Frequently Asked Questions

Modular Cleanroom Manufacturing for Hospital Pharmacies

What is a Pharmacy Cleanroom?

A Pharmacy Cleanroom is an enclosed area in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class

Hospital pharmacy sterile compounding cleanrooms (ie, iv rooms) provide controlled environmental conditions to manufacture Compounded Sterile Products (CSPs) safely and mitigate risks of contamination

503A Facilities: CSPs produced by 503A hospital pharmacies are regulated by USP guidelines requiring that CSPs are processed in a sterile environment with specific levels of cleanliness

For maximum Beyond Use Dating (BUD) The United States Pharmacopoeia (USP) chapter <797> requires that Primary Engineering Controls (PECs, ie hoods) are maintained at International Organization for Standardization (ISO) Class 5 level for 0.5-μm and larger particles. The PECs shall be located within Secondary Engineering Controls (SECs, ie, buffer rooms) maintained at ISO Class 7, and accessed via ante rooms maintained at ISO Class 8 (ISO Class 7 if connected to a negative pressure hazardous drug buffer room).

503B Facilities: Pharmacies that compound products without a patient prescription are considered outsourced facilities and should register with the FDA as 503B pharmacies. 503B pharmacy cleanrooms are regulated by cGMP guidelines and typically require more strictly controlled cleanliness. Brand to provide the definition of the acronym cGMP

Why is mitigating risk of contamination for CSPs so important?

Microbiological contamination in a CSP because of a compromised environment caused by surface or airborne contamination carries a high risk of patient adverse events and mortality

As an example, in 2012 a compounding center distributed contaminated doses due to poor environmental conditions where 798 people with conditions. Seven hundred ninety-eight people contracted meningitis which led to resulted in the deaths of more than 100 people

CSPs are typically injected intravenously, bypassing surface and digestive immune organs and entering directly into the bloodstream. Other parenteral routes, inhalations, and ocular products are also considered CSPs

What is a Modular Cleanroom?

This system enables hospitals to reduce or expand footprint without going through a major demolition project

Modular cleanrooms utilize durable materials that are easy to clean and maintain

Modular cleanrooms typically outperform traditional construction because:

  • They do not include traditional construction materials (eg, wood, drywall)
  • Traditional construction materials can be hydroscopic (possible water collection for mold growth), shed (particulate generation), and break down with regular cleaning with corrosive solutions utilized to kill microorganisms and decontaminate drug residue
  • Traditional construction requires epoxy coatings which require reapplication and cleanroom recertification over time

What are the benefits of Hospital Pharmacy Modular Cleanrooms versus traditional ‘stick-built’ construction?

  • Faster to build with factory fabricated paneling systems delivered onsite
  • Less invasive than conventional construction. Prefabrication of cleanroom panels done off-site to minimize down time and avoid construction delay by others
  • Offers flexibility in cleanroom customization for current and future state
  • The cost of ownership with modular cleanroom systems outperforms conventional construction because of the materials used
  • More durable materials with antimicrobial surfaces that are resistant to UV light degradation and corrosive cleaning solutions typically used in cleanrooms (eg, disinfectants and sporicidal agents)
  • Flush-seamed panels that are cold-welded to keep out any water, microbes, or other contamination from interstitial spaces
  • Ceilings are walkable, allowing for maintenance or repair to Mechanical (HVAC), Electrical, and Plumbing systems (MEP) without having to gain access from inside the cleanroom. This eliminates the need to recertify during maintenance or repair of MEP
  • Windows, doors, lights, and HEPA filters are flush-seamed, easing cleaning and reducing sites for contamination to accumulate
  • Flooring is coved up to flush wall-seams for easy cleaning

How long does it take to build an inclusiv Grifols Cleanroom?

The time it takes to build a cleanroom depends on multiple variables such as the complexity of design, level of internal support for certain aspects, and size of the cleanroom. Based on these variables, cleanrooms can be built within 3-6 months

How can I ensure that my Cleanroom will pass certification per USP <797>?

Grifols guarantees that all our Cleanrooms will pass Controlled Environment Testing Association (CETA) certification

What are the main things to consider when designing and building a Cleanroom?

  • Collaborate with pharmacy leadership and pharmacy operations to identify current and future needs of pharmacy practice and workflow. Types of doses: patient specific, anticipatory batching, TPN, HD and non-HD, nonsterile HD, gene therapy, viral vectors, volume of CSPs; staffing levels; hours of operation; and clinical areas that will be supported: OR, ED, outpatient clinic, inpatient
  • Determine the area where the cleanroom will be installed, preferably adjacent to or near the pharmacy. Hazardous compounding cleanroom location should take into consideration the recommendation and future requirement to exhaust high air volumes out of the building
  • Formulate a transition strategy that will allow continuous support of the hospital. This strategy may include a temporary cleanroom in an existing space or outside the building
  • Determine if a cGMP design and process is desired or whether a standard USP compliant design is sufficient
  • Consider utilizing HEPA-filtered pass-throughs to improve workflow and reduce personnel traffic in the classified spaces while minimizing impact to cleanroom air quality
  • Maintain frequent communications with the Pharmacy and Facilities Engineering Teams during the design and build process
  • Determine whether IV workflow and/or automation will be used

How much does a Hospital Pharmacy Modular Cleanroom cost?

The quoted cost of a cleanroom can range from $150 to $1,000 per sqft, variability is due to the level of complexity required in the build. Beware of low quotes which may reflect inadequate experience or materials and lead to time and cost overruns, inefficient workspaces, and even a need to redesign and rebuild to achieve certification

Should environmental conditions be monitored and recorded?

USP <797>, as of 2020, requires continuous monitoring or daily review and recording of differential pressure

  • Storage areas are considered controlled temperature areas
  • <797> requires continuous monitoring or daily review and recording of the temperature of these spaces with a National Institute of Standards and Technology (NIST) calibrated thermometer
  • Notably, if continuous monitoring is not used, <797> requires review and recording of the storage temperature when placing product into or removing product from the storage unit in order to monitor any temperature aberrations. Because of this requirement, continuous monitoring with excursion alerts is much more efficient. With continuous monitoring, compounding personnel must check only once daily that the monitor’s temperature agrees with a NIST calibrated thermometer

What kind of environmental monitoring is offered?

