Secondary Engineering Controls E. Clyde Buchanan

Transcription

1 21 Secondary Engineering Contros E. Cyde Buchanan Introduction Functiona Requirements Air Ceaniness CSP Microbia Contamination Risk Leves Hazardous Drugs Radiopharmaceuticas Aergen Extracts Immediate-use Provision Proprietary Bag and Via Systems Other Reguatory Requirements for Faciities Buffer Area and Ante-area Heating, Ventiation, and Air Conditioning (HVAC) Surface Characteristics Pacement of Equipment and Suppies Environmenta Samping and Testing Ceaning and Disinfecting Panning the Sterie Preparation Faciity Strategic Master Faciities Pan Existing Faciity Functiona Program Architectura Schematic Pan Construction Contract Construction Commissioning for Occupancy Faciity Maintenance Ceaning and Disinfecting Re-Certification Environmenta Samping and Testing Corrective Actions Summary References

2 Compounding Sterie Preparations Introduction Reguatory standards and professiona guideines (see Chapter 1 and Appendixes) require that pharmacists evauate their sterie compounding faciities. Standards and guideines specify that sterie preparations be compounded in an area separate from other pharmacy activities. The most prominent standard, USP Chapter <797>, Pharmaceutica Compounding Sterie Preparations, requires that most sterie compounding be done within an ISO Cass 5 primary engineering contro that is propery paced in a buffer area supported by an ante-area 1 Chapter <797> stresses that empoyee training and evauation on garbing, hand ceansing, maintaining aseptic technique in an ISO Cass 5 environment and disinfecting goves are the most important determinants eading to compounded preparations that are free from viabe microorganisms and pyrogens. However, for primary engineering contros to work propery (see Chapter 4) and for personne to maintain aseptic technique, a cean compounding area is mandatory. Further, Chapter <797> sets forth standards for handing hazardous drugs to protect the compounder and the environment from contamination with toxic substances. This chapter expains the functiona requirements of a sterie compounding area, how to pan new sterie compounding areas or to ater existing ones, and how to purchase, vaidate and certify sterie compounding areas. Functiona Requirements Functiona requirements foow USP Chapter <797> because this is the enforceabe standard toward which most pharmacists strive. Anti-areas and buffer areas or ceanrooms are known coectivey as secondary engineering contros because they provide the controed environments in which primary engineering contros (aminar air fow workbenches, bioogica safety cabinets and compounding isoators) are paced. Air Ceaniness To foow USP Chapter <797>, pharmacists must understand controed environment cassifications. For neary 40 years, U.S. Federa Standard 209 (FS 209) defined air ceaniness in contamination contro, 2 but FS 209 has been retired by the U.S. Genera Services Administration 3 in favor of the internationay-accepted definitions for ceanrooms and cean zones promugated by the Internationa Organization of Standardization (ISO). 4 See Tabe CSP Microbia Contamination Risk Leves For the most part, USP Chapter <797> sets standards according to microbia contamination risk eves. The appropriate risk eve Tabe Internationa Organization of Standardization (ISO) Cassification of Particuate Matter in Room Air as Limits in Partices 0.5 Microns and Larger per Cubic Meter (Current ISO) and Cubic Feet (Former FS 209E) 2 Cass Name Partice Counts Per ISO Cass U.S. FS209E ISO, m 3 FS209E, ft 3 3 Cass Cass Cass Cass , Cass 10, ,000 10,000 8 Cass 100,000 3,520, ,000 Source: Adapted by USP from the Federa Standard 209e, Genera Services Administration, Washington, DC (September 11, 1992) and ISO :1999 Ceanrooms and associated controed environments part 1: Cassification of air ceaniness. 260

3 Chapter 21 Secondary Engineering Contros ow, medium, or high is assigned according to the corresponding probabiity of contaminating a CSP with (1) microbia contamination (e.g., microbia organisms, spores, endotoxins) and (2) chemica and physica contamination (e.g., foreign chemicas, physica matter). 1 Chapter <797> appies more stringent faciity requirements to high risk eve compounding as compared to ow- and medium-risk compounding (see Tabe 21-2). Low-Risk Leve CSPs with 12-Hour or Less Beyond-use Date If the primary engineering contro (PEC) is a compounding aseptic isoator (CAI) or a compounding aseptic containment isoator (CACI) that does not meet the requirements described in USP Chapter <797> or is a aminar airfow workbench (LAFW) or a bioogica safety cabinet (BSC) that cannot be ocated within an ISO Cass 7 buffer area, then ony ow-risk eve nonhazardous and radiopharmaceutica CSPs pursuant to a physician s order for a specific patient may be prepared, and administration of such CSPs must commence within 12 hours of preparation or as recommended in the manufacturers package insert, whichever is ess. Low-risk eve CSPs with a 12-hour or ess beyond-use date (BUD) must meet a four of the foowing criteria 1 : PECs (LAFWs, BSCs, CAIs, and CACIs), must be certified and maintain ISO Cass 5 as described in USP Chapter <797> for exposure of critica sites and must be in Tabe Secondary Engineering Contro Requirements by USP Chapter <797> Risk Leve* Low Risk Ante-area An ISO Cass 8 (see Tabe 21-1) or ceaner area where personne hand hygiene and garbing procedures, staging of components, order entry, CSP abeing, and other high-particuate-generating activities are performed. Buffer area An ISO Cass 7 (see Tabe 21-1) or ceaner area where the primary engineering contro is physicay ocated. Activities that occur in this area incude the preparation and staging of components and suppies used when compounding CSPs. Ante-area and buffer area may be separated by a ine of demarcation or by a physica barrier ike a wa, door, and pass-through. Buffer area must have at east 30 air changes per hour (ACPH), or as itte as 15 ACHP if a aminar air-fow workbench provides as much as 15 ACHP. HEPA-fitered air must be introduced at the ceiing and air return vents shoud be mounted ow on the was. A temperature of 20 degrees Cesius (68 degrees Fahrenheit) or cooer shoud be maintained by the heating, ventiation, and air conditioning system. Surfaces of ceiings, was, foors, fixtures, counters, and cabinets in the buffer area must be smooth, impervious, free from cracks and crevices, nonshedding, and resistant to damage by disinfectants. Medium Risk Same as ow-risk eve. High Risk Same as ow-risk eve except that: ante-area must be physicay separated from the buffer area by a wa, door, and pass-through. *Source: U.S. Pharmacopeia Convention. Chapter <797> Pharmaceutica Compounding: Sterie preparations. Chapter797.htm. Accessed on March 3,

