1. Introduction
1.3 Overview
(Line 50) “There is no acceptable level of personnel exposure to HDs.”
Suggestion: We suggest removing line 50.
Explanation: Laboratory and non-laboratory personnel are exposed to chemicals on a daily basis both in
and outside of the workplace. Within the workspace, acceptable levels are dictated by the Occupational
Safety and Health Administration (OSHA). By law, general industry workplaces (i.e. workplaces that are
not limited to Construction or Shipyards) must conform to OSHA 1910.1000 Toxic and Hazardous
Substances subpart Z. In this law, OSHA outlines Permissible Exposure Limits (PELs) that are acceptable
levels of exposure within the workspace. General industry workplaces must conform to OSHA
1910.1000 subpart Z.
By law, OSHA receives recommendations for setting PELs from the National Institute for Occupational
Safety and Health (NIOSH). NIOSH submits these recommendations to OSHA in the form of
Recommended Exposure Limits (RELs). Thus the proposed chapter uses a definition of Hazardous Drugs
(HDs) set and researched by OSHA and NIOSH respectively, but does not use their findings for said HDs
to set exposure limits.
In a blatant contradiction, the proposed chapter states that there is “no acceptable level of personnel
exposure to HDs” – all the while such levels exist, defined by law. Should USP wish to implement this
proposed chapter, we request that they present and publish data that supports this claim (and
fundamentally the purpose of implementing this proposed chapter) for all chemicals on the current
NIOSH list of Hazardous Drugs.
We urge that USP use the current OHSA published PEL values as a means of measuring acceptable levels
of exposure to NIOSH published hazardous drugs. If the committee feels that these levels (which are
law) are not stringent enough, we recommend that the committee refer to NIOSH’s RELs as acceptable
levels of exposure to NIOSH HDs.
Should these lists not include chemicals that the committee feels should be incorporated, we would like
to recommend referencing the American Conference of Governmental Industrial Hygienists (ACGIH), a
non-governmental organization that publishes acceptable levels of chemical exposure in the form of
Threshold Limit Value (TLV) data.
(Lines 50-52) “The processes listed in this chapter are intended to provide containment of HDs to as low
a limit as reasonably achievable (ALARA).”
Suggestion: It is suggested that lines 50-52 be amended to enforce containment to OSHA 1910.1000
Subpart Z, NIOSH RELs, and/or ACGIH TLVs.
Explanation: This sentence is in direct conflict with its predecessor in Line 50 in which the proposed
chapter states that there is “no acceptable level of personnel exposure to HDs.”
Within the workspace, acceptable levels are dictated by the Occupational Safety and Health
Administration (OSHA). By law, general industry workplaces (i.e. workplaces that are not limited to
Construction or Shipyards) must conform to OSHA 1910.1000 Toxic and Hazardous Substances subpart
Z. In this law, OSHA outlines Permissible Exposure Limits (PELs) that are acceptable levels of exposure
within the workspace. General industry workplaces must conform to OSHA 1910.1000 subpart Z.
By law, OSHA receives recommendations for setting PELs from the National Institute for Occupational
Safety and Health (NIOSH). NIOSH submits these recommendations to OSHA in the form of
Recommended Exposure Limits (RELs). Thus the proposed chapter uses a definition of Hazardous Drugs
(HDs) set and researched by OSHA and NIOSH respectively, but does not use their findings for said HDs
to set exposure limits.
In a blatant contradiction, the proposed chapter states that there is “no acceptable level of personnel
exposure to HDs” – all the while such levels exist, defined by law. Should USP wish to implement this
proposed chapter, we request that they present and publish data that supports this claim (and
fundamentally the purpose of implementing this proposed chapter) for all chemicals on the current
NIOSH list of Hazardous Drugs.
We urge that USP use the current OHSA published PEL values as a means of measuring acceptable levels
of exposure to NIOSH published hazardous drugs. If the committee feels that these levels (which are
law) are not stringent enough, we recommend that the committee refer to NIOSH’s RELs as acceptable
levels of exposure to NIOSH HDs.
Should these lists not include chemicals that the committee feels should be incorporated, we would like
to recommend referencing the American Conference of Governmental Industrial Hygienists (ACGIH), a
non-governmental organization that publishes acceptable levels of chemical exposure in the form of
Threshold Limit Value (TLV) data.
(Lines 52-53) “HDs shall be compounded in proper engineering controls, as defined in this chapter.”