Grifols offers advanced continuous monitoring intended to provide regulatory reporting in compliance with USP, other enforceable regulations, and best practices. Monitored parameters include:

  • Differential pressures
  • Room and device temperatures
  • Humidity
  • Particle counts

The web-based system allows for remote access and trends analytics helpful for troubleshooting. It can send alerts to pagers, email, or text message devices to notify staff and leadership of excursions from standard, customizable setpoints

What standards of airflow and HVAC should be applied to a Hospital Pharmacy or 503B Cleanroom?

Grifols has more than 2 million square feet of FDA regulated cGMP (Current Good Manufacturing Practice) cleanrooms, and 75 years of experience with the highest levels of safety and quality. Grifols Engineering will apply the same high level of design performance used in our pharma manufacturing environments to our hospital customers. While standards for ISO Class 8 requires a minimum of 20 Air Changes per Hour (ACH or ACPH) and ISO Class 7 requires a minimum of 30 ACH, Grifols Engineering typically exceeds these requirements based on many factors, including:

  • Layout of the room
  • Activity level
  • Equipment placement and airflow
  • Placement of low air returns
  • HEPA filter placement

Grifols Engineers will determine the best possible air flow designs to achieve long term compliance with USP and other regulations for differential pressures, temperature, and humidity. A ‘one-size-fits-all’ approach to designing airflow and HVAC often leads to costly mistakes. Grifols Engineering will consider all factors and apply 75 years of pharma manufacturing experience for the highest levels of performance, efficiency, and longevity.

What are the differences between 503A & 503B facilities?

503A facilities are referred to by the FDA as traditional compounding pharmacies. They must compound in accordance with patient specific prescriptions and are required by the FDA and state boards of pharmacy to comply with USP general chapters up to <999> and other regulations

503B facilities are referred to as outsourcing facilities. They may produce large batches of compounded products—with or without prescriptions—to be sold to healthcare facilities for office use only. 503B facilities are required to have every process validated, whereas 503A facilities are not. This guarantees that all 503B compounded batches meet FDA and cGMP standards

Grifols is an expert in both facility types due to our history of designing, building, and operating many compounding and manufacturing cleanrooms in the US and around the world.

How have Hospital Cleanroom design principals changed?

Conventional healthcare facilities construction has changed in the last decade, with a dramatic shift in the last 5 years. Designing a sterile compounding area based on mechanical and space limitations with minimal end user input has fallen out of favor with current design standards for cleanrooms. Grifols adheres to the standards of compliance with a focus on product movement within the space, staff workflow, movement of air, and long term operational sustainability

Outdated designs allowed for an abundance of supply and drugs to be stored in the buffer and anterooms, where finished doses are passed out of the buffer by staff through the anteroom. The goal was for compounding technicians and pharmacists to gather supply and ingredients faster without leaving the buffer room. However, supply is the second most likely source of contamination (after staff) in a properly operating cleanroom. Reducing supply and limiting staff access by using HEPA filtered pass-throughs allows for access of supply and ingredients between classified and unclassified spaces, which results in less burden of contamination and more efficient workflow. ISO classified storage rooms, separate from anterooms used for staff movement and garbing, can increase the efficiency of supply and drug collection while minimizing risk of contamination

Grifols also offers expert cGMP designs, consulting, and construction for 503B pharmacies, drug manufacturers, and large high volume 503A pharmacies

How often must a Pharmacy Cleanroom be recertified?

ISO classified rooms, facilities, and equipment must be recertified every 6 months by a qualified individual such as a CETA certified technician for ISO classification and a manufacturer's service technician for equipment

How often must a Pharmacy Cleanroom be disinfected?

PECs must be cleaned and disinfected each shift before compounding, before each batch preparation, every 30 minutes during continuous compounding periods, when there are spills, and when contamination is known or suspected due to errors

Task management software can ease recording and reporting without introducing particulate generating paper to the classified spaces. Robotic automation can increase efficiency through daily automated cleaning cycles and manufacturer certification to avoid the interim cleanings except those due to spills or errors

Buffer room and anteroom work surfaces and floors must be cleaned at least daily. Well designed cleanrooms minimize difficult to clean internal angles of work surfaces by moveable tables and carts with solid surfaces and by coving permanent internal angles. As floors are cleaned and disinfected by mopping, this daily procedure is made easier by large-radius floor-to-wall coves and smoothly sealed cove-to-wall transitions

Buffer room and anteroom walls, ceilings, and shelving must be cleaned at least monthly. Well designed cleanrooms minimize difficult to clean internal angles of shelving with solid surfaces and by coving permanent internal angles. Wire work surfaces and shelving are very difficult to clean due to the many uncovered internal angles at wire welds. Wall cleaning is simplified with flush or coved window-, door-, and equipment-to-wall transitions. As ceilings are more easily cleaned and disinfected by mopping, this monthly procedure is made easier by large-radius wall-to-ceiling coves, minimal protrusions, flush and sealed light and HEPA fixtures, and flush or coved equipment joints

KIRO® Oncology

What are the fundamental benefits of using automation technology for hazardous drug compounding?

Staff and patient safety, in-process gravimetric control of dosing accuracies, consistent automated verification and traceability, and increased productivity via remote supervision and approval of compounding operations performed in the robot.

What differentiates KIRO Oncology from other pharmacy robotic systems for hazardous drug compounding?

Flexibility via adaptors that accommodate varying sizes and suppliers of consumables and final containers, fully automated self-cleaning system, and productivity gained through the use of 2 robotic arms that work in concert to complete the different compounding operations and 2 peristaltic pumps to assist the robotic arms.

What is the maximum loading capacity of KIRO Oncology?

The loading capacity of KIRO Oncology includes 8 prefilled bags, semi-rigid containers, elastomeric pumps or cassettes, 8 syringes, 12 vials and 10 partially used vials. This loading capacity is optimal to offer versatility in the preparation of individualized treatments and small batches for oncology.

Is it possible to use disposables of different brands?