4 Compounding Sterie Preparations a segregated compounding area restricted to sterie compounding activities. The segregated compounding area cannot be in a ocation that has unseaed windows or doors that connect to the outdoors or high traffic fow, or that is adjacent to construction sites, warehouses, or food preparation, etc. Personne must foow ceansing, garbing and other personne procedures described in USP Chapter <797> prior to compounding. Sinks shoud not be ocated adjacent to an ISO Cass 5 PEC. The USP Chapter <797> specifications in ceaning and disinfecting the sterie compounding areas, personne training and competency evauation of garbing, aseptic work practices and ceaning/disinfection procedures, and viabe and nonviabe environmenta air samping must be foowed as described in Chapter <797>. See Tabe 21-3 for a summary of secondary engineering contros required for each cassification of compounded sterie preparation (CSP). CAIs and CACIs must be paced in an ISO Cass 7 buffer area uness they meet a of the foowing conditions 1 : The isoator must provide isoation from the room and maintain ISO Cass 5 during dynamic operating conditions, incuding transferring ingredients, components, and devices into and out of the isoator and during preparation of CSPs. Partice counts samped approximatey 6 to 12 inches upstream from the critica exposure site must maintain ISO Cass 5 eves during compounding operations. Not more than 3520 partices (0.5 microns and arger) per cubic meter can be counted during materia transfer, with the partice counter probe ocated as near to the transfer door as possibe without obstructing the transfer. Compounding personne must obtain documentation from the manufacturer that the CAI or CACI wi meet the conditions above when ocated in environments where the background partice counts exceed ISO Cass 8. 1 Hazardous Drugs USP Chapter <797> states that hazardous drugs must be prepared ony under conditions that protect heathcare workers and other personne in the preparation and storage areas. 1 This means not just the sterie compounding areas but where ever hazardous drugs are received, stored, handed, compounded or transported. Hazardous drugs must be stored separatey from other inventory so as to prevent contamination and personne exposure. Many hazardous drugs have sufficient vapor pressures to aow voatiization at room temperature; thus storage shoud be within a containment area such as a negative pressure room. The storage area shoud have sufficient genera exhaust ventiation, at east 12 air changes per hour (ACPH), to diute and remove any airborne contaminants. 1 The USP s expert Sterie Compounding Committee (SCC) 5 states that the negative pressure storage conditions protect personne outside the compounding area from hazardous drug exposure at a minima risk of ingress of airborne contamination. Further, there may be no need for an additiona negative pressure room for hazardous drug storage. That is, smaer voume hazardous compounding faciities can simpy store the hazardous drugs in the chemotherapy compounding buffer room, which shoud aready meet the minimum criteria for hazardous drug storage. 5 A hazardous drugs must be prepared in a bioogica safety cabinet (BSC) or a compounding aseptic containment isoator (CACI). The ISO Cass 5 BSC or CACI must be paced in an ISO Cass 7 buffer area that is physicay separated (i.e., a different room from other preparation buffer areas) and optimay has not ess than 0.01-inch water coumn negative pressure to adjacent positive pressure ISO Cass 7 or better ante-area, thus providing inward airfow to contain any airborne drug. A pressure indicator must be instaed that can be readiy monitored for correct room pressurization. The BSC and CACI shoud be 100% vented to the outside air through HEPA fitration. 1 There is no requirement for a separate anteroom for the negative pressure ISO Cass 7 buffer room. The same ante-room can be used for both non hazardous and hazardous buffer rooms. The difference in cost of making the ante-room ISO cass 7 instead of ISO cass 8 is minima. For exampe, using a reativey arge ante-room size of 10 foot x 10 foot with an 8-foot ceiing (tota voume of 800 cubic feet) the difference to go from 20 ACPH (266 cubic feet per minute [CFM]) as appropriate for an ISO cass 8 room to a minimum of

5 Chapter 21 Secondary Engineering Contros Tabe Summary of Secondary Engineering Contros Required for Each Cassification of Compounded Sterie Preparation (CSP) Type of CSP per USP Chapter <797> Low risk Medium risk High risk Low risk with ess than 12-hour BUD* Ante-Area ISO Cass Requirement Buffer Area Cass 8 positive pressure to main pharmacy and either physicay separated from buffer area by a wa or by dispacement air fow Cass 8 positive pressure to main pharmacy and either physicay separated from buffer area by a wa or by dispacement air fow Cass 8 positive pressure to main pharmacy and physicay separated from buffer area by a wa Cass 7 positive pressure to ante-area Cass 7 positive pressure to ante-area Cass 7 positive pressure to ante-area Segregated Compounding Area Not required Not required Demarked area or room restricted to preparing ow-risk CSPs with 12-hour or ess BUD Immediate use with one hour or ess BUD Not required Not required Not required Hazardous drug Radiopharmaceutica Aergen extract appropriatey preserved for intraderma or subcutaneous injection Proprietary bag and via system Separate Cass 7 positive pressure to buffer room Separate Cass 7 negative pressure buffer room Cass 8 or better for Tc99m or Mo99 Low-risk with 12-hour or ess BUD radiopharmaceutica with ine of demarcation Not required Not required Not required Not required Not required Not required *BUD, beyond-use date. ACPH (399 CFM) for an ISO cass 7 space ony requires 133CFM. In either case, a of the suppy air can be deivered through one HEPA fiter. 5 If a CACI that meets the USP Chapter <797> requirements above, is used outside of an ISO Cass 7 buffer area, the separate compounding area must maintain a minimum negative pressure of 0.01-inch water coumn and have a minimum of 12 ACPHs. 1 In a heath care institution that prepares a ow voume of hazardous drugs, the use of two tiers of containment (i.e., a cosed-system transfer device [e.g., PhaSea ] with a BSC or a CACI that is ocated in a non-negative pressure 263