Suggestion: This sentence should be removed or amended to read: “It is suggested that HDs be
compounded in proper engineering controls, as suggested in this chapter.”
Explanation: The “proper engineering controls,” as defined in USP 800, commonly contradict one
another. They also induce barriers to a functioning free market. They create such onerous financial
burdens as to push out most practitioners including: compounding pharmacies, outpatient clinics, long
term care facilities, hospital pharmacies, etc. These engineering measures are not only contradictory
and financially taxing, but they are unnecessary in light of today’s available technology and alternative
product solutions.
Our remaining comments are intended to point out where such discrepancies exist and where new
requirements are unnecessary, excessive, vague, or redundant.
At the least, the wording in lines 52-53 should be amended to the following: “It is suggested that HDs
be compounded in proper engineering controls, as suggested in this chapter.”
(Lines 109 – Table 2. Types of Devices for Compounding with HD) “Type of Compounding: Nonsterile.
Type of Device: Containment Ventilated Enclosure (CVE) or Class I Biological Safety Cabinets (BSC).”
Suggestion: We agree with the document’s wording in this case.
Explanation: For the purposes of Nonsterile HD Compounding, we agree that a CVE or Class 1 BSC as
defined in Appendix C: Types of Biological Safety Cabinets, lines 1288-1292 is appropriate. We agree
with the document’s wording in this case.
Lines 1288-1292 in this proposed standard define a Class 1 BSC with the following statement: “Class 1: A
BSC that protects personnel and the environment but does not protect the product/preparation.
Personnel protection is provided as a minimum velocity of 75 linear feet/min of unfiltered room air is
drawn through the front opening and across the work surface. The air is then passed through a
HEPA/ULPA filter either into the room or to the outside in the exhaust plenum, providing
environmental protection.”
Per Line 109, Table 2, a Class 1 BSC which meets the appendix C definition of a Class 1 BSC is appropriate
for use with Hazardous Drugs. This means that air that passes through a HEPA/ULPA filter back into the
room is acceptable. By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns
or larger with a 99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for
ULPA filters. Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of
HD powders. This option is appropriate, financially feasible, and provides necessary safety for
laboratory personnel compounding with Hazardous Drugs.
We agree with the document’s wording in line 109 and do not wish to amend the document here.
However, if upon reading the Appendix C definition of a Class I BSC, the committee no longer feels that
this type of device is appropriate for use, then we request that the USP 800 provide the community
with data to support this theory before imposing cost-prohibitive standards upon the industry that will
put many out of business.
4. Responsibilities of Personnel Handling HDS
(Lines 170-174) “Each entity shall have a compounding supervisor who is the designated individual
responsible for developing and implementing appropriate procedures; overseeing facility compliance
with this chapter and other applicable laws, regulations, and standards; ensuring competency of
personnel; and assuring environmental control of the compounding areas.”
Suggestion: We suggest changing the wording of the document “implementing appropriate procedures”
to “implementing USP 800-complaint procedures.” We also suggest that the “applicable laws,
regulations, and standards” to which the supervisor will be held accountable, should be explicitly stated.
Explanation: While this comment is an entirely reasonable expectation, the language used does not
designate the means of measuring what is “appropriate” procedure. Are said procedures limited strictly
to what is outlined in the USP 800 document? If so, the language should be amended to: “implementing
USP 800-compliant procedures.”
Furthermore, in the ever-changing compounding industry, we feel that the laws, regulations, and
standards to which compounders are held should be clearly defined. The proposed standard simply
states: “this chapter and other applicable laws, regulations, and standards…” All too often regulations
contradict one another and, as in the case of this proposed standard, often within the same regulation.
For the individual tasked with lines 170-174, the “applicable laws, regulations, and standards” to which
they will be held accountable, should be explicitly enumerated.
(Lines 186-189) “Individuals who are engaged in HD compounding shall be competent in HD
compounding and should continually expand their compounding knowledge by participating in
seminars, training programs, and/or studying appropriate literature.”
Suggestion: We suggest amending lines 186-189 to define the level of competency, assessment for
competency, and grace period to implement competency assessment per the explanation below.
Explanation: The proposed chapter claims that all individuals who are engaged in HD compounding
“shall be competent in HD compounding.” The intent of this line is reasonable. However, the standard
gives no definition of the required level of competency. The proposed chapter does not state how the
competency is defined, determined, or continually assessed.