KIRO Oncology allows the use of materials of different sizes and brands of materials in a single run and throughout the day, providing automatic means of identifying the materials and drugs that are loaded. Many sizes and brands of prefilled or empty bags, pump cassettes, and elastomeric pumps can be accommodated, even with IV lines attached.

Can KIRO Oncology work outside the Cleanroom?

It is recommended that KIRO Oncology be placed in an ISO Class 7 negative-pressure buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products via USP Chapter 797 and 800. KIRO Oncology may be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 800. All critical compounding tasks (withdrawal, injection, reconstitution, capping, waste disposal, storage of unfinished vials) take place when the window/environment is completely closed under negative pressure. During loading and unloading, sash window pulls cleanroom air into recirculation like in a Class II Type A2 biosafety cabinet (BSC).

Does KIRO Oncology operate in a closed environment?

KIRO Oncology is certified as a Class II Type A2 biosafety cabinet (BSC) and is safe for the handling of hazardous medications during cleaning, loading, and unloading of materials when the window of the device is open. All critical compounding tasks (withdrawal, injection, reconstitution, capping, waste disposal, storage of unfinished vials) take place when the window/environment is completely closed under negative pressure.

Can KIRO Oncology run autonomously?

During device operations, KIRO Oncology operates autonomously for at least 50% of the operator’s time, freeing up the operator to prepare materials and complete simple manual preparations.

What is the rate of throughput of KIRO Oncology?

Production throughput depends on pharmacy workflow and preparation types that are directed to KIRO Oncology for compounding. Throughput ranges from approximately 5 preparations per hour (eg, for large elastomeric pumps fully compounded in KIRO Oncology) to approximately 15 preparations per hour to produce syringes in series.

How is the risk of user exposure to hazardous waste mitigated during replacement of the waste disposal containers?

KIRO Oncology’s double-port transfer system waste bags ensure no exposure during assembly and removal of the waste containers, while supporting the use of standard waste containers for the management of hazardous waste.

How is KIRO Oncology cleaned?

KIRO Oncology includes an automated, self-cleaning program. The cleaning process uses sterile water with a disinfectant that facilitates disinfection and chemical decontamination of the compounding area with a 99% efficiency.

How long is the self-cleaning cycle of KIRO Oncology?

The self-cleaning cycle takes about 15 minutes to set up, about 10 of which can be done at any time during the day. The cycle itself takes only about 5 minutes and will dry in less than 3 hours.

How should I dispose of the cleaning process waste?

You should work with your local environmental protection agency (EPA) or department of environmental protection (DEP) office to determine the appropriate waste stream for the cleaning process.

Can KIRO Oncology be used to compound nonhazardous drugs?

KIRO Oncology can be used for preparation of particularly complex nonhazardous preparations. In this application, the device is called KIRO SP and is installed in a positive-pressure ISO 7 buffer room. The installation and operation of KIRO SP are very similar to applications where hazardous drugs are prepared in KIRO Oncology.

Is KIRO Oncology as safe as closed system transfer devices?

The critical compounding steps involving reconstitution, withdrawal, and final container filling happen in an automated manner and in an isolated environment. This ensures that KIRO Oncology is at least as safe as any connector manipulated manually. Moreover, KIRO uses a vented and aerosol-filtering spike for the very critical step of reconstitution, which prevents the generation of overpressure in the reconstituted vial and prevents the release of contaminated aerosols into the compounding area.

Is KIRO Oncology reliable?

As of 2022, the average uptime of KIRO Oncology/SP units being used across the world is 98%.

Will I need to rebalance my Cleanroom air pressure?

KIRO Oncology has an air flow rate between 3500 ft3/h (100 m3/h) and 21000 ft3/h (600m3/h). Customers replacing an existing A2 BSC with KIRO Oncology may not need to rebalance their room.

How does the system avoid a user mixing up final containers?

KIRO Oncology utilizes barcoded tracking labels, barcode scanners, vision systems, gravimetrics, and automated process controls to ensure the identity of drugs, disposables, and final containers. Final labels are printed one-at-a-time only after the CSP is approved in the system when the appropriate tracking label is scanned at the printer.

Is the robot on casters for easy movement?

The system is supported by 7 support legs (not on wheels) for a lower minimum floor load rating than competitors. The system ships with 2 lifters on wheels, which can be stored when not in use.

KIRO® SP

What are the fundamental benefits of using automation technology for pediatric and high-risk drug compounding?

In-process gravimetric control of dosing accuracies, consistent automated verification and traceability, staff and patient safety, and increased productivity via remote supervision and approval of compounding operations performed in the robot.

What differentiates KIRO SP from other pharmacy robotic systems for pediatric and high-risk drug compounding?

Flexibility via adaptors that accommodate varying sizes and suppliers of consumables and final containers, fully automated self-cleaning system, and productivity gained through the use of 2 robotic arms that work in concert to complete the different compounding operations and 2 peristaltic pumps to assist the robotic arms.

What is the maximum loading capacity of KIRO SP?

The loading capacity of KIRO Oncology includes 8 prefilled bags, semi-rigid containers, elastomeric pumps or cassettes, 8 syringes, 12 vials and 10 partially used vials. This loading capacity is optimal to offer versatility in the preparation of individualized treatments and small batches.

Is it possible to use disposables of different brands?

It is recommended that KIRO SP be placed in an ISO Class 7 buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products via USP Chapter 797. KIRO SP may be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 797.

Can KIRO SP work outside the Cleanroom?

It is recommended that KIRO SP be placed in an ISO Class 7 positive-pressure buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products via USP Chapter 797. KIRO SP MAY be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 797.

Does KIRO SP operate in a closed environment?

KIRO SP is certified as a Class II Type A2 biosafety cabinet (BSC) and is safe for the handling of high risk drugs during cleaning, loading, and unloading of materials when the window of the device is open. All critical compounding tasks (withdrawal, injection, reconstitution, capping, waste disposal, storage of unfinished vials) take place when the window/environment is completely closed.

Can KIRO SP run autonomously?

During device operations, KIRO SP operates autonomously for at least 50% of the operator’s time, freeing up the operator to prepare materials and complete simple manual preparations.