6 Compounding Sterie Preparations room) is acceptabe. 1 The decision as to what is ow voume is eft to the sterie compounding institution. Radiopharmaceuticas USP Chapter <797> specifies that radiopharmaceuticas must be compounded using appropriatey shieded vias and syringes in a propery functioning and certified ISO Cass 5 PEC ocated in an ISO Cass 8 or ceaner air environment to permit compiance with specia handing, shieding, and negative air fow requirements. Storage and transport of propery shieded vias of radiopharmaceutica CSPs may occur in a imited access ambient environment without a specific ISO cass designation. 1 Technetium-99m/moybdenum-99 generator systems must be stored and euted under conditions recommended by manufacturers and appicabe state and federa reguations. Such generator systems must be euted in an ISO Cass 8 or ceaner air environment to permit specia handing, shieding, and air fow requirements. Radiopharmaceuticas prepared as Low-Risk Leve CSPs with 12-hour or ess beyond-use dating must be prepared in a segregated compounding area. A ine of demarcation defining the segregated compounding area must be estabished. Materias and garb exposed in a patient care and treatment area must not cross a ine of demarcation into the segregated compounding area. 1 See Chapter 8 on Radiopharmaceuticas as CSPs. Aergen Extracts The USP s expert Sterie Compounding Committee (SCC) added the new section tited Aergenic Extracts as CSPs based on evidence that 27,000 immunotherapy injections, which were not prepared in ISO cassified controed environments by personne goved and garbed according to standards specified in the chapter for ow- and medium-risk eve CSPs, were not associated with any infections. 6 USP Chapter <797> specifies suitaby-preserved aergen extracts as CSPs are not subject to the environmenta, and beyond-use date storage requirements for a CSP microbia contamination risk eves but ony when a of eeven criteria isted in Chapter <797> are met. Non-preserved aergen extract CSPs must compy with the appropriate Chapter <797> CSP risk eve requirements, regardess of whether compounded by pharmacist, physician or other trained personne. Aergen extract compounders must foow specified hand ceansing, garbing and aseptic techniques and abeing standards. 1 Therefore, suitabe space is required for compounding and storage of equipment, suppies and finished preparations. Chapter <797> mandates no standards for aergen extract compounding faciities. However, the Joint Commission does have faciity standards for medication preparation (see other reguatory requirements beow). See aso Chapter 9 on Aergen Extracts as CSPs. Immediate-use Provision USP Chapter <797> restricts the immediateuse provision to those situations where there is a need for emergency or immediate patient administration of a CSP, e.g., cardiopumonary resuscitation, emergency room treatment, preparation of diagnostic agents, or critica therapy where the imposition of ow-risk operating conditions subjects the patient to additiona risk due to deays in therapy. When CSPs meet a six immediate use conditions, Chapter <797> mandates no standards for compounding faciities. However, the Joint Commission does have faciity standards for medication preparation (see other reguatory requirements beow). Proprietary Bag and Via Systems USP Chapter <797> aows an exemption to risk eve faciity standards for proprietary bag and via systems. The steriity storage and stabiity beyond-use times for attached and activated (where activated is defined as aowing contact of the previousy separate diuent and drug contents) container pairs of drug products for intravascuar administration (e.g., ADD- Vantage, Mini Bag Pus, AddAVia, Add- Ease, Dupex ) is to be appied as indicated by the manufacturer. 1 However, the Joint Commission does have faciity standards for medication preparation (see other reguatory requirements beow). Other Reguatory Requirements for Faciities In addition to USP Chapter <797> standards for air ceaniness, two reguatory organizations have requirements for sterie preparation 264