For pharmacies wishing to continually employ a hazardous drug compounding individual while also
ensuring their compliance with lines 186-189, the proposed standard gives no means on how to achieve,
implement, or assess current or potential employees.
Furthermore, the proposed standard does not outline any time period after the standard is
implemented, during which pharmacies may have the chance to interpret this standard, assess
employee “competency,” and provide additional training to achieve the proposed standard’s undefined
level of “competency.”
(Lines 189-191) “They shall be knowledgeable in the contents of chapters (795), (797), and (1163), other
applicable USP chapters and General Notices and Requirements, and applicable federal and state laws,
regulations, and guidelines.”
Suggestion: We suggest explicitly stating all contents on which personnel shall be knowledgeable.
Explanation: The laws, regulations, and standards to which compounders are held should be clearly
defined. The proposed standard simply states: “…and applicable federal and state laws, regulations,
and guidelines.” All too often regulations contradict one another and as in the case of this proposed
standard, often within the same regulation. The “applicable laws, regulations, and standards” to which
the “supervisor” of line 170 will be held accountable, should be explicitly enumerated here in lines 186191.
5. Facility Design and Engineering Controls
5.1 General Guidance
(Lines 204-207) “Access to areas where HDs are stored and prepared shall be restricted to authorized
staff to protect persons not involved in HD handling. The location of the HD compounding area shall be
located away from break rooms and refreshment areas for staff, patients, or visitors to reduce risk of
exposure.”
Suggestion: We suggest explicitly defining separation requirements.
Explanation: The proposed standard requires that the compounding area shall be located “away” from
break rooms and refreshment areas, but gives no definition or measurement of how far apart these
areas must be. This makes it difficult for inspectors and pharmacists to implement this proposed
standard, leaving the matter to interpretation. Further, it is not stated if this “away” requirement
applies to areas where HDs are stored and prepared.
(Lines 207-213) “Signs designating the hazard shall be prominently displayed before entry into the HD
area.
Separate designated areas shall be available for (see Appendix D):
 Unpacking HDs
 Nonsterile HD compounding (if performed by the entity)
 Sterile HD compounding (if performed by the entity)
Designated HD handling areas shall be segregated from non-HD areas.”
Suggestion: We suggest explicitly defining separation requirements.
Explanation: Similar to the comment above, the proposed standard requires that the HD compounding
area shall be “segregated” from non-HD areas, without giving definition to the term “segregated.” This
makes it difficult for inspectors and pharmacists to implement this proposed standard, leaving the
matter to interpretation.
(Lines 221-223) “A laminar air flow workbench (LAFW) or compounding aseptic isolator (CAI) shall not be
used for the compounding of an HD.”
Suggestion: We do not wish to amend the document here.
Explanation: We agree and support this statement.
(Lines 227-228) “When asepsis is not required, a Class I BSC, CVE, or an isolator intended for
containment applications may be sufficient.”
Suggestion: We agree with the document’s wording in this case.
Explanation: For the purposes of Nonsterile HD Compounding, when asepsis is not required, we agree
that a CVE, an isolator intended for containment applications, or a Class 1 BSC as defined in Appendix C:
Types of Biological Safety Cabinets, lines 1288-1292 is appropriate. We agree with the document’s
wording in this case.
Lines 1288-1292 in this proposed standard define a Class 1 BSC with the following statement: “Class 1: A
BSC that protects personnel and the environment but does not protect the product/preparation.
Personnel protection is provided as a minimum velocity of 75 linear feet/min of unfiltered room air is
drawn through the front opening and across the work surface. The air is then passed through a
HEPA/ULPA filter either into the room or to the outside in the exhaust plenum, providing
environmental protection.”
Per Line 227-228, a Class 1 BSC which meets the appendix C definition of a Class 1 BSC is appropriate for
use with Hazardous Drugs. This means that air that passes through a HEPA/ULPA filter back into the
room is acceptable. By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns
or larger with a 99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for
ULPA filters. Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of
HD powders. This option is appropriate, financially feasible, and provides necessary safety for
laboratory personnel compounding with Hazardous Drugs.
We agree with the document’s wording in line 227-228 and do not wish to change the document here.
However, if upon reading the Appendix C definition of a Class I BSC, the committee no longer feels that
this type of device is appropriate for use, then we request that the USP 800 provide the community
with data to support this theory before imposing cost-prohibitive standards upon the industry that will
put many out of business.
