Visual Inspections of Compounded Preparations

Pharmacy Stars RxCompounding Compliance B!tes weekly newsletter. Simplifying the complex world of pharmacy compounding compliance by Fred Massoomi, Pharm.D, BCSCP, FASHP

Friday June 21, 2024 Vol 1 Issue 3

Visual Inspection of Compounded Preparations

I had the opportunity to sit in on an awesome webinar on the visual inspection of compounded preparations by personnel: “Hiding in Plain Sight: Visual Inspection of Compounded Preparations” by Lindsey Lepard, Pharm.D. Director of Clinical Education AIS Healthcare : Link to presentation. Yeah, I know, not a topic that we think we need a whole lecture on the surface; but it is one of the most IMPORTANT tasks we perform in providing patients with safely compounded preparations.??

The ’inspection’ process is often relegated to ‘does the label match the medication order’; or ‘does the drug listed on the label match the vial presented’; or ‘does the final product look somewhat clear’.? Many variations of visual inspection can occur; but in the end we are looking for a combination of what is listed in ADDITION to what happens at each step of the process.?

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Visual inspection really should go beyond the ‘label’ and be done by folks directly involved with compounding, checking and the administration of drugs as part of the quality control process.

USP lays out when it must occur for compounded preparations.? What we see in? USP <795> in my opinion is the more difficult of the processes for visual inspection.? Unlike injectable medications where in most cases the fluids are clear and containers allow for inspection of the contents, that is not the case for compounded non-sterile preparations.? Visual inspection expectations are critical and must be defined in the Master Formulation Record and documented in the Compounded Records. USP gives examples of ‘color, texture, physical uniformity’ into the inspection process in addition to any testing that may also be required.? The days of just ‘mixing’ two ointments together or crushing a tablet to formulate a liquid formulation now requires more robust checks and information.? Also, the type of formulation, like emulsions, suspensions, may require more checks prior to release.??

USP <797> interestingly ties in the visual inspection process as part of the competencies within the media fill process where we are looking for ‘turbidity or other manifestations’ from the process to the products for patients. In the section on component selection sites must institute a visual inspection of components that cannot be obtained from an FDA-registered facility prior to use.? The visual inspection process is part of the compounding record elements and part of the release testing procedures as part of the quality control processes.? USP <797> does devote a small section to ‘Visual Inspection’ which occurs at the end of the compounding process and another inspection that must occur before the compounded preparation is released AND at the time of dispensing (if the time is different from the release time). Dr. Lepard lays out the elements that are required for the inspection of the compounded prep as defined by USP but goes into detail into the supporting USP chapters USP <1> Injections and Implanted Products, USP <790 Visible Particulates in Injections and USP <1790> Visual Inspections of Injections.

USP <800> states ‘visual inspections’ with regards to safety for receiving of products from vendors and prior to dispensing to minimize hazardous drug exposure.? Noting that as USP <800> sits on the shoulders of USP <795> and USP <797> the standards on visual inspections for the corresponding compounded preparations apply.

Sites must have the visual inspection processes as part of training for personnel involved with the compounded preparations: from inspections of components (medications, API, supplies) to the administration of the preparations.? In this process we need to determine the following:

1. The physical appearance is as expected (no particulate, discolorations, precipitants)
2. The labels match medication order (right ingredients, right supplies, right calculations)
3. The container closure system integrity (no leaks, cracks, defects)

Interestingly, Dr. Lepard provided a nice discussion of the use of aids to assist with the inspection process like proper lighting, use of black & white backgrounds, inspection booths/boxes, magnifying glasses etc.? Basically, providing staff with tools to assist in this process.? I have had the opportunity to visit hundreds of compounding locations and I often have found these tools with significant layers of dust, not hooked up to electricity, bulbs burnt out, magnifying glasses so opaque with scratches that in the end leads to discouragement of staff to use these tools.

Automation brings another wrinkle to consider in the process.? If a robot compounds a product does this inspection need to be robust?? In my opinion, more so.? There is the potential for these devices to damage the containers during the compounding process or for the drugs themselves from the manufactures to have issues (coring, glass particles, metal shards, etc.).? So, inspection is still relevant.? For sites with IV workflow systems, VISUAL inspection of the physical product is still key to this process.? Sites really need to ask, ‘is a remote video inspection just as good as a physical inspection’?? Knowing some systems have magnification and image enhancing tools, are these good enough?? Sites would be best suited in validating (yes, I used a cGMP term) the ability of these systems to identify a multitude of possible scenarios.