7 Chapter 21 Secondary Engineering Contros faciities. The Food and Drug Administration (FDA) requires pharmacists to use good manufacturing practices, 7 incuding a faciity of suitabe size, construction, and ocation to faciitate ceaning, maintenance, and proper operations. Second, the Joint Commission on Accreditation of Heathcare Organizations (Joint Commission ) standards for hospitas simpy state 8 : Whenever medications are prepared, staff uses appropriate techniques to avoid contamination during medication preparation, which incude but are not imited to: Using cean or sterie techniques Maintaining cean, uncuttered, and functionay separate areas for product preparation to minimize the possibiity of contamination Using a aminar-airfow hood or other Cass 100 environment whie preparing any intravenous (IV) admixture in the pharmacy, any sterie product made from non-sterie ingredients, or any sterie product that wi not be used within 24 hours Visuay inspecting the integrity of the medications Dispensing adheres to aw, reguation, icensure, and practice standards, incuding record keeping. 9 In preventing pediatric medication errors, the Joint Commission sets forth risk reduction strategies, incuding, at a minimum, pediatric medications shoud be stored and prepared in areas separate from those where adut medications are stored and prepared. 10 Buffer Area and Ante-area Heating, Ventiation, and Air Conditioning (HVAC) Under USP Chapter <797>, sterie compounding areas must provide a comfortabe and we-ighted working environment, which typicay incudes a temperature of 20 C. or cooer, to maintain comfortabe conditions for compounding personne to perform fawessy when attired in the required aseptic compounding garb. Buffer areas are designed to maintain at east ISO Cass 7 conditions for 0.5-micron partices under dynamic conditions and ISO Cass 8 conditions for 0.5-micron and arger partices under dynamic conditions for the ante-areas. The buffer area must be segregated from surrounding, uncassified spaces to reduce the risk of contaminants being bown, dragged, or otherwise introduced into the fitered unidirectiona airfow environment, and this segregation must be continuousy monitored with a pressure gauge. For sterie compounding areas providing a physica separation between buffer and ante areas through the use of was, doors, and pass-throughs, a minimum differentia positive pressure of to 0.05-inch water coumn is required. For buffer areas not physicay separated from the ante-areas, the principe of dispacement airfow must be empoyed. This concept utiizes a ow pressure differentia, high airfow principe. Using dispacement airfow typicay requires an air veocity of 40 feet per minute or more from the buffer area across the ine of demarcation into the ante-area. 1 The dispacement concept must not be used for high-risk compounding. PECs must be paced within a buffer area in such a manner as to avoid conditions that coud adversey affect their operation. For exampe, strong air currents from opened doors, personne traffic, or air streams from the HVAC systems can disrupt the unidirectiona airfow in open-faced LAFWs. 1 HEPA fiters shoud be ocated above the ceiing the air fowing in a unidirectiona manner into the buffer area and ante-area. The HEPA fiter in the ceiing air suppy shoud be paced to avoid creating air currents inside the aminar-airfow workbench. Pre-fiters on the heating, ventiation, and air conditioning (HVAC) air bower shoud be changeabe from outside the ante-area/buffer area. 11 Air return gris shoud be ocated ow on the was. Low wa mounted air returns are somewhat more difficut to insta but are much more efficient in remova of airborne particuate contamination. Low wa returns shoud be we distributed throughout the room and ideay have adjustabe ouvers or dampers. 12 Surface Characteristics USP Chapter <797> stipuates that the surfaces of ceiings, was, foors, fixtures, sheving, counters, and cabinets in the buffer area must be smooth, impervious, free from cracks and 265

8 Compounding Sterie Preparations crevices, and nonshedding, thereby promoting ceanabiity and minimizing spaces in which microorganisms and other contaminants may accumuate. The surfaces must be resistant to damage by disinfectant agents. Junctures of ceiings to was must be coved or cauked to avoid cracks and crevices where dirt can accumuate. 1 If ceiings consist of inaid panes, the panes must be impregnated with a poymer to render them impervious and hydrophobic, and they must be cauked around each perimeter to sea them to the support frame. Was may be constructed of fexibe materia (e.g., heavy gauge poymer) panes ocked together and seaed, or of epoxy-coated gypsum board. Preferaby, foors are overaid with wide sheet viny fooring with heat-weded seams and coving to the side-wa. Dust-coecting overhangs, such as ceiing utiity pipes, and edges, such as windowsis, shoud be avoided. The exterior ens surface of ceiing ighting fixtures shoud be smooth, mounted fush, and seaed. Any other penetrations through the ceiing or was must be seaed. 1 The buffer area must not contain sources of water (e.g. sinks, eye washes) or foor drains. Work surfaces must be constructed of smooth, impervious materias, such as stainess stee or moded pastic, so that they are easiy ceaned and disinfected. Storage sheving, counters, and cabinets must be smooth, impervious, free from cracks and crevices, nonshedding, ceanabe, and disinfectabe. Their number, design, and manner of instaation must promote effective ceaning and disinfection. 1 Pacement of Equipment and Suppies USP Chapter <797> expains that the quaity of the environmenta air improves with movement from the outer boundary of the ante-area to the direct compounding area (DCA) within PECs. Pacement of devices in ante-areas and buffer areas is dictated by their effect on the designated environmenta quaity of atmospheres and surfaces, which must be verified by viabe (microbia) and non-viabe (particuate) air samping. 1 See Chapter 24. It is the responsibiity of every sterie compounding supervisor to ensure that each PEC environment for exposure of critica sites and steriization by fitration is propery ocated, operated, maintained, monitored, and verified (see Chapter 4). Pacement of devices (e.g., computers, printers) and objects (e.g., carts, cabinets) that are not essentia to compounding in buffer areas is dictated by their effect on the required environmenta quaity of air and surfaces, which must be verified by viabe and nonviabe air samping. 1 Space must be provided in or convenient to the ante-area for storage of sterie garb (gowns, goves, hair and shoe covers, face masks and gogges) and for suppies that are needed for equipment (e.g., pre-fiters for PECs, automatic compounder sets, abes, etc.). With regard to non-sterie chemicas used in high-risk compounding, USP Chapter <1075>: Good compounding practices says that buk drugs and other chemicas or materias used in the compounding of drugs must be stored as directed by the manufacturer, or according to USP monograph requirements, in a cean, dry area, under appropriate temperature conditions (controed room temperature, refrigerator or freezer). 13 Presteriization procedures for high risk eve CSPs, such as weighing and mixing, must be competed in no worse than an ISO Cass 8 environment (e.g. in a separate room with a controed air environment). A high risk eve CSP soutions subjected to termina steriization are pre-fitered by passing through a fiter with a nomina pore size not arger than 1.2 microns preceding or during fiing into their fina containers to remove particuate matter. A nonsterie measuring, mixing, and purifying devices are rinsed thoroughy with sterie, pyrogen-free water, and then thoroughy drained or dried immediatey before use for high-risk compounding. 1 Environmenta Samping and Testing USP Chapter <797> specifies that the environmenta samping and testing program must demonstrate that PECs (LAFWs, BSCs, CAIs, and CACIs) are maintaining an environment in the compounding area that consistenty ensures acceptaby ow viabe and nonviabe partice eves. The compounding area incudes the ISO Cass 5 PEC, the buffer areas, and/ or segregated compounding areas and the ante-areas. 1 Environmenta samping must occur as part a comprehensive quaity management program and must occur minimay under any of the foowing conditions: 1) as part of the commissioning and certification of new facii- 266

