began for administration to the same patient.

6. Continuous infusion pumps and other devices that are filled with a single ingredient that may require multiple vials and where a Luer lock extension tubing is used to fill the catheter, can this medication be prepared in the operating room in the sterile field? Also can this preparation be administered over several days?

The requirements for Immediate-Use CSPs apply to medications prepared in worse (dirtier) than ISO Class 5 environments. Chapter <797> does not apply to clinical administration practices and conditions; however, the Immediate-Use CSPs section states a warning regarding potential harm to patients from extended administration durations of contaminated CSPs.

7. Can a product be considered immediate use risk level if product/device is administered over multiple days (continuous infusion pumps, insulin pumps, etc.)?

The Immediate-Use CSPs category does not limit the duration of clinical administration of the CSP. Please refer to the answer to question 5.

8. Which risk level would apply to vials with the stopper removed to compound for patient who are allergic to latex? They might be prepared in ISO Class 5 or outside ISO Class 5

The stopper must be removed by contacting only sterile surfaces, e.g., sterile forceps. If stopper and content removal occur within an ISO Class 5 environment, and if the vial is one of three or fewer sterile ingredients, then this qualifies as either a Low-risk Level CSP or a Low-Risk Level CSPs with 12-Hour or Less BUD, depending on whether or not the primary engineering control, PEC or ISO Class 5 source is located in an ISO Class 7 buffer area. If the vial is one of more than three sterile ingredients, then this requires compliance with Medium-Risk Level CSPs standards. If the stopper is removed by contacting only sterile surfaces in worse (dirtier) than an ISO Class 5 environment, then this qualifies as an Immediate-Use CSP.

13. In a code situation with the pharmacist preparing the drugs, what kind of labeling will be necessary?

This will usually be an Immediate-Use CSP for which labeling requirements are described in that section.

15. Is there a standard for preparing intrathecal CSPs?

Standards for compounding intrathecal CSPs are according to the particular microbial contamination risk level. The standards for Low-Risk Level CSPs are, prudently, the least that should be applied to intrathecal CSPs. While not expressly prohibited as Immediate-Use CSPs, intrathecal injections pose the greatest risk of harm and death to patients if contaminated with microorganism and bacterial endotoxins, which is most likely to occur under Immediate-Use CSP conditions.

21. Immediate use CSPs must be administered within one hour following preparation. Must administration be completed within that same hour? With low-risk level CSPs with 12 hour BUD, must administration be completed within those 12 hours?

Administration of Immediate-Use CSPs must begin within 1 hour from the start of their preparation; there is no requirement for the duration of administration. For Low-Risk Level CSPs with 12-Hour or Less BUD, there administration must begin within 12 hours from the start of compounding, but there is no administration duration requirement.

22. If a pharmacy prepares an epidural bag of bupivacaine in 100 mL normal saline, can an anesthesiologist add fentanyl to that same bag on the floor? If so, what would the BUD be?

If fentanyl is added in worse (dirtier) than an ISO Class 5 environment, then this becomes an Immediate-Use CSP, for which there is no administration duration requirement. The Immediate-Use CSPs section states a warning regarding potential harm to patients from extended administration durations of contaminated CSPs.

25. Nursing is known to mix IVPB way ahead of time for administration. What is the BUD?

The BUD for intravenous piggyback (IVPB) infusions depends on the conditions under which they were prepared. For example, when prepared under conditions of Immediate-Use CSPs, infusion must start within 1 hour of starting to prepare the CSP with no time limit to finish the infusion; when prepared under conditions of Low-Risk Level CSPs with 12-Hour or Less BUD, infusion must start within 12 hours of preparing the CSP with no time limit to finish the infusion; when prepared under conditions of Low-Risk Level CSPs, BUD is 48 hours at controlled room temperature (see USP General Notices and Requirements), 14 days at cold temperature (see USP General Notices and Requirements), and 45 days in solid frozen state between -25° and -10°, in the absence of direct sterility testing evidence that supports longer BUDs.

