MSHP/MHA Joint Comments and Recommendations for amending the Proposed 247 CMR 17.00 Regulations - Sterile Compounding
Pages 2-11 - Priority Areas of Concern
Comments submitted by Southcoast Hospitals group indicated in blue font.
Comments submitted by: Maria DeAbreu RPh, PharmD , Pharmacy Sterile Products Team Leader. Nov 29th, 2017.
Section / Draft / Recommendation / Evidence / Impact/NotesGeneral / 247 CMR 17 does not have a definition section / Include a definition section. The definitions should include but not be limited to biological material, stock solutions, equipment, etc. / CMR / A definition section is necessary to provide clarifications to the chapter for the end user.
17.03 (2) / A pharmacy may not pool or prepare stock solutions utilizing single dose vials to extend a beyond use date (BUD) beyond 6 hours after puncture within ISO Class 5 / Use current USP <797> Standards for a Medium Risk Product in the absence of sterility testing: BUD = 30 hours RT or 9 days Refrigerated OR use draft version of the 2015 USP <797> for a Category 2 product in the absence of sterility testing, no preservative added, prepared from sterile starting components BUD = 6 days RT or 9 days refrigerated / USP <797> / The regulationsdo not mention whether or not repackaging the contents of single dose vials into plastic syringes is allowed (batching), as in the case of National drug shortages? Will this follow Medium-risk compounding requirements? 9 days refrigerated or 30 hrs Room temperature BUD. Is this considered compounding or repackaging?
17.05 / A licensee shall prepare a non-hazardous, non-radiopharmaceutical, low risk level CSP with a 12 hour BUD at room temperature or 24 hour BUD refrigerated in an ISO Class 7 buffer room or an ISO Class 8 dedicated compounding room (“DCR”) equipped with a commercially manufactured PEC such as a LAFW or BSC and shall comply with all other provisions of 247 CMR 17.00, unless otherwise provided / Use current USP <797> Standards for a Low Risk Product in the absence of sterility testing BUD = 48 hours RT or 14 days Refrigerated
OR
Use draft version of the 2015 USP <797> for a Category 2 product in the absence of sterility testing, no preservative added, prepared from sterile starting components BUD = 6 days RT or 9 days refrigerated OR if products used have preservative added BUD = 28 days RT or 42 days refrigerated.
OR
Retain the 12hour BUD restriction but remove “in an ISO Class 7 buffer room or an ISO Class 8 dedicated compounding room (“DCR”)” and replace with “in a segregated compounding area, per USP 797 standards.”, / USP <797> / If left as written, pharmacy satellites will not be able to prepare ambulatory compounded sterile products such as allergens and anticipatory medications for infusion services, or anticipatory medications in procedural areas such as the OR or ED. A 12-hour BUD will inhibit allergy ambulatory clinics from giving their patients appropriate allergen therapy. See impact comments for 17.12
In USP 797, the use of a 12hr BUD for low-risk CSPs applies to medications compounded in a segregated compounding area. This 12hr BUD restriction is necessary because in an SCA, CSPs are compounded in a PEC, but there are not sufficient secondary engineering controls required to maintain ISO 8 or better air in the room. This is a suitable rule for satellite pharmacy areas that employ a hood for just in time compounding, such as in EDs and ORs.
If left as written, pharmacy satellites will not be able to prepare medications for patients and will need to revert to have the medications prepared by nursing or physician staff, this is a major step backwards in medication safety.
The massive costly renovations needed to convert satellites built as SCA into the new DCR definition are not only cost prohibitive and will cause significant downtimes for pharmacy operations, in many cases, the engineering changes are not possible to achieve within the hospital building.
17.06 (5) / A pharmacy may not compound a component of a CSP from API when a version of that component is commercially available. / Add the following verbiage "unless products are on the national drug shortage list". / FDA Drug Shortage Database / Considerations must be made for national drug shortage crisis where hospital pharmacies should be allowed to compound from API if critically necessary and for immediate use. As drafted, patient care is in jeopardy if hospital pharmacies are unable to provide lifesaving medications to their patients who are currently receiving care or have been scheduled for a service/procedure in the event of a national shortage.
17.07 / A BUD must be calculated from the time of compounding and shall include the time a drug will reside inside an implantable infusion pump reservoir. / Use current USP <797> prior to administration “When CSPs are likely to be exposed to warmer than 30° for more than 1 hour during their administration to patients, the maintenance of their sterility and stability should be confirmed from either relevant and reliable sources or direct testing.”
Use current USP definition of a Beyond-Use Date (BUD): The date after which a compounded preparation shall not be used; determined from the date the preparation is compounded. Remove “and shall include the time a drug will reside inside an implantable infusion pump reservoir” / CDC, Product Package Insert / It is not the industry standard to include the time the drug is inside the reservoir in the calculation of a beyond use date. This section could result in labeling that can easily be misinterpreted by the end user. If the end user is familiar with the standard BUD definition, they could think the drug is good for much longer than it is, leading to a significant risk for patient harm, including death from serious infection.