9 Chapter 21 Secondary Engineering Contros ties and equipment; 2) foowing any servicing of faciities and equipment; 3) as part of the re-certification of faciities and equipment (i.e., every six months); 4) in response to identified probems with end products or staff technique; or 5) in response to issues with CSPs, observed compounding personne work practices, or patient-reated infections (where the CSP is being considered as a potentia source of the infection). 1 Therefore, suitabe space must be provided for samping swabs, agar pates, incubator, etc. See Chapter 24 on environmenta quaity and contro. Ceaning and Disinfecting USP Chapter <797> states, Environmenta contact is a major source of microbia contamination of CSPs. Consequenty, scrupuous attention to ceaning and disinfecting the sterie compounding areas is required to minimize this as a source of CSP contamination. 1 Therefore, appropriate space must be provided for ceaning suppies, sterie 70% isopropy acoho and other disinfectants, trash containers for a waste streams invoved, etc. See Chapters 15 and 23. Panning the Sterie Preparation Faciity Aen et a. presented a detaied panning process for designing and evauating a sterie compounding faciity. 14 The authors used a strategic functiona panning approach. This aowed them to meet hospita goas for efficiency, functionaity and a panned future reocation of the sterie compounding center. The functiona program deveopment took them through: work fow, work oad, equipment, storage, arrangement of work areas, space requirements, foor pan and evauation of the faciity. They were abe to improve pharmacist efficiency by 42% and technician efficiency by 29% within a modest-sized faciity that met ASHP sterie compounding faciity standards extant in The cost of the equipment and fixtures was $70,000 $75, The functiona panning approach incudes eight key steps that can be used for arge or sma construction projects 16 : 1. Strategic master faciities pan sets forth the impications of the hospita strategic pan in terms of the faciities needed to accommodate panned activities, aong with a timeine to show when faciity needs wi occur. The pharmacy department shoud have its own master faciities pan, keyed to its strategic pan, and congruent with the hospita s strategic pan. 2. Anaysis of existing faciity incudes asbuit pans, space inventory room by room, equipment ist showing age and repacement vaue, site surveys, assessment of structura, mechanica, and eectrica systems, code conformity, and traffic patterns. 3. Functiona program incudes bock diagrams that show department components, fow and traffic reationships, phases in deveopment, new versus renovated space, gross cost estimate, and a statement of assumptions and priorities. 4. Architectura schematic pans incude aternatives, showing ayout and design of departments and reationships pus workfow of staff, materias, and patients (incudes a brief description of fixtures, mechanica and eectrica systems, and a cost estimate). 5. Architectura design adds a other architectura detais, incuding the ast review by the users. 6. Construction contract incudes fina drawings for reguatory approva and bidding pus the fina cost estimate. 7. Construction incudes demoition, construction, equipment ordering, and inspection. 8. Commissioning for occupancy incudes instaation of equipment, orientation of staff, moving, post-occupancy evauation (i.e., vaidation, certifications), and foowup. Strategic Master Faciities Pan The first step, deveoping a master faciities pan, invoves identifying and justifying the need for a new faciity. Identifying Need Before updated faciities can be justified, the pharmacy department must determine its specific need based on its patient popuation. Three questions can be asked to determine this need. What guideines appy to the patient popua- 267

10 Compounding Sterie Preparations tion? Some state pharmacy aws or reguations require that USP Chapter <797> standards be foowed. See Chapter 1. What are the highest eve sterie preparations that wi be compounded? Uness there is no chance that high-risk preparations wi ever be compounded, foowing the USP Chapter <797> standards for high-risk compounding is the most conservative approach. Wi hazardous drugs be compounded? Compounding hazardous drugs wi require additiona primary (i.e., BSC or CACI) and secondary engineering (i.e., segregated negative pressure buffer room) contros. Justifying Need Pharmacy directors frequenty face resistance (both from administrators and pharmacy personne) when justifying the need to improve their faciities. Some commony asked questions and their corresponding answers foow. Q. If admixtures are made within a aminarairfow workbench, why does its ocation matter? A. Laminar-airfow workbenches do not eiminate 100% of airborne partices. These workbenches have high-efficiency particuate air (HEPA) fiters that remove 99.97% of partices over 0.3 microns when operating propery. 17 A significant increase in airborne contamination outside the workbench significanty increases contamination within the workbench. Workbenches cannot prevent microbia contamination introduced by poor aseptic technique downstream from the HEPA fiter (e.g., from air currents pushing room air into the workbench). Q. If the workbench is aready in a separate room, do you reay need a buffer area and ante-area? A. A separate room minimizes unnecessary traffic near the workbench but not the contamination aready in a room. For exampe 17 : A person sitting motioness generates about 100,000 partices/cu ft/min. A person sitting down or standing up generates about 2,500,000 partices/cu ft/min. A person waking generates about 10,000,000 partices/cu ft/min. An open, non-airocked door can add biions of partices/cu ft/min. The primary functions of a we-designed buffer area are to remove internay generated contamination and to prevent it from adversey affecting the direct compounding area (i.e., inside workbench environment). 17 Q. If pharmacy-prepared admixtures at this hospita have never been impicated in nosocomia infections, why shoud these faciities be upgraded? A. Pharmacy-prepared sterie preparations are not commony impicated because few institutions thoroughy investigate the causes of nosocomia infections. In fact, pharmacy-compounded sterie preparations have often been traced back to poor pharmacy aseptic compounding technique (see Chapter 1). Q. Isn t good aseptic technique more important than a buffer area in preventing microbia contamination? A. One study showed that when sterie preparations are contaminated, touch contamination (as evidenced by skin bacteria) is much more common that contamination from the environment. 18 However, we-maintained buffer areas provide a cean, comfortabe, correcty-arranged environment for primary engineering contros optimay to create an aseptic direct compounding area where critica sites can be exposed. Requiring proper personne garbing and hand ceansing prior to entering a buffer area aso minimizes unnecessary traffic in the area of compounding. Q. Since buiding an ante-area and buffer area wi be expensive, why not return the responsibiity for admixture preparation to nurses? A. True, in admixtures prepared just prior to administration, accidentay introduced microbes have ess time to grow to pathoogica eves. But one study showed that 21% of the admixtures were made incorrecty (as to ingredients, dosage, unordered admixture, or incompatibiity) on nursing units. 19 Moreover, nurses are ess we trained to make admixtures today than when this study was pubished. Furthermore, since many sterie preparations are used for 24 hours or more (e.g., TPNs and patient-controed anagesia syringes), microbes can easiy grow to pathoogic eves at room or body temperatures. USP Chapter <797> does exempt manufacturer s bag and via systems from a chapter standards and this exemption is used in many hospitas for critica patient needs. 20 Q. Finay, what agency is going to force our institution to adopt USP Chapter <797> 268