What is the rate of throughput of KIRO SP?

Production throughput depends on pharmacy workflow and preparation types that are directed to KIRO SP for compounding. Throughput ranges from approximately 5 preparations per hour (eg, for large elastomeric pumps fully compounded in KIRO SP) to approximately 15 preparations per hour to produce syringes in series.

How is KIRO SP cleaned?

KIRO SP includes an automated, self-cleaning program. The cleaning process uses sterile water with a disinfectant that facilitates sanitizing and chemical decontamination of the compounding area with a 99% efficiency.

How long is the self-cleaning cycle of KIRO SP?

The self-cleaning cycle takes about 15 minutes to set up, about 10 of which can be done at any time during the day. The cycle itself takes only about 5 minutes and will dry in less than 8 hours.

Can KIRO SP be used to compound hazardous drugs?

KIRO SP can be used for preparation of hazardous preparations. In this application, the device is called KIRO Oncology and is installed in a negative-pressure ISO 7 buffer room. The installation and operation of KIRO Oncology are very similar to applications where pediatric and high-risk drugs are prepared in KIRO SP.

Are there any medications that cannot be handled by KIRO SP?

KIRO SP cannot manipulate ampules directly, but if previously transferred into a syringe or vial, ampule drugs and diluents can be used in the robot. Some very specific reconstitutions requiring special considerations, eg, incubation before mixing, are not currently supported. Currently, medications containing more than one drug or diluent cannot be compounded in KIRO SP; however, this is on the roadmap for future development.

Is KIRO SP reliable?

As of 2020, the average uptime of KIRO Oncology/SP units being used across the world is 94%.

Will I need to rebalance my Cleanroom air pressure?

KIRO SP can be vented back into the room to avoid any change to room air pressure. See KIRO Oncology for hazardous preparation.

How does the system avoid a user mixing up final containers?

KIRO SP utilizes barcoded tracking labels, barcode scanners, vision systems, gravimetrics, and automated process controls to ensure the identity of drugs, disposables, and final containers. Final labels are printed one-at-a-time only after the CSP is approved in the system when the appropriate tracking label is scanned at the printer.

Is the robot on casters for easy movement?

The system is supported by 7 support legs (not on wheels) for a lower minimum floor load rating than competitors. The system ships with 2 lifters on wheels, which can be stored when not in use.

KIRO® Fill

Why automate?

Even with proper cleansing and garbing, personnel are the main source of contamination in a properly functioning cleanroom, especially viable microorganisms like skin bacteria, which can cause infection by parenteral routes such as intravenous drug administration. Automation may reduce the risk of contaminated sterile compounded products (CSPs) by performing the most critical tasks in a controlled and validated aseptic environment without human presence.

What is non-hazardous sterile compounding automation?

Non-hazardous sterile compounding automation includes robots, devices, and systems which perform some or all the compounding tasks traditionally done manually by a pharmacist or pharmacy technician. Automation can increase safety, efficiency, documentation, and reporting. These devices and systems must be designed and operated in such a way as to ensure the accountability, accuracy, quality, safety, and uniformity of the final product. However, they can be faster and more efficient than hazardous sterile compounding automation due to the low risk of health and environmental consequences presented by the products they prepare.

Why do we need KIRO Fill?

KIRO Fill helps your pharmacy produce higher volumes of batched CSPs per day, reducing reliance on outsourced compounding. This can reduce costs, alleviate sterility and safety concerns, and give you the flexibility to produce exactly the concentrations and volumes you need, when you need them.

How is KIRO Fill different?

In the world of non-hazardous sterile compounding automation, KIRO Fill is a unique syringe compounding device designed with sensible automation to provide significant throughput for batching of non-hazardous CSPs while delivering proven consistency and dose accuracy.

You can be confident that you are managing costs and maintaining quality to help protect patients and staff.
 

Is KIRO Fill right for us?

It is if you currently, or plan to, produce and/or outsource a combined total of 5,000 or more non-hazardous sterile compounded product syringes per month.

Why is KIRO Fill better than outsourcing?

KIRO Fill production has a lower lead time than ordering from an outsourcer. You can capitalize costs, control your formulary, and maintain control and oversight of the compounding process to ensure the safety of your patients.

Why is KIRO Fill better than manual preparation?

KIRO Fill may reduce repetitive stress and human error. Through KIRO Link, the system provides control and traceability of preparation, detailed compounding records including air quality data, and batch reports.

Why is KIRO Fill better than a repeater pump?

KIRO Fill saves you time because it does not require daily calibration. It may reduce repetitive stress. KIRO Fill is sensible automation for an efficient, controlled, and reliable process. Through KIRO Soft and the inclusiv dashboard, the system provides control and traceability of preparation, detailed compounding records including air quality data, and automated batch reports.

Why is KIRO Fill better than the competition?

KIRO Fill delivers up to 150 syringes per hour! It offers flexible integration and superior documentation. Through KIRO Link, the system provides control and traceability of preparation, detailed compounding records including air quality data, and batch reports. KIRO Fill has fast batch setup, is easy to clean, has high throughput, and low installation costs.

How is KIRO Fill so fast?

KIRO Fill is sensible automation designed to automate the most critical syringe filling tasks: dosing and capping. Two robotic units work in parallel to precisely dose syringes from a source container and apply traceable tamper-evident caps. The unique design of KIRO Fill allows completed syringes to be replaced with empty syringes while others are being filled without waiting for a carousel or door. Watch the KIRO Fill video to see for yourself.

What is the maximum batch size of KIRO Fill?

KIRO Fill can produce batches of up to 100 syringes in less than an hour. Operators are directed by LEDs to know which filled bags and automatically capped syringes they unload from the 20 easily reachable positions in the counter-height ISO 5 horizontal laminar airflow workbench.

Can KIRO Fill work outside the Cleanroom?

It is recommended that KIRO Fill be placed in an ISO Class 7 buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products per USP Chapter 797 or comply with cGMP requirements. KIRO Fill may also be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 797.

Modular Cleanroom Manufacturing for Hospital Pharmacies

What is a Pharmacy Cleanroom?

