This goes beyond preparation and administration all the way through packaging, transportation and disposal.

Because USP <800> carries a potentially heavy burden in costs, this resolution has not been met with popular support.¹ But more than 264 drugs are classified as hazardous by NIOSH,² which means that the issue of USP <800> still needs to be carefully considered by every facility that handles these drugs, regardless of enforcement.

The Difference Between USP <797> and <800>

Published in 2004, USP <797> focused on patient safety in sterile compounding pharmacies. Many stakeholders across the industry quietly resented the regulation and some discouraged its discussion. But in 2012, 64 people died and 800 were injured by substandard aseptic compounding practices by a single facility—the New England Compounding Pharmacy. This engendered a sea change of attitude and USP <797> enforcement.³

USP <800>, on the other hand, focuses on a far narrower population and pharmaceutical focus—healthcare professionals and best practices for handling HDs. Bearing in mind that the consequences of HD exposure typically manifest in the long term and are far more difficult to attribute with certainty, there is a lack of urgency behind USP <800> and many feel its burdens exceed the benefits.

What Does USP <800> Entail?

From a broad perspective, an overhaul of the engineering controls for preparing, packaging and unpacking HDs. For example, facilities may continue to use biological safety cabinets (BSCs) and compounding aseptic containment isolators (CACIs) for preparing HDs, but permissible conditions will change.^{4, 5} The “low volume exception” that allowed a Class II BSC or CACI to be used for both sterile and non-sterile HD prep will be eliminated, requiring a dedicated control. More importantly in terms of infrastructure, HD preparation must occur in a negative pressure environment. This necessitates building either an ISO cleanroom or a containment segregated compounding area (C-SCA) with exterior ventilation and strict air change requirements.⁶

It will also require a far more disciplined approach for training the personnel involved with HDs. Employers will have to provide all the appropriate HD safety training for each employee’s position with yearly reassessments and documentation of competency. Additionally, facilities will need to designate a supervisor for HD practices and create a detailed quality assurance program. .⁷

Why USP <800> Makes Sense

It is true that USP <800> will likely not provide safeguards against a dramatic, made-for-TV tragedy like the meningitis outbreak of 2012. But it will help protect healthcare organizations involved with HDs and their employees.

A study in 1999 prompted today’s HD regulations when it showed that women who handled HDs while pregnant had a 40% higher risk for catastrophic pregnancy outcomes.⁸ Current studies have proven that even under existing regulations, healthcare workers who handle antineoplastic drugs in the workplace are significantly more likely to suffer genetic abnormalities than those who do not.^{9, 10, 11}

Considering that Johnson & Johnson was ordered to pay $4.69 billion to 22 women who allegedly developed ovarian cancer from its famous baby powder,¹² protecting the 8 million healthcare workers who handle HDs is in everyone’s best interest.¹³

What Is the Status of Enforcement After December 1, 2019?

That depends on the facility. If it accepts Medicaid and Medicare funding then it is obligated to follow all USP chapters under <1,000>, which will include USP <800>.¹⁴ But the FDA has not formally adopted USP <800> standards, so it won’t be federally mandated—at least in the beginning.

Otherwise, it depends on the state pharmacy board. Although many have chosen to pass on enforcing USP <800> compliance, that doesn’t mean you shouldn’t adopt the standards. In fact, it is much safer for facilities to do so regardless of applicable enforcement.

Why You Shouldn’t Wait to Adopt USP <800> Even Though It Isn’t Required Right Now

First, it will help protect your staff from hazards and safeguard your organization from future legal liabilities. There is a proven HD safety gap in the industry. According to OSHA, 9-13% of pharmacists and nurses who handle HDs never received specialized safety training. Even more troubling, staff members who prepare HDs reportedly fail to wear basic protective equipment such as gowns up to 36% of the time.^{15, 16} Secondly, USP <800> will require significant changes to the engineering controls of many facilities. Some may even need to undertake major infrastructure upgrades. Having as much lead time as possible will be key to making these improvements without derailing operations.

From a human perspective, protecting your employees from cancer, genetic defects and other job-related maladies is a moral imperative. The dangers from prolonged HD exposure, in particular, antineoplastic drugs, is scientifically proven.

From a business perspective, predicting changes in your industry and acting before you are forced to react is the best way to get ahead. Adopting USP <800> standards in advance may offer a competitive advantage over competitors who do not.

From facility infrastructure to operating procedures with hazardous drugs (HDs), USP <800> requires organizations to make significant changes for the sake of HD safety.

HDs pose serious carcinogenic and teratogenic health risks. Even if your facility is not presently required to be USP <800> compliant, regulations can always change, and there are ample moral and legal reasons to do so regardless of enforcement.

The following overview illustrates four major steps you will need to take for USP <800> compliance – and they are simply an introduction. As you will see, each step involves operational and infrastructural challenges that may require considerable research and resources to overcome.

Step 1: List The Hazardous Drugs at Your Facility

Compiling and maintaining a list of HDs at your facility is mandatory for compliance, and it can help form the basis of an introductory risk assessment. More than 264 drugs are classified as hazardous by the National Institute for Occupational Safety and Health (NIOSH).¹⁷ These drugs are grouped into three categories that may require different safe-handling procedures:^18,19

Group 1:

Antineoplastic drugs

Group 2:

Non-antineoplastic drugs that meet HD criteria

Group 3:

Drugs that pose reproductive risk

Each of these drugs has one or more of the following characteristics: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity, organ toxicity at low doses, genotoxicity, or new drugs that mimic existing HDs.