11 Chapter 21 Secondary Engineering Contros sterie compounding faciity standards? A. The state board of pharmacy is the most powerfu agency inspecting pharmacies. At east nine states require partia or fu compiance with USP Chapter <797> and most state boards of pharmacy are reviewing the new Chapter <797> to decide whether or how to enforce this chapter. The Joint Commission requires accredited heath care institutions to review and decide how to use Chapter <797>. Courts of aw wi use Chapter <797> as the community standard for sterie compounding. See Chapter 1. Dougas recommends that pharmacy directors write a 5 to 10 page white paper to justify physica pant changes to bring pharmacy into conformance with USP Chapter <797>. 21 To be effective, the white paper shoud address: reguatory standards, patient safety improvement and reduced potentia for itigation, fisca impact as to personne efficiency, capita expenditures and return on investment, competitive advantage in the heath care market, aternative soutions and why they were rued out. 22 Determine the stakehoders who wi read the white paper. Use anguage that is famiiar to the stakehoders, e.g., patient and empoyee safety, finances, reguations. Use tabes to present more detaied information, ike aternatives considered pros and cons, effects on staff efficiency, buiding, equipment and suppy costs. Aen et a. found that their open sterie compounding center required 727 square feet in foor space incuding a separate hazardous drug compounding area for a teaching hospita with an average of 441 occupied beds and 800 IV admixtures per day. 14 For hand washing, a sink with hot and cod running water shoud be in the antearea but not the buffer area. Ventiation and room temperature contro shoud be in accordance with USP Chapter <797> standards (See above discussion). In any encosed space with heat-producing equipment, the air conditioning must keep personne comfortabe in ceanroom garb. Lighting shoud ensure that personne can read packages easiy (e.g., syringe gauges and drug abes) and visuaize contaminants (e.g., gass fragments in ampus and rubber cores in vias). 24 Room Separation An ISO Cass 7 buffer area and ISO Cass 8 ante-area are mandatory. Seventeen percent of hospita pharmacies compound high-risk preparations. 25 Any hospita that compounds, or has the potentia to compound, high-risk preparations must have the ante-area separated from the buffer area by a soid wa with a door that coses. 1 See section on open and cosed sterie compounding faciities beow. Existing Faciity Once the need has been justified, the next step is to determine whether a current sterie compounding area can be updated, whether a new compounding area is needed, or whether a new type of environmenta contro (e.g., compounding isoator) shoud be empoyed. Room size and environment (e.g., temperature, humidity and ighting) as we as ceaniness eves are important considerations. Size and Environment A survey conducted in 2006 of 341 U.S. hospitas showed an average of 310 square feet of foor space aocated for compounding sterie preparations (see Tabe 21-4). Considering that a minority of hospitas had upgraded their sterie compounding faciities in ine with USP Chapter <797>, 81.3% of respondents to this survey indicated that their space aocations were not adequate for sterie compounding. 23 Tabe Space Aocation for Sterie Compounding Areas* Number of Staffed Beds Square Footage (mean ± S.E.) < 50 (n = 40) (n = 65) (n = 57) (n = 52) (n = 61) > 400 (n = 66) A hospitas (n = 341) *Source: Pederson CA, Schneider PJ, Scheckehoff DJ. ASHP nationa survey of pharmacy practice settings: Monitoring and patient education Am J Heath-Syst Pharm. 2007;64:

12 Compounding Sterie Preparations Functiona Program The functiona program is a arge voume of detaied performance specifications to provide the designer or architect with detais for a sterie compounding and reated activities, work fows, work oads, numbers of personne to be accommodated, fixtures and equipment, storage needs, transportation and communications, services, utiities environmenta contros, security considerations, etc. 16 The key point in functiona programming is to identify every specific function aong with the required methods and systems to be performed in the faciity. After existing faciities have been anayzed, one primary decision has to be made: Shoud a custom-buit ante-area/ buffer area be panned or shoud a moduar ante-area/buffer area be purchased? Or can an existing room be remodeed or procedures be impemented to create a faciity that meets ante-area/buffer area air quaity standards? Ante-Areas and Buffer Areas A high-ceaniness ante-area reduces the number of partices in the buffer area. Appropriate activities for the anteroom incude but are not imited to hand washing, gowning and goving, remova of packaging, and ceaning and disinfecting of hard-surface containers and suppies before they are paced in the buffer area. 1 See Chapter 15. Figure 21-1, from proposed USP Chapter <797>, shows the important parts and spatia reationship of a buffer area to an ante area suitabe for ow and medium risk sterie compounding. 26 This configuration is sometimes referred to as an open ceanroom. Figure 21-2 represents USP s schematic foor pan for a high-risk sterie compounding faciity. 26 This configuration is sometimes referred to as a cosed ceanroom. Access to the buffer room shoud be via the anteroom door for personne and via an airock pass through Figure Schematic drawing of an open ante-area and buffer-area (not to scae). 270