A Pharmacy Cleanroom is an enclosed area in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class

Hospital pharmacy sterile compounding cleanrooms (ie, iv rooms) provide controlled environmental conditions to manufacture Compounded Sterile Products (CSPs) safely and mitigate risks of contamination

503A Facilities: CSPs produced by 503A hospital pharmacies are regulated by USP guidelines requiring that CSPs are processed in a sterile environment with specific levels of cleanliness

For maximum Beyond Use Dating (BUD) The United States Pharmacopoeia (USP) chapter <797> requires that Primary Engineering Controls (PECs, ie hoods) are maintained at International Organization for Standardization (ISO) Class 5 level for 0.5-μm and larger particles. The PECs shall be located within Secondary Engineering Controls (SECs, ie, buffer rooms) maintained at ISO Class 7, and accessed via ante rooms maintained at ISO Class 8 (ISO Class 7 if connected to a negative pressure hazardous drug buffer room).

503B Facilities: Pharmacies that compound products without a patient prescription are considered outsourced facilities and should register with the FDA as 503B pharmacies. 503B pharmacy cleanrooms are regulated by cGMP guidelines and typically require more strictly controlled cleanliness. Brand to provide the definition of the acronym cGMP

Why is mitigating risk of contamination for CSPs so important?

Microbiological contamination in a CSP because of a compromised environment caused by surface or airborne contamination carries a high risk of patient adverse events and mortality

As an example, in 2012 a compounding center distributed contaminated doses due to poor environmental conditions where 798 people with conditions. Seven hundred ninety-eight people contracted meningitis which led to resulted in the deaths of more than 100 people

CSPs are typically injected intravenously, bypassing surface and digestive immune organs and entering directly into the bloodstream. Other parenteral routes, inhalations, and ocular products are also considered CSPs

What is a Modular Cleanroom?

This system enables hospitals to reduce or expand footprint without going through a major demolition project

Modular cleanrooms utilize durable materials that are easy to clean and maintain

Modular cleanrooms typically outperform traditional construction because:

  • They do not include traditional construction materials (eg, wood, drywall)
  • Traditional construction materials can be hydroscopic (possible water collection for mold growth), shed (particulate generation), and break down with regular cleaning with corrosive solutions utilized to kill microorganisms and decontaminate drug residue
  • Traditional construction requires epoxy coatings which require reapplication and cleanroom recertification over time

What are the benefits of Hospital Pharmacy Modular Cleanrooms versus traditional ‘stick-built’ construction?

  • Faster to build with factory fabricated paneling systems delivered onsite
  • Less invasive than conventional construction. Prefabrication of cleanroom panels done off-site to minimize down time and avoid construction delay by others
  • Offers flexibility in cleanroom customization for current and future state
  • The cost of ownership with modular cleanroom systems outperforms conventional construction because of the materials used
  • More durable materials with antimicrobial surfaces that are resistant to UV light degradation and corrosive cleaning solutions typically used in cleanrooms (eg, disinfectants and sporicidal agents)
  • Flush-seamed panels that are cold-welded to keep out any water, microbes, or other contamination from interstitial spaces
  • Ceilings are walkable, allowing for maintenance or repair to Mechanical (HVAC), Electrical, and Plumbing systems (MEP) without having to gain access from inside the cleanroom. This eliminates the need to recertify during maintenance or repair of MEP
  • Windows, doors, lights, and HEPA filters are flush-seamed, easing cleaning and reducing sites for contamination to accumulate
  • Flooring is coved up to flush wall-seams for easy cleaning

How long does it take to build an inclusiv Grifols Cleanroom?

The time it takes to build a cleanroom depends on multiple variables such as the complexity of design, level of internal support for certain aspects, and size of the cleanroom. Based on these variables, cleanrooms can be built within 3-6 months

How can I ensure that my Cleanroom will pass certification per USP <797>?

Grifols guarantees that all our Cleanrooms will pass Controlled Environment Testing Association (CETA) certification

What are the main things to consider when designing and building a Cleanroom?

  • Collaborate with pharmacy leadership and pharmacy operations to identify current and future needs of pharmacy practice and workflow. Types of doses: patient specific, anticipatory batching, TPN, HD and non-HD, nonsterile HD, gene therapy, viral vectors, volume of CSPs; staffing levels; hours of operation; and clinical areas that will be supported: OR, ED, outpatient clinic, inpatient
  • Determine the area where the cleanroom will be installed, preferably adjacent to or near the pharmacy. Hazardous compounding cleanroom location should take into consideration the recommendation and future requirement to exhaust high air volumes out of the building
  • Formulate a transition strategy that will allow continuous support of the hospital. This strategy may include a temporary cleanroom in an existing space or outside the building
  • Determine if a cGMP design and process is desired or whether a standard USP compliant design is sufficient
  • Consider utilizing HEPA-filtered pass-throughs to improve workflow and reduce personnel traffic in the classified spaces while minimizing impact to cleanroom air quality
  • Maintain frequent communications with the Pharmacy and Facilities Engineering Teams during the design and build process
  • Determine whether IV workflow and/or automation will be used

How much does a Hospital Pharmacy Modular Cleanroom cost?

The quoted cost of a cleanroom can range from $150 to $1,000 per sqft, variability is due to the level of complexity required in the build. Beware of low quotes which may reflect inadequate experience or materials and lead to time and cost overruns, inefficient workspaces, and even a need to redesign and rebuild to achieve certification

Should environmental conditions be monitored and recorded?

USP <797>, as of 2020, requires continuous monitoring or daily review and recording of differential pressure

  • Storage areas are considered controlled temperature areas
  • <797> requires continuous monitoring or daily review and recording of the temperature of these spaces with a National Institute of Standards and Technology (NIST) calibrated thermometer
  • Notably, if continuous monitoring is not used, <797> requires review and recording of the storage temperature when placing product into or removing product from the storage unit in order to monitor any temperature aberrations. Because of this requirement, continuous monitoring with excursion alerts is much more efficient. With continuous monitoring, compounding personnel must check only once daily that the monitor’s temperature agrees with a NIST calibrated thermometer

What kind of environmental monitoring is offered?