5.2 Storage of HDs
(Lines 237-241) “Unless the HDs already exist in their final unit dose or unit-of-use packaging, HDs shall
be stored separately from other inventory in a manner to prevent contamination and personnel
exposure, which includes storage in a negative pressure room with at least 12 air changes per hour
(ACHPH). Depending upon pharmacy design, HD storage within the HD buffer area can fulfill this
storage criterion.”
(Lines 242-246) “Refrigerated HDs shall be stored in a dedicated refrigerator in the HD storage room,
buffer room, or containment segregated compounding area (C-SCA). In a containment secondary
engineering control (C-SEC) used for sterile preparations, an exhaust located adjacent to the
refrigerator’s compressor and behind the refrigerator should be considered.”
(Lines 247-252) “HDs shall be stored at or below eye level, in containers that minimize the risk of
breakage and leakage, and shall not be stored on the floor. Areas prone to specific types of natural
disasters (e.g., earthquakes) shall ensure that storage meets applicable safety precautions, such as
secure shelves with raised front lips. Storage of sterile and nonsterile HDs may be intermingled. HD
storage in sterile compounding buffer area shall be limited to those used for sterile compounding (see
chapter (797)).”
Suggestion: We request that the statement in lines 239-240 be removed: “which includes storage in a
negative pressure room with at least 12 air changes per hour (ACPH)” or amended to include the option
of HD storage in a ductless filtered cabinet. We also request that the required areas for unpacking and
storing HDs and non-HDs be reevaluated.
Explanation: As the standard is currently written, it can be interpreted as every facility (pharmacy,
outpatient clinics, long term care facilities, etc.) needing 6 total separate, designated areas for drug
unpacking and storage.
Areas for Unpacking
1. (Line 210) Unpacking of HDs.
2. (Line 213) Unpacking of non-HDs (since HD and non-HD handling areas must be separate).
Areas for Storing
3. (Lines 237-241) Storing non-refrigerated HDs in a negative pressure HD storage room.
(Lines 250-251) This area includes sterile and non-sterile, non-refrigerated HDs.
4. (Line 242) Storing of refrigerated HDs in a dedicated refrigerator. (Lines 250-251) This
refrigerator will store sterile and non-sterile, refrigerated HDs. (Lines 237-241) These
refrigerated HDs shall be stored in a separate negative pressure HD storage room.
5. (Lines 237-238) Storing of non-refrigerated non-HDs in a separate area altogether from HD
storage areas.
6. (Line 242) Storing of refrigerated non-HDs since they must be kept separate from
refrigerated HDs.
HDs should be treated appropriately and safely, but we must consider the environments in which HDs
are used. Many businesses (pharmacy, outpatient clinics, long term care facilities, etc.) have neither the
space nor the means for the renovations required to meet the proposed standard to simply unpack and
store hazardous drugs.
Furthermore, many facilities would shut down due to not having enough space to divide up in an effort
to implement the proposed requirements. This requirement will be especially damaging to existing
compounding pharmacies, outpatient clinics, and pharmacies within hospitals. As a result of facility
closure, access to necessary drugs will become especially limited. Ultimately, this proposed chapter
will do a disservice to the patient and the healthcare industry as a whole.
These space designations should be combined in an effort to minimize the renovations necessary for
businesses to continue operation. For example:
Could non-Hazardous and Hazardous drugs be unpacked in the same area? (Line 213 would
need to be removed).
Or, could non-sterile HD and non-HDs be stored in the same room with the presence of certain
physical barriers (i.e. a dedicated storage cabinet for non-sterile HDs with clear markings)?
(Lines 213, 237-238 would need to be revised).
Could HD and non-HDs be stored in the same refrigerator if HDs were kept within a physical
barrier within the refrigerated space (i.e. a dedicated box or cabinet within the refrigerator)?
(Lines 213, 242, 250-251 would need to be revised).
It is our primary business to promote the safe handling of drugs; however this requirement puts a heavy
financial burden on the industry to create handling areas that are excessive for the safe handling
practice that this standard is trying to embody.
External Venting for the Storage of HDs:
We start with lines 237-240 requiring the storage room for HDs to be externally ventilated. It is not
possible for certain businesses to meet the requirement in its current form for a number of reasons. To
begin, this requirement may be impossible to put into practice for many compounding locations that do
not own the building of their business location. Those spaces may not allow them to create structural
changes to their location simply for drug storage, thus potentially putting them out of business.