54. Do healthcare practitioners preparing immediate use parenteral products need to gown up, including gloves and mask?

No. Immediate use compounding is exempt from all requirements of the Chapter. That does not preclude the process of performing scrupulous hand hygiene and adhering to appropriate proper aseptic compounding technique.

80. If a nuclear medicine tech prepares a kit from a Tc99m standard preparation sent from a radiopharmacy, would this be considered Immediate Use if it is a single dose? If multiple doses is it considered Low Risk? 12 hr. BUD?

The classification of a radiopharmaceutical kit prepared by a technologist using Technetium 99m Sodium Pertechnetate sent from a radiopharmacy depends upon the environment that is used for its preparation. The kit can be prepared in worse than ISO Class 5 conditions if it is intended for a single dose use within one hour of its preparation. In this case, the technologist must comply with the six conditions specified in the Immediate-Use CSPs category. Also, the prepared radiopharmaceutical kit should not be stored for any anticipated needs.

The kit may be used for multiple doses if it is prepared as a Low-Risk Level CSP with 12-Hour or Less BUD in a segregated compounding area or better environment by a technologist that is properly prepped and garbed.

(For more about USP 797 compliance related to radiopharmacy, visit this website.)

The immediate-use provision is intended only
tially, at least annually thereafter for low- and for those situations where there is a need for emermedium-
risk level compounding, and semiannu- gency or immediate patient administration of a
ally for high-risk level compounding. Compound- CSP. Such situations may include cardiopulmoing
personnel who fail written tests or whose me- nary resuscitation, emergency room treatment,
dia-fill test vials result in gross microbial preparation of diagnostic agents, or critical therapy
colonization shall be immediately re-instructed where the preparation of the CSP under conditions
and re-evaluated by expert compounding person- described for Low-Risk Level CSPs subjects the
nel to ensure correction of all aseptic practice patient to additional risk due to delays in therapy.
deficiencies. Immediate-use CSPs are not intended for storage
Media-Fill Challenge Testing—The skill of for anticipated needs or batch compounding. Preppersonnel
to aseptically prepare CSPs may be arations that are medium-risk level and high-risk
evaluated using sterile fluid bacterial culture me- level CSPs shall not be prepared as immediate-use
dia-fill verification3 (i.e., sterile bacterial culture CSPs.
Copyright 2007 The United States Pharmacopeial Convention All Rights Reserved.
Revision Bulletin á797ñ Pharmaceutical Compounding—Sterile Preparations 13
Immediate-use CSPs are exempt from the re- tient harm, especially in critically ill or immuquirements
described for Low-Risk Level CSPs nocompromised patients.
only when all of the following criteria are met:
1. The compounding process involves simple SINGLE-DOSE AND MULTIPLE-DOSE
transfer of not more than three commercially CONTAINERS
manufactured packages of sterile nonhazard- Opened or needle-punctured single-dose conous
products or diagnostic radiopharmaceuti- tainers, such as bags, bottles, syringes, and vials of
cal products from the manufacturers’ original sterile products and CSPs shall be used within 1
containers and not more than two entries into hour if opened in worse than ISO Class 5 (see Taany
one container or package (e.g., bag, vial) ble 1) air quality (see Immediate-Use CSPs), and
of sterile infusion solution or administration any remaining contents must be discarded. Singlecontainer/
device. For example, anti-neoplas-

USP 797 FAQ: Beyond-use Dating for IVPB’s

The BUD for intravenous piggyback (IVPB) infusions depends on the conditions under which they were prepared.

  • When prepared under conditions of Immediate-Use CSPs, infusion must start within 1 hour of starting to prepare the CSP with no time limit to finish the infusion
  • When prepared under conditions of Low-Risk Level CSPs with 12-Hour or Less BUD, infusion must start within 12 hours of preparing the CSP with no time limit to finish the infusion
  • When prepared under conditions of Low-Risk Level CSPs, BUD is 48 hours at controlled room temperature (see USP General Notices and Requirements), 14 days at cold temperature (see USP General Notices and Requirements), and 45 days in solid frozen state between -25° and -10°, in the absence of direct sterility testing evidence that supports longer BUDs.

