Healthcare providers comprise a variety of entities with different scopes of service, all focused on providing care to patients. Hospital and other complex healthcare settings require well-designed mechanical, electrical, and communications systems. And, because hospitals accommodate patients, healthcare professionals, visitors, and other types of stakeholders, they must comply with varying regulations and codes. 

One of the most highly regulated environments in the hospital is the pharmacy — most specifically, the sterile compounding area where production of compounded sterile preparations (CSPs) is performed. With the ever-changing sterile compounding compliance legislation for pharmacies and hospitals, the pressure is now on top of pharmacy professionals to address full regulatory compliance, which requires profound technical and regulatory expertise.

Standards for appropriate procedures and requirements for hospitals that produce compounded sterile preparations are set by the United States Pharmacopeia (USP), a compendium of drug information published annually by the United States Pharmacopeia Convention, a nonprofit organization. USP develops standards for preparing compounded sterile drugs to help ensure patient benefit and reduce risks such as contamination, infection, or incorrect dosing.

Guidelines govern both the sterile compounding process and the compounding pharmacy environment, including cleanrooms. USP Chapter <797>, which became effective on Jan. 1, 2004, was the first enforceable standard for compounded sterile preparations (CSPs).

USP General Chapter <797> Pharmaceutical Compounding — Sterile Preparations is a comprehensive regulation that applies to healthcare institutions, pharmacies, and other facilities in which compounded sterile preparations are prepared, stored, and dispensed. Its purpose is the prevention of infections in patients using pharmaceutical products, as well as the protection of pharmacy staff members who may be exposed to pharmaceutical products. USP <797> includes requirements for personnel, training, facilities, environmental monitoring, storage, and testing of completed preparations. Failure to comply with USP <797> introduces significant risk of harm to patients due to chemical or microbial contamination and/or physical contaminants.

Sterile compounding is one of the highest risk areas of the pharmacy practice. Dust and other low-level environmental pollutants, such as airborne microbes, aerosol particles, and chemical vapors must be tightly controlled.

Cleanrooms have meticulous levels of contamination (ISO Class) specified by the number of particles per cubic meter at a specified particle size. Air entering a cleanroom from the outside must be filtered to exclude dust. The air inside a cleanroom must be constantly recirculated through high-efficiency particulate air (HEPA) filters to control contaminants that are generated inside the room. Particle levels are tested using a particle counter and microorganisms are detected and counted using environmental monitoring methods. 

USP <797> facility/engineering cleanroom guidelines delineate the need for modern cleanroom environments that include the installation of HEPA filters in ceiling fans, the replacement of non-compliant ceiling tiles with cleanroom grade tiles, and the replacement of floors with seamless vinyl flooring.

Further, the need for quality control guidelines and regulations to protect healthcare personnel from possible negative acute and chronic health effects of exposure to hazardous drugs has been a concern for many years. USP developed standards for handling hazardous drugs to increase awareness, provide guidance, and reduce risks to patients and healthcare personnel. These standards, USP General Chapter <800> Hazardous Drugs — Handling in Healthcare Settings, which were originally published in PF 40(3) [May-Jun. 2014], provide standards to protect personnel and the environment when handling hazardous drugs and apply to all healthcare personnel who receive, prepare, administer, transport, or otherwise come in contact with hazardous drugs, as well as all environments in which they are handled. It describes responsibilities of personnel handling hazardous drugs, facility and engineering controls, procedures for deactivating, decontaminating and cleaning, spill control, and documentation. Significant changes will be required for compliance with USP <800>, including training, environment, and policies and procedures, but they are essential to achieve long-needed improvements to patient care and caregiver protection. 

USP has announced its intent to postpone the official date of General Chapter <800> Hazardous Drugs — Handling in Healthcare Settings. Per USP, the intent of this postponement is to align the official date of General Chapter <800> with the official date of the next revision of General Chapter <797> Pharmaceutical Compounding — Sterile Preparations, to provide a unified approach to quality compounding. The next revision to General Chapter <797> is anticipated to be published in the Pharmacopeial Forum 44(5) September-October 2018 for a second round of public comment and is expected to become official on Dec. 1, 2019. Sections of the revised <797> may have longer implementation dates that will allow time for adoption of the standard.

However, these postponements should not give any stakeholder reason to delay; misuse and mishandling of hazardous and sterile compounds are happening every day across the country and placing personnel and patients at risk.