Pay close attention to the risk categories and the dosage forms of the HDs at your facility. High-risk HDs may require engineering controls under USP <800> that your facility does not possess. Certain tablets and capsules that are kept intact may not require the same stringent protocols as injectables, but they may need their own safety strategies.

With this information, compare your current practices for the HDs at your facility to the guidelines set forth in USP <800> for HD safe handling. Add new dosage forms and drugs to this list and review at least once every year. If you’re unsure of the HD status of a new drug, err on the side of caution and consider it to be an HD until you can definitively confirm otherwise.²⁰

Step 2: Examine Receipt, Unpacking and Storage

This is the first area where facilities may need to make significant infrastructure upgrades. Antineoplastic HDs cannot be received and unpacked in a positive pressure environment, which would allow critical cleaning to outside areas in the event of breakage or spills. Instead, a neutral or negative pressure environment must be used.²¹

Storage for most drug forms is affected as well. The majority of HDs, with the exception of some capsules and tablets, must be kept in a negative pressure room with a minimum of 12 air changes per hour (ACPH).²² HDs and non-hazardous drugs cannot share the same refrigerators, and refrigerators for HDs must also be kept in an externally ventilated negative pressure room with the same requirement of 12 ACPH.²³

Step 3: Analyze Engineering Controls For HD Compounding
New engineering controls for HD compounding may be the most difficult and costly upgrades that facilities will have to make for USP <800> compliance. Note that guidelines for non-sterile compounding in USP <795> and sterile compounding in USP <797> must still be followed.²⁴

Containment Primary Engineering Controls (C-PECs):

Under USP <800>, HD compounding requires highly controlled ventilation to protect against harmful byproducts such as aerosols and sprays. Containment primary engineering controls (C-PECs) provide the critical airflow for environmental and occupational protection when compounding HDs. As USP <800> offers general guidelines, facilities have a degree of choice in their controls.

Biological Safety Cabinets (BSCs):

USP <800> lists a range of BSCs that are appropriate for either non-sterile or sterile HD compounding. If your facility already possess BSCs that you would like to use for HD compounding, it is important to verify that they are an approved type for USP <800> compliance.²⁵ If you need new BSCs, allow significant lead time as they require NSF International/American National Standard design verification and field testing.²⁶

Compounding Aseptic Containment Isolators (CACIs):

CACIs come in a variety of configurations and have certain advantageous qualities. From a safety standpoint, they completely isolate the HD from the operator and the environment. From an operational standpoint, they do not require the same level of verification and field testing as BSCs, but rely on testing standards generated by the CACI manufacturer.²⁷

Containment Secondary Engineering Controls for HD Compounding:

Containment secondary engineering controls (C-SECs) are the rooms in which C-PECs reside. C-SECs maintain negative pressure to capture airborne particles from HDs and are essential to C-PEC functionality. As with C-PECs, USP <800> offers a degree of choice in C-SECs for your facility.

Cleanrooms:

An externally vented ISO Class 7 buffer room with an ISO Class 7 ante-room is arguably the most comprehensive solution. Negative pressure requirements between 0.01 and 0.03 inches of water column and 30 ACPH help ensure comprehensive critical cleaning control.²⁸ The two main drawbacks are cost and available facility space.

Containment Segregated Compounding Areas (C-SCAs):

An externally vented C-SCA with a minimum of 12 ACPH is a more economical and easier to implement option for many facilities. C-SCAs do not need to meet ISO standards or need to deliver ISO 7 quality air for medium and low-risk HDs. A drawback is that sterile product beyond use dating (BUD) is limited to 12 hours, which may be shorter than if the HD was prepared in a cleanroom.²⁹

Containment Supplemental Engineering Controls:

These tools generally refer to closed system drug-transfer devices (CSTDs) that offer additional protection in compounding and administering HDs. USP <800> is careful to mention that there is currently not a “published universal performance standard for evaluation of CSTD containment” and cautions facilities to use independent, peer-reviewed studies to guide CSTD selection.³⁰ Regardless of the CSTD you choose, it must be used in conjunction with proper C-PECs, not in place of them.

STEP 4: Devise a Comprehensive Training Program

Under USP <800>, all personnel involved with HDs must be comprehensively trained in safe handling practices that relate to their job function, from receipt through disposal. As outlined by USP <800>, training must include:³¹

• The facility’s list of HDs and corresponding risks
• Standard operating procedures (SOPs) for handling HDs
• Use of personal protective equipment (PPE)
• Use of equipment and devices (such as CSTDs)
• Response to HD exposure – known or suspected
• Managing spills
• HD and critical cleaning material disposal

Employees must prove competency in the above before independent HD handling. Their competency must be reviewed and reassessed every 12 months. Facilities should also designate a supervisor for HD practices and create a detailed quality assurance program.³²

In practical terms, facilities can benefit from creating a standardized HD training program that ensures all SOPs are aligned with USP <800>. Special attention should be paid to training on personal protective equipment (PPE). According to OSHA, staff members who prepare HDs reportedly fail to wear basic protective equipment such as gowns up to 36% of the time.³³

GET ON THE PATH TO HD SAFETY

This brief overview was meant to provide motivation and guidance for becoming USP <800> compliant as expediently as possible, regardless of initial enforcement by your state pharmacy board.

Due to the complexity of challenges posed for many facilities, having as much lead time as possible for USP <800> compliance will be critical to avoiding disruption to operations should regulations change in the future.

If you are conducting a gap analysis, determining cleaning protocols for new engineering controls, or investigating sampling and quality control programs, contact FG Clean Wipes. With nearly 50 years in critical cleaning, we have experience with numerous facilities that meet USP <800> standards. We can help you get up to speed.