In addition, this creates unnecessary extra steps, time and effort that could impact patient care for products that do not need to be treated any differently than any other sterile compounded product.
17.09 (2) / The procedures for compounding CSPs using blood-derived or other biological material shall require compounding to be separate from routine material-handling procedures and must describe cleaning of PEC and other equipment used in CSP preparation to avoid cross-contamination. / Include definitions differentiating “blood-derived” and “other biological material” so substances such as insulin (biologically derived from animals) are not misinterpreted as being a biological material. / CDC, Product Package Insert / If left as written, a hospital pharmacy could have to follow extra steps, time and effort that could impact patient care for products that should not be treated any differently than any other sterile compounded product.
17.12 (1) / A Licensee may not conduct sterile compounding in a segregated compounding area that is not ISO classified / Use 2015 draft USP <797>: Segregated Compounding Areas: In some situations, a PEC may be located within an unclassified area, without a buffer or ante-area. This type of design is called a segregated compounding area. Category 2 CSPs must never be compounded in segregated compounding areas; only Category 1 CSPs can be compounded in facilities with such designs. / USP <797> / If left as written, hospital pharmacies will not be able to continue providing service to many ambulatory clinics and procedural areas. See impact comments for 17.05
It is critical to maintain the designation of segregated compounding areas in order to maintain safe medication practices currently provided by the ED and OR satellites in our facility. The alternative is to perform immediate use-compounding on a countertop with a 1 hour BUD. Clearly this is inferior to compounding the CSP inside a PEC. If left as written, hospitals are prohibited from using PECs anywhere outside of an ISO 8 or better room, even if they want to use it in a setting of immediate use compounding.
17.13 (3) / The air changes shall come from the HEPA filtered air. HEPA filtered air shall be introduced at the ceiling. Any air exchanges supplied to buffer room from the PEC must be in addition to the 30 ACPH. / Adjust to allow for the addition of PEC air in the calculation to be in line with USP 797 and current CETA guidelines / Current USP <797>
Proposed USP <797>
ASHP Sterile Compounding Guidelines.
CAG-008-2010 / Current and the proposed USP allows for the addition of PEC air in the calculation.
17.13 (4) / A pharmacy may not utilize any ISO classified area for both sterile and non-sterile compounding. / Adjust to a best practice with wording such as, Shouldnot routinely utilize ISO Class 5 areas for both sterile and non-sterile compounding without thoroughly cleaning between compounding sessions. / If left as written, satellite pharmacies that are built as DCRs, especially pediatric satellites, will be prohibited from compounding the non-sterile medications routinely needed for patients because they also compound CSPs in that room. In the setting of hazardous non-sterile compounding, such as hydroxyurea suspensions, the negative pressure classified area is the only alternative negative pressure area available to perform the non-sterile compounding. This will leave pharmacies with no options to provide medications to patients and meet NIOSH standards to keep employees safe.
I agree with the recommendation made by MSHP/MHA regarding the use of a shared use of the negative pressure BSC for hazardous non-sterile compounding in addition to hazardous sterile compounding. As long as there is a thorough disinfection (cleaning procedure) in between compounding sessions (sterile and non-sterile) , pharmacy personnel will be able to safely compound hazardous non-sterile compounds , especially in those pharmacy locations where there is limited space and an additional BSC for hazardous non- sterile compounding is not feasible.
17.3 (9d) / Beginning January 1, 2018, a pass-through shall:
(a) be constructed of a nonporous, smooth, non-shedding, impermeable material such as acrylic, polycarbonate or similar fiberglass-reinforced plastic, glass, or stainless steel;
(b) have a double interlocking door design;
(c) not have an opening larger than 4 square feet;
(d) be located between:
1. ISO Class 7 buffer room and ISO Class 8 area or better;
2. ISO Class 8 area to unclassified space or better; or
3. ISO Class 7 ante room to unclassified space or better;
(e) not be a refrigerator unit. / Adjust to “May be located between”, allowing pharmacies the ability to design a cleanroom environment that fits the needs and space of their organization, OR remove requirement of 1. ISO Class 7 buffer room and ISO Class 8 area or better / Requiring a pass-through between all classified spaces is unnecessary depending on the workflow and design of a pharmacy. Pass-throughs require a large amount of unusable space. In our facility, the workflow is such that a pharmacist moves between the classified areas to check the work of the technicians. This traffic pattern will not change with the addition of a pass-through. If left as written, the unnecessary required addition of a pass-through will encroach on valuable square footage in a space-constrained footprint.
17.13 (12) / A pharmacy shall validate at least once per year, with direct testing, the recovery time of each primary and secondary engineering controls for particle count, temperature, and humidity, following activities including personnel entering and exiting, gowning, staging, material transfer, compounding, labeling, cleaning, and testing. / Remove this from the regulation and instead make this a “Best Practice” or policy issued by the Board so that routine changes based on national standards can be adopted in a timelier manner outside the regulatory process. / FDA:GMP Standards
ISO-14644 / Semi-annual recertification of the PEC is used to determine the maintenance of functionality of the PEC. The functional recovery time of a PEC is almost immediate based on the hood volume and airflow, typically less than 1 minute. Recovery time of a SEC, though longer than a PEC, can be noted within the room recertification under dynamic operating conditions. A standard 30 minutes as stated in these regulations along with a 1 hour standard for SEC coupled with cleaning and disinfection procedures handled on a local policy level provides substantial safety for continuation of compounding. The addition of a continuity of care plan as stated in these regulations provides an outline for managing situations directly related to planned or unplanned interruptions of airflow.