USP <797> stimulated an increase in hospital pharmacy cleanroom installations and renovations, but many cleanrooms in hospitals across the country remain out of compliance due to aging infrastructure, lack of space, poor design criteria, and the introduction of the new requirements in USP <800>. Both chapters are motivating ongoing interest in new cleanroom installations and/or significant renovations to existing cleanrooms.

However, designing and building a cleanroom can be challenging on many levels. Continued operation is essential to patient care and the financial well-being of the hospital — but construction is a dirty job, and cleanroom environments must be protected and continuously monitored.

A fully compliant compounding pharmacy program starts with an adequate environmental analysis and the proper design and construction of primary engineering controls. Fortunately, advances in technology are enabling hospital pharmacy stakeholders to achieve compliance even as their cleanrooms undergo renovation, relocation, or a complete rebuilding.

Air decontamination units with HEPA filters are available that offer an additional and validated unique technology to destroy a full spectrum of airborne microorganisms. These technologies can significantly augment the effectiveness of existing cleanrooms and segregated compounding areas, as well as serve as air quality control mechanisms in temporary cleanrooms during pharmacy renovations.

Pharmacies must continue to build safer environments for medication preparation for both patients and personnel. Advances in air quality control, workflow management software, IV robotic compounding technology, and advanced cleanroom walls, ceilings, and flooring have shown the ability to provide a new standard in aseptic compounding. 

Consideration must also be given to cleanroom features such as nonporous and smooth surfaces, including walls and ceilings that can withstand routine decontamination; proper pressure differentials between rooms, the most positive pressure being in the aseptic processing rooms or areas; use of unidirectional airflow in the immediate vicinity of exposed product or components; sufficient air change frequency; appropriate humidity and temperature environmental controls; and a documented sanitization program.

In the U.S., there are advanced technologies now available that combine different solutions to help control air and surface contamination in hospitals.

These technologies use advanced HEPA filtration quality and microbial destruction using cold plasma without releasing toxic compounds (air decontamination) and/or filtration technology to diffuse a dry and cold hydrogen peroxide and peracetic acid solution to destroy bacteria, spores, fungi and yeasts, viruses, and mycobacteria, including tubercle bacillus, the myobacterium that causes tuberculosis (surface decontamination).

In addition to careful consideration of filtration and decontamination technology, stakeholders should select suppliers, architects, and consultants as they plan new cleanroom environments and/or pharmacy renovations to achieve USP <797> and USP <800> compliance.

Workflow analysis, facility assessments, gap analyses, and reviews of pharmacy operations that include USP <797> and USP <800> survey feedback and analysis report are needed.

Design and installation of advanced monitoring systems for control of non-viable particle count, temperature, humidity, and pressure are also highly recommended.

Experts in cleanroom floor plan and ceiling design, cleanroom air balance analysis, including required Cubic Feet per Minute (CFM) per room (supply/return/exhaust), Air Changes per Hour (ACH) per room, and other environmental requirements should be employed. Guidance and support to help ensure certification and compliance, structural calculations, and drawings needed for Office of Statewide Health Planning and Development (OSHPD) submissions are invaluable.

Because continued operation of cleanrooms in hospital pharmacies is essential, even during renovation and construction activities, companies with the adequate expertise and technologies to enable the use of advanced systems that can significantly augment the effectiveness of existing cleanrooms and segregated compounding areas, as well as serve as air quality control mechanisms to create fully compliant and financially affordable temporary cleanrooms during pharmacy renovations are essential to staff and patient safety, product quality, and operational efficiencies.

References

• http://www.usp.org/products/usp-compounding-compendium
• http://www.ismp.org/tools/guidelines/IVSummit/IVCGuidelines.pdf
• https://www.pppmag.com/article/2035
• http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare

Kim Zurawski began a 30-year career in healthcare marketing in hospital planning at Steris Corp. She has held strategic and product management leadership positions in large, publicly-traded corporations and small, early stage privately-funded enterprises. She has worked for Grifols for two years. 

Juan Miguel Cana Lopez has developed and deployed products, created marketing and sales strategies and provided business leadership in both the U.S. and Europe. Juan started his career with Grifols in 1991. In 1999, he moved to Barcelona to become the country leader of the Hospital Logistics Sales Division. In 2009, Juan moved to the U.S. to lead the newly created Grifols Hospital Division business unit in the North American market. www.grifols.com