Grifols offers advanced continuous monitoring intended to provide regulatory reporting in compliance with USP, other enforceable regulations, and best practices. Monitored parameters include:

  • Differential pressures
  • Room and device temperatures
  • Humidity
  • Particle counts

The web-based system allows for remote access and trends analytics helpful for troubleshooting. It can send alerts to pagers, email, or text message devices to notify staff and leadership of excursions from standard, customizable setpoints

What standards of airflow and HVAC should be applied to a Hospital Pharmacy or 503B Cleanroom?

Grifols has more than 2 million square feet of FDA regulated cGMP (Current Good Manufacturing Practice) cleanrooms, and 75 years of experience with the highest levels of safety and quality. Grifols Engineering will apply the same high level of design performance used in our pharma manufacturing environments to our hospital customers. While standards for ISO Class 8 requires a minimum of 20 Air Changes per Hour (ACH or ACPH) and ISO Class 7 requires a minimum of 30 ACH, Grifols Engineering typically exceeds these requirements based on many factors, including:

  • Layout of the room
  • Activity level
  • Equipment placement and airflow
  • Placement of low air returns
  • HEPA filter placement

Grifols Engineers will determine the best possible air flow designs to achieve long term compliance with USP and other regulations for differential pressures, temperature, and humidity. A ‘one-size-fits-all’ approach to designing airflow and HVAC often leads to costly mistakes. Grifols Engineering will consider all factors and apply 75 years of pharma manufacturing experience for the highest levels of performance, efficiency, and longevity.

What are the differences between 503A & 503B facilities?

503A facilities are referred to by the FDA as traditional compounding pharmacies. They must compound in accordance with patient specific prescriptions and are required by the FDA and state boards of pharmacy to comply with USP general chapters up to <999> and other regulations

503B facilities are referred to as outsourcing facilities. They may produce large batches of compounded products—with or without prescriptions—to be sold to healthcare facilities for office use only. 503B facilities are required to have every process validated, whereas 503A facilities are not. This guarantees that all 503B compounded batches meet FDA and cGMP standards

Grifols is an expert in both facility types due to our history of designing, building, and operating many compounding and manufacturing cleanrooms in the US and around the world.

How have Hospital Cleanroom design principals changed?

Conventional healthcare facilities construction has changed in the last decade, with a dramatic shift in the last 5 years. Designing a sterile compounding area based on mechanical and space limitations with minimal end user input has fallen out of favor with current design standards for cleanrooms. Grifols adheres to the standards of compliance with a focus on product movement within the space, staff workflow, movement of air, and long term operational sustainability

Outdated designs allowed for an abundance of supply and drugs to be stored in the buffer and anterooms, where finished doses are passed out of the buffer by staff through the anteroom. The goal was for compounding technicians and pharmacists to gather supply and ingredients faster without leaving the buffer room. However, supply is the second most likely source of contamination (after staff) in a properly operating cleanroom. Reducing supply and limiting staff access by using HEPA filtered pass-throughs allows for access of supply and ingredients between classified and unclassified spaces, which results in less burden of contamination and more efficient workflow. ISO classified storage rooms, separate from anterooms used for staff movement and garbing, can increase the efficiency of supply and drug collection while minimizing risk of contamination

Grifols also offers expert cGMP designs, consulting, and construction for 503B pharmacies, drug manufacturers, and large high volume 503A pharmacies

How often must a Pharmacy Cleanroom be recertified?

ISO classified rooms, facilities, and equipment must be recertified every 6 months by a qualified individual such as a CETA certified technician for ISO classification and a manufacturer's service technician for equipment

How often must a Pharmacy Cleanroom be disinfected?

PECs must be cleaned and disinfected each shift before compounding, before each batch preparation, every 30 minutes during continuous compounding periods, when there are spills, and when contamination is known or suspected due to errors

Task management software can ease recording and reporting without introducing particulate generating paper to the classified spaces. Robotic automation can increase efficiency through daily automated cleaning cycles and manufacturer certification to avoid the interim cleanings except those due to spills or errors

Buffer room and anteroom work surfaces and floors must be cleaned at least daily. Well designed cleanrooms minimize difficult to clean internal angles of work surfaces by moveable tables and carts with solid surfaces and by coving permanent internal angles. As floors are cleaned and disinfected by mopping, this daily procedure is made easier by large-radius floor-to-wall coves and smoothly sealed cove-to-wall transitions

Buffer room and anteroom walls, ceilings, and shelving must be cleaned at least monthly. Well designed cleanrooms minimize difficult to clean internal angles of shelving with solid surfaces and by coving permanent internal angles. Wire work surfaces and shelving are very difficult to clean due to the many uncovered internal angles at wire welds. Wall cleaning is simplified with flush or coved window-, door-, and equipment-to-wall transitions. As ceilings are more easily cleaned and disinfected by mopping, this monthly procedure is made easier by large-radius wall-to-ceiling coves, minimal protrusions, flush and sealed light and HEPA fixtures, and flush or coved equipment joints

KIRO® Oncology

What are the fundamental benefits of using automation technology for hazardous drug compounding?

Staff and patient safety, in-process gravimetric control of dosing accuracies, consistent automated verification and traceability, and increased productivity via remote supervision and approval of compounding operations performed in the robot.

What differentiates KIRO Oncology from other pharmacy robotic systems for hazardous drug compounding?

Flexibility via adaptors that accommodate varying sizes and suppliers of consumables and final containers, fully automated self-cleaning system, and productivity gained through the use of 2 robotic arms that work in concert to complete the different compounding operations and 2 peristaltic pumps to assist the robotic arms.

What is the maximum loading capacity of KIRO Oncology?

The loading capacity of KIRO Oncology includes 8 prefilled bags, semi-rigid containers, elastomeric pumps or cassettes, 8 syringes, 12 vials and 10 partially used vials. This loading capacity is optimal to offer versatility in the preparation of individualized treatments and small batches for oncology.

Is it possible to use disposables of different brands?