17.13 (14) / A pharmacy may not locate a refrigerator, dishwasher, incubator, or other appliance in an ISO Classified area / Change to “any appliances that use running water (i.e. dishwasher) or used to promote microbial growth (i.e. incubator). / USP <797> / If left as written, this would be restricting innovation in pharmacy operations. Consideration has to be made for new technology and future needs: i.e. pass- throughs that are carousels (both refrigerated and non-refrigerated), robotics with cooling systems.
17.14 (1) / A pharmacy shall locate an ISO Class 5 PEC for non-hazardous drug compounding within a positive pressure ISO Class 7 buffer room or ISO Class 8 DCR. / Include, “or segregated compounding area”. Or use USP <797> 2015 language “A PEC used for compounding may be placed in an unclassified, segregated compounding area if only Category 1 CSPs are compounded in the PEC”. / USP <797> / If left as written, hospital pharmacies will not be able to continue providing service to many ambulatory clinics and procedural areas, such as ORs and EDs. See impact comments for 17.05 and 17.12 (1).
17.14 (5) / A pharmacy shall prepare CSPs in a commercially manufactured ISO Class 5 PEC. A pharmacy may not prepare CSPs in a vertically integrated ISO Class 5 workbench or ISO Class 5 open buffer room design. / Remove section entirely, or adjust to include USP <797> 2015 definition of a LAFS (Laminar airflow system). LAFS: Provides an ISO Class 5 or better environment for sterile compounding. A LAFS provides smooth, unidirectional HEPA-filtered airflow that is designed to prevent contamination of a sterile compounding environment. The LAFS can consist of either a
LAFW or a HEPA filter alone creating an ISO Class 5 zone within an ISO Class 7 room, as long as unidirectional airflow is maintained. / USP <797> / If left as written, organizations with this design will be prohibited from operating, forcing them to undergo significant and costly renovations, causing major interruptions in patient care. New expensive renovations recently opened in 2017 employs a LAFS open buffer room design and will be prohibited.
17.15 (1a) / Buffer Room
(a) A buffer room shall be at least 144 square feet. / Remove entirely the square footage requirement of 144 square feet or make substantial adjustments to a more practical minimum square foot standard like linear feet of hood space or removing entirely (e.g. 64 square feet + 8 square feet for every linear foot of hood over 8 feet). / Current USP <797>
Proposed USP <797>
ASHP Sterile Compounding Guidelines. / There is currently no standard for the size of a buffer room. The state of control is regulated by the HVAC, SEC and PEC, which are fined tuned to the size of the room built. The room should be built to the size needed to perform the necessary operations, and not be dependent on a fixed number. For example, one 3’ hood in a room this size vs five 4’ hoods and carts and staff and the supplies needed to support this implied volume of work. It is not evidence based to assume a pharmacy cannot demonstrate a state of control in a room of 130 square feet without an additional 14 square feet.
Consideration of the size of the buffer room must be based on the number of hoods that can be allowed in a specific space , equipment (carts, stools, racks) etc, number of people working in the area, as this directly affects the air quality of the classified space. A buffer room measuring 144 ft2 may either contain 3 laminar flow hoods within the same space , plus metal carts, personnel, equipment (technology- computer stations) as opposed to another facility that contains the same room size foronly 1 laminar flow hood, no more than 2 compounders at a time in the room and one metal cart. The difference in air quality and maintaining ISO 7 conditions in the room must be emphasized rather than focusing on determining a specific size for the space in the buffer area.
17.15 (2d) / Ante Room
(d) An ante room shall be at least 100 square feet. / Remove the requirements for specific square footage space requirement. / Current USP <797>
Proposed USP <797>
ASHP Sterile Compounding Guidelines. / There is currently no standard for the size of an ante room. The size of the room should be dependent on the work occurring within and the available space to implement a buffer room or cleanroom suite operation of a given size.
In agreement with the above recommendation.
17.15 (3f, g) / (f) A buffer space in a DCR shall include 40% of the square footage in the DCR.
(g) An ante space in a DCR shall:
1. include 60% of the square footage in the DCR; / Remove entirely the square footage requirement of
or make substantial adjustments to a more practical minimum square foot standard like linear feet of hood space + amount of reasonable space that a human body needs to work (e.g. Square footage occupied by the hood + 8 square feet for every linear foot). / Current USP <797>
Proposed USP <797>
ASHP Sterile Compounding Guidelines. / There is currently no standard for the size of a buffer or ante room. The size of the room should be dependent on the work occurring within and the available space to implement a buffer room or cleanroom suite. This section was newly incorporated into this draft, as an attempt to respond to previous comments about square footage. See impact comments for sections 17.15 (1a and 2d).