Even if ownership of space exists, and external ventilation is feasible, externally ventilating a room can
cost approximately $1,000 per every ten feet of ductwork installed. This does not account for the cost
of the blower on the roof (roughly another $2,000 USD) nor does this cost include the electricity cost to
continuously run the blower (required by the proposed standard- line 422).
It should be noted that this estimate per 10’ of ductwork is only for those labs that have straight line,
direct access to the external environment. For labs where ductwork needs to turn at a 90-degree angle,
additional charges will be incurred for each turn required of the ductwork to reach the roof from the
point of room ventilation.
In addition, this estimate does not take into account the additional ductwork (see costs above) and cost
of additional HVAC systems to create the make-up air necessary to meet the 12 ACPH required by the
proposed USP 800 standard. Typically one air-conditioning unit can range from $6,000-$12,000 USD.
Multiple HVAC make-up air-conditioning units might be required depending on room size. It should be
noted that this cost doesn’t include the energy charges associated with heating and cooling make-up air
before it is expelled to the external environment.
Because the standard requires that this system pull continuously, we must consider the increased
energy costs incurred in order to heat and cool this make-up air. Without knowledge of the size of each
storage room, a typical HVAC system pulling to give a 10’ x 10’ room at least 12 ACHPH, costs
approximately $5000 USD per year to run (of course costs will raise and lower slightly due to a change in
kWh per location).
Again, these costs are estimates to meet the requirement on lines 237-240 that all HD storage areas
should be externally ventilated. These are not small costs as they require extensive remodeling.
These costs will generate anti-competitive market forces barring entry to smaller businesses and put
many existing companies out-of-business.
Finally, the committee should understand that in many cases, external venting is simply not feasible.
The most common reason for a lack of external vent access is due to building design itself. In many
cases, the facility cannot be retrofitted to allow for additional ductwork without compromising building
infrastructure. This is commonly the case in older buildings or buildings with multiple floors, affecting
many hospital pharmacies.
In other cases, the building HVAC alone has led to what is called “Sick Building Syndrome” (SBS) and
access has been closed off to labs. The term “Sick Building Syndrome” refers to situations in which
acute health issues have arisen as a result of time spent in a particular building. In laboratories and
compounding pharmacies, SBS arises as a result of an improper balance in lab ventilation and make-up
air. Typically, not enough air is pumped into the lab for the blower to pull the proper amount of air
through exhaust ductwork. As a result, containment is lost and occupants within the building suffer the
consequences.
If the committee feels strongly that storage of HDs is inappropriate in an area without ventilation, we
would like to suggest a safe, and cost-effective alternative solution. Ductless filtered cabinets are
common in the marketplace, and offer the user protection from HDs during storage.
Ductless filtered cabinets operate the same as Class I BSC enclosures by providing personnel and
environment protection. These cabinets achieve this by drawing in laboratory air to the cabinet space,
and then passing cabinet air through a HEPA (or ULPA) filter, before pushing filtered air back into the
room.
By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns or larger with a
99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters.
Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders
from within a cabinet space.
Ductless filtered cabinets recirculate room air and thus, cost only about $200 annually in utilities. These
cabinets require no installation, no ductwork, and no renovation to the laboratory space. They provide
pharmacies with the ability to grow in space, or change designs since the cabinet and filtration system
are typically one unit and can be moved.
In regards to safety, ductless filtered storage cabinets can avoid the pitfalls of HVAC systems (i.e. Sick
Building Syndrome), by providing real-time filter monitoring, airflow monitoring, with audible and visual
alarms to alert the user in the event of unsafe conditions. Without the same burdens and potential
pitfalls associated with whole-room ventilation, ductless filtered storage cabinets are more readily
adopted and implemented in the workplace.
Finally, ductless filtered storage cabinets are more easily containment tested and challenge tested to
ensure proper safety conditions are being met. By performing third-party containment tests the user
can be assured that HDs are being confined to the interior space of the cabinet. By performing thirdparty particle-count challenge tests on post-filtered air, the user can be assured that HDs are being
properly caught by the HEPA/ULPA filter.
Ductless filtered storage cabinets are a realistic, feasible, cost-effective, testable, and safe alternative to
externally vented storage rooms.
Therefore, we request that the statement in lines 239-240 “which includes storage in a negative
pressure room with at least 12 air changes per hour (ACPH),” be removed or amended to include the
option of HD storage in a ductless filtered cabinet.