For more information about BUD’s register for Eric Kastango’s “Demystifying BUD’s” webinar on 11/19/09 at www.rph.com/webinars. The webinar will be recorded for future access as well.

You need to roll THAT dirty air compressor into my cleanroom to certify my hood??

Someone forwarded this message to me from the ASHP listserv… thought I’d post it here in case it benefits anyone else:

Question:
I need advice from those familiar with NST testing of BSC. A new technician came by my cleanroom to certify my 4 foor NuAire vertical floor hood. He couldnt figure out how to get his wagon into the room. He insisted that he needed a heavy duty oil-based compressor and Craftsman wheeled toolbox to certify the lack of leaks in the exhaust filter. A no point would I allow a greasy, rusty metal cart strolling and spewing oil fumes in my pristine cleanroom. My hoods have been certfied for over 10 years without the use of such a device. The technician insisted that this is the NST standard that they must put air pressure on one side of the filter to check for leaks and since I was so inflexible, he would not certify that criteria. Does anyone know how this test is supposed to be done and how I could get this test conducted without allowing this device to soil my cleanroom?

Answer provided by Jim Wagner:
My first assumption is that the NST certification they are referring to is actually NSF (formerly National Sanitation  Foundation now NSF International).  The concern is that he feels the certifiers compressor should not be taken into the cleanroom.  My concern is the fact that the BSC was certified for 10 years without a compressor.  Compressed air is needed to drive air through the laskin nozzle generator used to create the appropriate aerosol challenge for leak testing HEPA filters in all primary engineering controls including BSCs.  I don’t have a problem restricting the amount of material that goes into the cleanroom but a minimum amount of equipment is needed for  this task.  The equipment should be disinfected before it is taken into the cleanroom.  Also, the individual components can be taken off the certifiers cart and placed onto a cleanroom cart.  I applaud the certifier for refusing to certify the hood without the appropriate equipment but wonder why they did not find an accommodation like using a clean compressed air line and leave the compressor in the hallway.  BSCs should be certified to NSF international standard 49 by NSF accredited technicians.  I would also like to offer the attached certification matrix to direct the facilities  to the appropriate cleanroom certification criteria.

Jim Wagner
Controlled Environment Consulting
2527 Kings Mill Rd
Hellertown, PA  18055
ph.  484-852-0310
fx.  484-852-0311
jimwagner@cenvironment.com

Feel free to contact Jim directly with any other questions or for a copy of the certification matrix that he refers to. He’ll be happy to help! If anyone is looking for a new certifier, he is as qualified as they come.

USP 797 FAQ: Dating Multi-dose Vials

From Eric Kastango’s article in the recent Cleanrooms & Compounding issue of Pharmacy Purchasing & Products magazine (unfortunately, it doesn’t appear to be online yet – but several other excellent article related to USP 797 are available online):

There continues to be significant confusion regarding the storage period for multi-dose vials subsequent to their initial puncture. Many organizations have been cited by The Joint Commission, state boards of pharmacy, and departments of health for not discarding multi-dose vials after 28 days. The Multiple-dose Containers Section of USP Chapter <797> states that the “BUD for an opened or entered (e.g., needle-punctured) multiple-dose container with antimicrobial preservatives is 28 days (see Antimicrobial Effectiveness Testing <51>), unless otherwise specified by the manufacturer.” Many organizations have missed the “unless otherwise specified by the manufacturer” part of the section. The CDC’s Vaccine Storage and Handling Toolkit is an excellent resource on the storage and handling of vaccines. The CDC states, “a vaccine or diluent may be used up to and including the date on the vial unless otherwise stated in the product package insert.”