KIRO Oncology allows the use of materials of different sizes and brands of materials in a single run and throughout the day, providing automatic means of identifying the materials and drugs that are loaded. Many sizes and brands of prefilled or empty bags, pump cassettes, and elastomeric pumps can be accommodated, even with IV lines attached.

Can KIRO Oncology work outside the Cleanroom?

It is recommended that KIRO Oncology be placed in an ISO Class 7 negative-pressure buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products via USP Chapter 797 and 800. KIRO Oncology may be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 800. All critical compounding tasks (withdrawal, injection, reconstitution, capping, waste disposal, storage of unfinished vials) take place when the window/environment is completely closed under negative pressure. During loading and unloading, sash window pulls cleanroom air into recirculation like in a Class II Type A2 biosafety cabinet (BSC).

Does KIRO Oncology operate in a closed environment?

KIRO Oncology is certified as a Class II Type A2 biosafety cabinet (BSC) and is safe for the handling of hazardous medications during cleaning, loading, and unloading of materials when the window of the device is open. All critical compounding tasks (withdrawal, injection, reconstitution, capping, waste disposal, storage of unfinished vials) take place when the window/environment is completely closed under negative pressure.

Can KIRO Oncology run autonomously?

During device operations, KIRO Oncology operates autonomously for at least 50% of the operator’s time, freeing up the operator to prepare materials and complete simple manual preparations.

What is the rate of throughput of KIRO Oncology?

Production throughput depends on pharmacy workflow and preparation types that are directed to KIRO Oncology for compounding. Throughput ranges from approximately 5 preparations per hour (eg, for large elastomeric pumps fully compounded in KIRO Oncology) to approximately 15 preparations per hour to produce syringes in series.

How is the risk of user exposure to hazardous waste mitigated during replacement of the waste disposal containers?

KIRO Oncology’s double-port transfer system waste bags ensure no exposure during assembly and removal of the waste containers, while supporting the use of standard waste containers for the management of hazardous waste.

How is KIRO Oncology cleaned?

KIRO Oncology includes an automated, self-cleaning program. The cleaning process uses sterile water with a disinfectant that facilitates disinfection and chemical decontamination of the compounding area with a 99% efficiency.

How long is the self-cleaning cycle of KIRO Oncology?

The self-cleaning cycle takes about 15 minutes to set up, about 10 of which can be done at any time during the day. The cycle itself takes only about 5 minutes and will dry in less than 3 hours.

How should I dispose of the cleaning process waste?

You should work with your local environmental protection agency (EPA) or department of environmental protection (DEP) office to determine the appropriate waste stream for the cleaning process.

Can KIRO Oncology be used to compound nonhazardous drugs?

KIRO Oncology can be used for preparation of particularly complex nonhazardous preparations. In this application, the device is called KIRO SP and is installed in a positive-pressure ISO 7 buffer room. The installation and operation of KIRO SP are very similar to applications where hazardous drugs are prepared in KIRO Oncology.

Is KIRO Oncology as safe as closed system transfer devices?

The critical compounding steps involving reconstitution, withdrawal, and final container filling happen in an automated manner and in an isolated environment. This ensures that KIRO Oncology is at least as safe as any connector manipulated manually. Moreover, KIRO uses a vented and aerosol-filtering spike for the very critical step of reconstitution, which prevents the generation of overpressure in the reconstituted vial and prevents the release of contaminated aerosols into the compounding area.

Is KIRO Oncology reliable?

As of 2022, the average uptime of KIRO Oncology/SP units being used across the world is 98%.

Will I need to rebalance my Cleanroom air pressure?

KIRO Oncology has an air flow rate between 3500 ft3/h (100 m3/h) and 21000 ft3/h (600m3/h). Customers replacing an existing A2 BSC with KIRO Oncology may not need to rebalance their room.

How does the system avoid a user mixing up final containers?

KIRO Oncology utilizes barcoded tracking labels, barcode scanners, vision systems, gravimetrics, and automated process controls to ensure the identity of drugs, disposables, and final containers. Final labels are printed one-at-a-time only after the CSP is approved in the system when the appropriate tracking label is scanned at the printer.

Is the robot on casters for easy movement?

The system is supported by 7 support legs (not on wheels) for a lower minimum floor load rating than competitors. The system ships with 2 lifters on wheels, which can be stored when not in use.

KIRO® SP

What are the fundamental benefits of using automation technology for pediatric and high-risk drug compounding?

In-process gravimetric control of dosing accuracies, consistent automated verification and traceability, staff and patient safety, and increased productivity via remote supervision and approval of compounding operations performed in the robot.

What differentiates KIRO SP from other pharmacy robotic systems for pediatric and high-risk drug compounding?

Flexibility via adaptors that accommodate varying sizes and suppliers of consumables and final containers, fully automated self-cleaning system, and productivity gained through the use of 2 robotic arms that work in concert to complete the different compounding operations and 2 peristaltic pumps to assist the robotic arms.

What is the maximum loading capacity of KIRO SP?

The loading capacity of KIRO Oncology includes 8 prefilled bags, semi-rigid containers, elastomeric pumps or cassettes, 8 syringes, 12 vials and 10 partially used vials. This loading capacity is optimal to offer versatility in the preparation of individualized treatments and small batches.

Is it possible to use disposables of different brands?

It is recommended that KIRO SP be placed in an ISO Class 7 buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products via USP Chapter 797. KIRO SP may be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 797.

Can KIRO SP work outside the Cleanroom?

It is recommended that KIRO SP be placed in an ISO Class 7 positive-pressure buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products via USP Chapter 797. KIRO SP MAY be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 797.

Does KIRO SP operate in a closed environment?

KIRO SP is certified as a Class II Type A2 biosafety cabinet (BSC) and is safe for the handling of high risk drugs during cleaning, loading, and unloading of materials when the window of the device is open. All critical compounding tasks (withdrawal, injection, reconstitution, capping, waste disposal, storage of unfinished vials) take place when the window/environment is completely closed.

Can KIRO SP run autonomously?

During device operations, KIRO SP operates autonomously for at least 50% of the operator’s time, freeing up the operator to prepare materials and complete simple manual preparations.

What is the rate of throughput of KIRO SP?

