483 #6 – Cross-Contamination

The learning objectives for this week’s 483:

1. Discuss the engineering control requirements for handling and compounding with hazardous drugs
2. List two agents that can be used to deactivate hazardous drugs
3. Discuss the 4 steps required to properly remove hazardous drugs from surfaces and equipment

In this week’s 483 we’re going to look at the importance of cleaning work and non-work surfaces to prevent cross-contamination. What’s interesting about this particular 483 is that the FDA doesn’t note this on sterile products, but an operation’s non-sterile compounding areas. Also, the 483 specifically mentions “hazardous drugs,” so there should be no question in your mind whether the FDA is looking for some compliance with USP Chapter <800>.

Let’s take a look at the observation:

There’s quite a bit of information packed into this short paragraph. First, the 483 mentions that drugs are produced without providing adequate containment. This suggests that perhaps the firm wasn’t using containment ventilated enclosures or powder hoods while compounding. They are also cited for having non-dedicated utensils and equipment for compounding with hazardous drugs. The hazardous drug in this case being tretinoin.

USP <800> specifically talks about non-sterile compounding and the requirements that must be followed:

The C-PECs used for manipulation of nonsterile HDs must be either externally vented (preferred) or have redundant–HEPA filters in series.

USP Chapter <800> Non-sterile Compounding

This table, taken directly from USP <800>, gives the required engineering controls for when you’re compounding with hazardous drugs. First, HDs should be inside an externally vented room or secondary engineering control that has at least 12 air changes per hour and a negative pressure between -0.01 and -0.03 inches water column. Also, the compounding must be performed inside an externally vented primary engineering control or it must have redundant-HEPA filters in series.

Next, let’s talk about the use of dedicated equipment and utensils. If you’re compounding with hazardous drugs, all of the materials and equipment you use should be dedicated specifically for HDs and not be used for non-HD compounding. USP mentions this specifically here:

Disposable or clean equipment for compounding (such as mortars and pestles, and spatulas) must be dedicated for use with HDs.

USP Chapter <800> 13. Compounding

Above this paragraph in <800> it also mentions:

Clean equipment should be dedicated for use with HDs and should be decontaminated after every use.

USP Chapter <800> 12. Dispensing Final Dosage Forms

Even the 483 talks about cleaning utensils, specifically citing that,

…you do not use deactivating agents for the removal of hazardous ingredients on shared utensils.

FDA 483

What agents specifically is the agency talking about when they mention the term “deactivating agent”? A deactivating agent is one that renders the hazardous drug or residue inert. The specific agents that deactivate HDs are oxidizing agents, such as peroxide formulations or sodium hypochlorite.

Here’s another table from USP <800> that talks about all of the steps that need to take place to properly deactivate, decontaminate, clean and disinfect items or surfaces that may have come in contact with hazardous drugs.

So this applies not just to your surfaces that you’ve potentially contaminated with hazardous drugs, but any of the equipment and utensils used as well. While the FDA may not specifically cite you for something where they quote directly out of USP <800> they’re still concerned with cross-contamination between products. Even trace amounts of hazardous drugs in other formulations is just not acceptable.

If you’d like a more in-depth post on the procedure specifically for cleaning up a hazardous drug spill I’d recommend check this post out.

I also made a video that visually details the steps:

https://vimeo.com/424310980

About the author:

Seth DePasquale is a Board Certified Sterile Compounding pharmacist and former co-owner of BET Pharm, LLC in Lexington, KY; a compounding pharmacy specializing in long-acting injectable hormone formulations for equine reproduction. Seth is a 2002 graduate of Albany College of Pharmacy in Albany, NY and is a Registered Pharmacist in New York, Kentucky, Michigan, Oklahoma, Texas, West Virginia, Virginia, Alabama, Tennessee, Mississippi, Arkansas, Nebraska, Louisiana and Oregon.

Contact Seth: seth@lyceumce.com