Dr. Lepard did address ‘automated’ visual inspection devices, noting they really are designed for high volume compounding and are extremely expensive at this time.? And, like equipment we bring into any process, the equipment itself brings variation and new issues that must be addressed and mitigated.

Training for these types of inspections must be defined by institutions where they define who gets trained, what they get trained on, what to do if there is a deviation and on-going training.? Dr. Lepard did note that there are ‘training kits’ out there for purchase: Knapp Kits which gives examples to share with staff.? Sites should also take pictures/videos of products known to have issues: TPNs with precipitate, TPNs where the emulsion cracks (wow, that one dated me), coring of vials, color variations (noting lots of vancomycin injection vary in color between manufactures from light tan to clear <days of Mississippi Mud are hopefully gone>.??

Pictograms of Common Unacceptable Particulate Matter

Hazardous drugs should undergo the same robust inspection.? Physical inspection (not through a Ziplock bag) is so key for safety with this vulnerable population.

Often nursing is pretty keep on what products should look like and they are never shy about reporting issues…for all of our sake thank goodness.? A perfect example of where inspection and monitoring during drug administration is important is the incident where busulfan started to degrade the tubing-set; which lead to the investigation of the IV-line compatibilities and closed-system drug transfer device testing.??

So, what are steps sites can take to formally address the ‘visual inspection’ process.? Dr. Lepard provided some great pearls:

1. It starts with the culture; a culture of quality must be weaved into every part of a compounding program.
2. Review Master Formulation Records and Compounding Records to ensure they provide a description of how
3. Define who is involved in ‘visual inspection’ processes.? Noting it starts at the receiving area, through the movement of materials process, to compounding, to checking to administration.
4. Ensure staff have access to the proper tools that are in good condition.
5. Get a timer, some states and accreditation bodies require the extremely randomly selected 5-seconds for each side of a product…sure there is a study out there somewhere.
6. Define the training program and what competency means.
7. Develop and SOP the CLEARLY outlines each step; not just ‘visual inspect’.? Try to incorporate ‘swirling’ the mixture, comparison against black and white backgrounds, magnification, inspection of ports, etc.? And for those sites in certain states, inspect each side for 5-seconds!
8. Incorporate the inspection of the label and what that process means.
9. If robotics and IV workflow systems are used clearly define how the visual inspection process it to work; physical vs. virtual
10. Define what steps need to take place if something does not look right; the documentation and notification processes.
11. Dr. Lepard brought up ‘eye exams’; and to throw the kitchen sink in ‘what about color blindness’?? Do staff have the visual acuity to identify issues?? Great discussion points for sites with their human resources departments (NOTE: not required by USP)

With the new revisions to USP, sites really need to think about the visual inspection processes and what that really means and how do you train for it.??

Dare to Share That SOP

This week’s SOP to share is an example of how to template and use an example, albeit from an article, of visual inspections for sterile preparations.? Use the template for the guidance based on USP standards but modify and personalize to include examples from your location of what products should look like, but more importantly what to look for when products should not be used.

Link: Visual Inspection & Verification of Compounding Accuracy

Hey Houston, Do We Have a Problem?

Cause: Pharmacy spaces are extremely limited and days when there is just a lot going on, staff will always find ways to make things easier.

Effect: Drugs and supplies used for compounding drugs should not be jammed up next to the HEPA and, the amount of exposed supplies may lead to cross contamination with other preparations during the compounding day.? Wonder what the process is for disinfecting and cleaning the work surfaces in this scenario?

Increasing the Gray Matter

FDA 11th?Annual Report on Drug Shortages?

“Food and Drug Administration (FDA) has presented its 11th?Annual Report on Drug Shortages to Congress with data through the end of 2023.”? And here is a link to the FDA Drug Shortages website listing all shortages ‘reported’ to FDA, noting it often lags in time.? This report is right on the heels of the USP report where they clearly state “Patient access to needed drugs can mean the difference between life and death”, access the USP report here.

Why this is important: Well folks it ain’t getting any better.?

June 2024

RFID Utilization

(article link) “RFID adoption is becoming increasingly straightforward with a growing number of manufacturers and 503B outsourced vendors now offering pre-tagged inventory to support these efforts.”

Why this is important: As more and more drugs are tagged with RFID, what do you do with it?? You paid for this extra nicety, but how can you leverage its use?? More to come on this topic for sure.

May 2024