13 Chapter 21 Secondary Engineering Contros for most suppies. As suppies are moved from the anteroom into the buffer room and then into the PEC, a series of ceaning steps shoud be foowed (see Chapter 15). Moduar Ante-Area/Buffer Areas Moduar ante-area/buffer areas (as opposed to custom buit) have severa advantages: 1. Moduar ante-area/buffer areas can be customized to specific needs of the institution. 2. No sanding, spacking, or painting of was are necessary, eaving a ceaner environment. 3. Moduarity aows future change if changes are anticipated in aseptic processes or voume, or reocation to another site. 4. Moduar ante-area/buffer areas cost ess and are more rapidy instaed, reducing construction time by 20% to 40% Moduar systems use standard components that are often avaiabe from different suppiers. 6. Shipping costs for auminum and viny components are ess costy than stee and unassembed components. 7. Instaation costs are ess because the vendor wi do most of the instaation, with the exception of eectrica, water and HVAC hook-ups. For ow-voume operations, soft-wa antearea/buffer areas are avaiabe at a ower cost than moduar hard-wa instaations. The pharmacy at Memoria Hospita in Carthage, IL, had a soft-wa ante-area/buffer area (Figure 21-3) instaed for under $20,000 (in 1995 doars) that satisfied a JCAHO home care survey. Some facts about this ante-area/ buffer area incude 28 : Setup of tubuar frame and viny pastic panes took hours for two company personne. Dimensions are 8 feet by 16 feet, with an 8-feet ceiing height. Three movabe was are connected to one rigid wa. The rigid wa contains eec- Figure Schematic drawing of a cosed anteroom and buffer room (not to scae). 271

14 Compounding Sterie Preparations 272 trica and pumbing fixtures. It is made of auminum stud supporting fire-rated dry wa and is painted with epoxy paint to provide durabiity and prevent partice shedding. Soft was are made of 16-mi, repaceabe, cear viny panes attached to a strong tubuar frame. The ante-area/buffer area door is the same viny-on-tubuar frame construction. The pass-through chamber is 16 inches by 16 inches. Two 2-feet by 4-feet HEPA fiters are suspended in the ante-area/buffer area ceiing. Air from the pharmacy proper is bown through two standard fibergass fiters before passing through the HEPA fiters into the ante-area/buffer area. Louvered dampers in the door and beow the pass-through chamber permit airfow out of the positive-pressure room. They can be cosed if power is ost to the bower. Ceiing ties are viny-coated gypsum panes. Viny panes are easy to cean with detergent and water and can be repaced inexpensivey if torn. A hands free faucet and hand dryer are just outside the ante-area/buffer area. The airborne partice count in the ceanroom is about 65 of 0.5 microns or arger per cubic foot, easiy quaifying the environment as ISO Cass 7 or even ISO Cass 5. Partice counts inside the aminarairfow workbench average 5 10 of 0.5 microns or arger. Compared to soft-wa ante-area/buffer areas, hard-wa moduar ante-area/buffer areas with rigid panes attached to a frame offer more stabiity and better seas to maintain ante-area/buffer area integrity. 29 Hard-wa ante-area/buffer areas are aso easier to keep cean and are more durabe. Remodeing Existing Space Kuster and Snyder gave reasons for renovating their pharmacy to create an ISO Cass 7 ante-area/buffer area. 30 They prepared various sterie preparations, incuding high-risk preparations such as gycerin and pheno injection and sterie tac injection. To essen Figure Pharmacist in a soft-wa ceanroom at Memoria Hospita, a 67-bed hospita in Carthage, IL. the chance of error due to interruptions, they paced no phone in their ante-area/buffer area and incuded ony a foot-activated intercom for outside communications. Samueson and Cark described the panning for an ISO Cass 7 buffer area with an ISO Cass 8 anteroom at the University of Iinois Hospita. 31 They decided to convert an existing 32-feet by 22-feet sterie preparations room 40% into a buffer area and 60% into an ante-area by constructing a wa across it. The arge anteroom was needed for stock storage and reference materias. A arger passthrough window was used for suppies going into the buffer area, and the smaer window, for competed preparations going back to the ante-area where a pharmacist checks them. The gass pane around the windows preserved a sense of openness and aows the pharmacist to monitor activities in the ante-area/buffer area. Since the existing was and foor were seamess, they coud be seaed with a poymer coating. However, ventiation had to be changed to incorporate HEPA fitration of the air suppy in conjunction with a new two-inch ceiing grid system. In a 321-bed community hospita, Schumock et a. described their remodeing project to create an ISO Cass 7 buffer room. 32 The authors panned and impemented a 361 square foot faciity that paid for itsef ($39,486 in 1996 doars) in ess than two years via the batch production of seected unit-of-use