Production throughput depends on pharmacy workflow and preparation types that are directed to KIRO SP for compounding. Throughput ranges from approximately 5 preparations per hour (eg, for large elastomeric pumps fully compounded in KIRO SP) to approximately 15 preparations per hour to produce syringes in series.

How is KIRO SP cleaned?

KIRO SP includes an automated, self-cleaning program. The cleaning process uses sterile water with a disinfectant that facilitates sanitizing and chemical decontamination of the compounding area with a 99% efficiency.

How long is the self-cleaning cycle of KIRO SP?

The self-cleaning cycle takes about 15 minutes to set up, about 10 of which can be done at any time during the day. The cycle itself takes only about 5 minutes and will dry in less than 8 hours.

Can KIRO SP be used to compound hazardous drugs?

KIRO SP can be used for preparation of hazardous preparations. In this application, the device is called KIRO Oncology and is installed in a negative-pressure ISO 7 buffer room. The installation and operation of KIRO Oncology are very similar to applications where pediatric and high-risk drugs are prepared in KIRO SP.

Are there any medications that cannot be handled by KIRO SP?

KIRO SP cannot manipulate ampules directly, but if previously transferred into a syringe or vial, ampule drugs and diluents can be used in the robot. Some very specific reconstitutions requiring special considerations, eg, incubation before mixing, are not currently supported. Currently, medications containing more than one drug or diluent cannot be compounded in KIRO SP; however, this is on the roadmap for future development.

Is KIRO SP reliable?

As of 2020, the average uptime of KIRO Oncology/SP units being used across the world is 94%.

Will I need to rebalance my Cleanroom air pressure?

KIRO SP can be vented back into the room to avoid any change to room air pressure. See KIRO Oncology for hazardous preparation.

How does the system avoid a user mixing up final containers?

KIRO SP utilizes barcoded tracking labels, barcode scanners, vision systems, gravimetrics, and automated process controls to ensure the identity of drugs, disposables, and final containers. Final labels are printed one-at-a-time only after the CSP is approved in the system when the appropriate tracking label is scanned at the printer.

Is the robot on casters for easy movement?

The system is supported by 7 support legs (not on wheels) for a lower minimum floor load rating than competitors. The system ships with 2 lifters on wheels, which can be stored when not in use.

KIRO® Fill

Why automate?

Even with proper cleansing and garbing, personnel are the main source of contamination in a properly functioning cleanroom, especially viable microorganisms like skin bacteria, which can cause infection by parenteral routes such as intravenous drug administration. Automation may reduce the risk of contaminated sterile compounded products (CSPs) by performing the most critical tasks in a controlled and validated aseptic environment without human presence.

What is non-hazardous sterile compounding automation?

Non-hazardous sterile compounding automation includes robots, devices, and systems which perform some or all the compounding tasks traditionally done manually by a pharmacist or pharmacy technician. Automation can increase safety, efficiency, documentation, and reporting. These devices and systems must be designed and operated in such a way as to ensure the accountability, accuracy, quality, safety, and uniformity of the final product. However, they can be faster and more efficient than hazardous sterile compounding automation due to the low risk of health and environmental consequences presented by the products they prepare.

Why do we need KIRO Fill?

KIRO Fill helps your pharmacy produce higher volumes of batched CSPs per day, reducing reliance on outsourced compounding. This can reduce costs, alleviate sterility and safety concerns, and give you the flexibility to produce exactly the concentrations and volumes you need, when you need them.

How is KIRO Fill different?

In the world of non-hazardous sterile compounding automation, KIRO Fill is a unique syringe compounding device designed with sensible automation to provide significant throughput for batching of non-hazardous CSPs while delivering proven consistency and dose accuracy.

You can be confident that you are managing costs and maintaining quality to help protect patients and staff.
 

Is KIRO Fill right for us?

It is if you currently, or plan to, produce and/or outsource a combined total of 5,000 or more non-hazardous sterile compounded product syringes per month.

Why is KIRO Fill better than outsourcing?

KIRO Fill production has a lower lead time than ordering from an outsourcer. You can capitalize costs, control your formulary, and maintain control and oversight of the compounding process to ensure the safety of your patients.

Why is KIRO Fill better than manual preparation?

KIRO Fill may reduce repetitive stress and human error. Through KIRO Link, the system provides control and traceability of preparation, detailed compounding records including air quality data, and batch reports.

Why is KIRO Fill better than a repeater pump?

KIRO Fill saves you time because it does not require daily calibration. It may reduce repetitive stress. KIRO Fill is sensible automation for an efficient, controlled, and reliable process. Through KIRO Soft and the inclusiv dashboard, the system provides control and traceability of preparation, detailed compounding records including air quality data, and automated batch reports.

Why is KIRO Fill better than the competition?

KIRO Fill delivers up to 150 syringes per hour! It offers flexible integration and superior documentation. Through KIRO Link, the system provides control and traceability of preparation, detailed compounding records including air quality data, and batch reports. KIRO Fill has fast batch setup, is easy to clean, has high throughput, and low installation costs.

How is KIRO Fill so fast?

KIRO Fill is sensible automation designed to automate the most critical syringe filling tasks: dosing and capping. Two robotic units work in parallel to precisely dose syringes from a source container and apply traceable tamper-evident caps. The unique design of KIRO Fill allows completed syringes to be replaced with empty syringes while others are being filled without waiting for a carousel or door. Watch the KIRO Fill video to see for yourself.

What is the maximum batch size of KIRO Fill?

KIRO Fill can produce batches of up to 100 syringes in less than an hour. Operators are directed by LEDs to know which filled bags and automatically capped syringes they unload from the 20 easily reachable positions in the counter-height ISO 5 horizontal laminar airflow workbench.

Can KIRO Fill work outside the Cleanroom?

It is recommended that KIRO Fill be placed in an ISO Class 7 buffer room, adjacent to an ISO class 8 ante area, to obtain full beyond-use-dating of end products per USP Chapter 797 or comply with cGMP requirements. KIRO Fill may also be placed in a Segregated Compounding Area (SCA) that meets the requirements of USP Chapter 797.

Contact our experts to discuss your sterile compounding needs and plans for the future.