External venting of Containment Primary and Secondary Engineering Controls are evaluated below.
5.3 Engineering Controls
5.3.1 Background
(Lines 256-262) “Within this chapter, engineering controls are divided into three categories representing
primary, secondary, and supplementary levels of control (see Appendix A and Appendix C for more
details). C-PECs provide the environment at the point of use and are integrated into the C-SEC (i.e.
room). The C-SEC supports the C-PEC. Supplemental engineering controls are adjunct controls [e.g.,
closed-system drug-transfer device (CSTD)] used in conjunction with primary and secondary control
strategies.”
(Lines 263-266) “HDs that require alteration shall be manipulated (mixed, diluted, compounded, and
others) in a C-PEC in an area that is physically separated from other preparation areas, that is under
negative pressure, and has at least 12 ACPH. Additional criteria are listed below.”
5.3.2 Containment Primary Engineering Controls
(268-269) “All C-PECs shall be externally vented and place in a restricted access segregated room with
has a minimum negative pressure of 0.01 inches of water column.”
Suggestion: We request that the statement in lines 263-266 be changed to read: “HDs that require
alteration shall be manipulated (mixed, diluted, compounded, and others) in an approved C-PEC.” We
request that lines 268 – 269 be removed or amended to include the option of Class I BSC, including
single-stage or two-stage HEPA/ULPA filtered ductless enclosures.
Explanation: While we recognize and agree with USP’s attempt to create a safer environment for
pharmacists and technicians working with HDs, we feel that the current standard creates unrealistic
expectations for working environments.
First and foremost, it should be understood that an externally ventilated enclosure is not possible for a
majority of pharmacies that work with HDs. As previously stated, many small compounding businesses
have neither the space nor the means necessary for the renovations required to meet the proposed
standard in its current form.
In regards to externally venting the C-SEC:
It is not possible for certain businesses to meet the requirement in its current form for a number of
reasons. To begin, this requirement may be impossible to put into practice for many compounding
locations that do not own the building of their business location. Those spaces may not allow them to
create structural changes to their location simply for drug storage, thus potentially putting them out of
business.
Even if ownership of space exists, externally ventilating a room can cost approximately $1,000 per every
ten feet of ductwork required. This does not account for the cost of the blower on the roof (roughly
another $2,000 USD) nor does this cost include the electricity cost to continuously run the blower
(required by the proposed standard- line 422).
It should be noted that this estimate per 10’ of ductwork is only for those labs that have straight line,
direct access to the external environment. For labs where ductwork needs to turn at a 90-degree angle,
additional charges will be incurred for each turn required of the ductwork to reach the roof from the
point of room ventilation.
In addition, this estimate does not take into account the additional ductwork (see costs above) and cost
of additional HVAC systems to create the make-up air necessary to meet the 12 ACPH required by the
proposed USP 800 standard. Typically one air-conditioning unit can range from $6,000-$12,000 USD.
Multiple HVAC make-up air-conditioning units might be required depending on room size. It should be
noted that this cost doesn’t include the energy charges associated with heating and cooling make-up air
before it is expelled to the external environment.
Because the standard requires that this system pull continuously, we must consider the amount by
which each lab’s energy bill will increase in order to heat and cool this make-up air. Without knowledge
of the size of each storage room, a typical HVAC system pulling to give a 10’ x 10’ room at least 12
ACHPH, costs approximately $5000 USD per year to run (of course costs will raise and lower slightly due
to a change in kWh per location).
Again, these costs are estimates to meet the requirement on lines 263-266 that all HD storage areas
should be externally ventilated. These are not small costs as they require extensive remodeling.
These costs will generate anti-competitive market forces barring entry to smaller businesses and put
many existing companies out-of-business.
Finally, the committee should understand that in many cases, external venting is simply not feasible.
The most common reason for a lack of external vent access is due to building design itself. In many
cases, the facility cannot be retrofitted to allow for additional ductwork without compromising building
infrastructure. This is commonly the case in older buildings or buildings with multiple floors, affecting
many hospital pharmacies.
In other cases, the building HVAC alone has led to what is called “Sick Building Syndrome” (SBS) and
access has been closed off to labs. The term “Sick Building Syndrome” refers to situations in which
acute health issues have arisen as a result of time spent in a particular building. In laboratories and
compounding pharmacies, SBS arises as a result of an improper balance in lab ventilation and make-up
air. Typically, not enough air is pumped into the lab for the blower to pull the proper amount of air
through exhaust ductwork. As a result, containment is lost and occupants within the building suffer the
consequences.