15 Chapter 21 Secondary Engineering Contros syringes not avaiabe commerciay, i.e., savings were from reduced waste and extended expiration dating. Minima Faciity Change Pharmacy managers find it tempting to convert a traditiona sterie compounding space to an ante-area, buffer area space. This is difficut for severa reasons. Adding enough ante-area usuay takes more space; there may not be enough overhead space for adding HEPA fiters and their air gris; ow wa air returns can be a probem; adding pumbing for a sink in the ante-area is tough if the pharmacy is on the bottom foor; exhausting a BSC or CACI to the outside for compounding hazardous drugs may be difficut and so on. Remodeing existing space aso poses the difficuty of finding swing space for sterie compounding during weeks or months of construction. As mentioned, the USP Sterie Compounding Committee beieves that it is reativey easy to convert an ISO Cass 8 buffer room to an ISO Cass 7 buffer room. However, the American Society for Heathcare Engineering (ASHE) states that converting ISO 8 to ISO 7 and requiring HEPA air fitration wi significanty increase the costs to design, construct, and operate the ventiation component of pharmacy buffer rooms, particuary if the design is to retrofit an existing ventiation system. They say increasing the air quaity from ISO Cass 8 to ISO 7 wi require substantiay greater air fow and cost (see Tabe 21-5.) Existing suppy fans to ceiing air gris may be insufficient to overcome the resistance of HEPA fiters, in which case hospitas must insta in-ine booster fans to maintain a positive pressure of the buffer area reative to the ante-area. 33 In ower voume faciities or for pharmacy night shift or sateite operations, pharmacists might consider instaing a compounding isoator in existing space. This is an option for ow and medium risk compounding ony. The CAI or CACI must meet USP Chapter <797> conditions to be considered for use outside an ISO Cass 7 buffer room, i.e. compete isoation from the surrounding room, minimum air partice counts in the direct compounding area and at the transfer door when the surrounding room. 1 See Chapter 4. If a CACI that meets the Chapter <797> requirements is used for compounding hazardous drugs outside an ISO 7 buffer area, it must be in a segregated compounding room that maintains a minimum negative pressure of 0.01-inch water coumn and have a minimum of 12 air changes per hour. 1 A non-iso 7 aternative for ow-risk compounding for sterie preparations with 12- hour or ess beyond-use dates is to create a segregated compounding area. Pacement of devices (e.g., computers, printers) and objects (e.g., carts, cabinets) that are not essentia to compounding in the segregated area shoud be imited, based on their effect on air quaity in the ISO Cass 5 primary engineering contro. 1 Architectura Schematic Pan Pharmacists shoud prepare pans with a hospita designer or architect in ine with the detaied specifications in the functiona program. For the hospita architect unfamiiar with ante-area/buffer area design, ISO Standard specifies the requirements for the design and construction of ante-area/buffer area faciities. 34 This standard is intended for use by purchasers, suppiers and designers of ante-area/buffer area instaations and Tabe Cost of Converting an ISO Cass 8 Buffer Room to an ISO Cass 7 Buffer Room* ISO Cass Ceiing Covered by Air Gris Approximate Cost of Ceiing Air Gris 8 5% 15% $50 per square foot 7 15% 20% $200 $250 per square foot *Source: Woodin D. Deputy Executive Director, American Society for Heathcare Engineering. Comments on summary of proposed revisions to <797>. usp797rev3.pdf Accessed February 4,

16 Compounding Sterie Preparations provides a checkist of important parameters of performance. Construction guidance is provided, incuding requirements for quaification and start-up activities. The pharmacist has the foowing roes in functiona panning 16 : 274 Derive pharmacy goas and objectives as to sterie compounding. Identify functions to be performed in the ante-area and buffer area. Determine workfow in the ante-area and buffer area. Determine the physica environment needed. Decide how to hande workoad during the renovation process. Specify requirements for the ante-area and buffer area: Workoad (e.g., average and maximum daiy numbers of parentera nutrition soutions, batches of syringes, chemotherapy compounding, peritonea diaysates, stat admixtures). Equipment types and numbers. Wi bioogica safety cabinets or isoators be exhausted to the outside (they shoud be)? Storage requirements for suppies and finished preparations. Personne types and numbers. Materias handing. Communication systems (e.g., intercom, emai, teephones, overhead paging). Services expected from other departments (e.g., IV soution deiveries, housekeeping). Security (e.g., ocked doors, access contro systems, video cameras). Utiities (e.g., ighting, eectrica outets, pumbing, computer ines.) Environmenta quaity contro (i.e., ISO Cass 5 or 7 or 8). Housekeeping and ceaning routines. Environmenta samping routines (e.g., aminar air-fow workbench testing, air and surface microbia counts, air particuate counts). Together the pharmacist and designer/architect find optima arrangements for work areas, find the best ocation, cacuate space and deveop tria schematics. The architect s roe is to transate a of this into architectura pans, i.e., determining how much square footage is needed, designing the ayout of the space, specifying construction materias, deveoping project budgets, producing bue prints and issuing change orders. The architect may be on the hospita staff, may be hired by the construction project or may be suppied by the construction company. Some hospita architects wi need to review recommended practices in ante-area/buffer area design. 35,36 Construction Contract Preparing the Request for Information (RFI) Before asking a vendor to bid on buiding an ante-area/buffer area, evauate potentia vendors by asking for information about their abiities and resources; soicit financias or Dun and Bradstreet reports and ask for a isting of recenty competed projects in faciities ike yours. Ca for references or visit some of these faciities. Ask the vendor to submit a set of design pans for a simiar project and resumes for the proposed project team. Seect three to five vendors to whom you wi submit a request for proposa. Handing the Request for Proposa (RFP) Together, the pharmacist and hospita engineer or architect shoud prepare the RFP and seect the potentia vendors most ikey to serve the faciity s needs. The request for proposa can foow these guideines 37 : 1. Suppy potentia vendors with pertinent information to meet the requirements but not so detaied as to stife their creativity. 2. Provide a genera overview of the faciity and its requirements, e.g., the type of work to be done, hours of operation. 3. Present the scope of work to be provided by the vendor, i.e., design, construction, eectrica, heating, ventiation, and air conditioning (HVAC), institutiona or vendor-suppied connections for eectrica, ventiation, gases, etc. James T. Wagner (author of Chapter 4) recommends that Type C HEPA fiters be used in pharmacy ante-area/buffer area air suppies. 38