Therefore, we request that the statement in lines 263-266 be changed to read: “HDs that require
alteration shall be manipulated (mixed, diluted, compounded, and others) in an approved C-PEC.”
In regards to externally venting the C-PEC:
Similar to the requirement for external venting C-SEC areas, external venting of all C-PEC’s may not be
attainable for all compounding pharmacies. For example, not all pharmacies own their physical place of
business. This may force pharmacies (outpatient clinics, long term care facilities, etc.) to close
unnecessarily due to a C-PEC requirement that cannot be physically met. Furthermore, this regulation
puts an unrealistic monetary requirement upon pharmacies dealing with HDs that may be able to
externally vent their C-PEC, but may not be able to fiscally afford to do so.
For example, in order to externally ventilate a 4’ enclosure at 100 lfpm for a typical workweek, the
pharmacy will be required to pay not only for the enclosure, but for its installation, ductwork, bends in
ductwork, blower requirements, make-up HVAC air, and electricity costs associated with heating and
cooling that make-up air. These costs are explained above, but can be estimated at approximately:
$5,000 per enclosure, $1,000 per 10’ of straight ductwork, $2,000 per required blower, $6,000-$12,000
for make-up air-conditioning systems, and $5,000 - $7,000 per enclosure for heating and cooling costs
associated with make-up air. These estimates are per enclosure, and do not include bends in ductwork,
nor electricity costs associated with running the blower.
Please note, these costs should be multiplied for the number of enclosures the pharmacy requires.
While our company promotes responsible handling and personal protection precautions for HD use, we
feel that the requirement of externally ventilating the C-PEC is unnecessary. If other C-PEC solutions did
not exist in today’s marketplace, we would gladly recommend and provide all of our customers with
externally ventilated enclosures. With recognition that we do manufacture (and will gladly provide
customers with) externally ventilated enclosures, we feel that this is excessive for the given application.
By design, HEPA/ULPA filters simply filter to a standard. These standards are 0.3 microns or larger with
a 99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters.
Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders.
Should the USP 800 committee feel that HEPA or ULPA filtration is not appropriate for capture of
powdered HDs, we ask that they provide the community with data to support this theory before
imposing cost-prohibitive standards upon the industry that will put many out of business.
Ductless enclosures with single-pass and dual-pass designs have been tested and certified by third
parties as appropriate for use with HDs, APIs, etc. In addition, HEPA/ULPA filtered ductless designs
are typically cheaper than the externally ventilated enclosure and only cost approximately $200
annually in utilities, require no ductwork whatsoever, no installation whatsoever, and are found to be
as safe as, or safer, than HEPA-filtered externally vented enclosures, as shown below.
HEPA/ULPA filtered Ductless Enclosures vs. HEPA-filtered Externally Ventilated Enclosures
In order to provide the USP committee with thorough consideration of the safety of the HEPA-filtered
Externally Ventilated Enclosure design, we would like to compare this design to the HEPA/ULPA filtered
ductless design available on the market. We would like the committee to understand that AirClean
Systems is happy to provide the market with either design. We will gladly manufacture to the proposed
USP-800 standard. However, the committee should understand the inherent flaws associated with
HEPA/ULPA-filtered Externally Ventilated Enclosures, that single-stage and two-stage HELPA/ULPA
filtered ductless enclosures were designed to overcome.
Filter Changes:
To begin, the proposed USP 800 does not address filter changes on their HEPA/ULPA C-PEC design. How
will the user safely change filters when they have reached their maximum capacity? The committee
should understand that when a user goes to change the HEPA/ULPA filter in an externally vented
enclosure, they will typically need to turn the enclosure off (powering down the roof blower as well). At
this point, the user will lose all negative pressure within the enclosure and ductwork. Thus they risk
exposure to powders that remain in the enclosure, the inside of the exhaust plenum, ductwork, and
even on the HEPA/ULPA filter itself.
Given the exposure risk, the committee will need a protocol for this. Said protocol would need to:
evacuate the lab, outline appropriate biohazard suit procedures, enumerate procedures for powering
HEPA/ULPA filtered externally ventilated enclosures, changing the HEPA/ULPA filter, turning on said
enclosures, testing for proper airflow, and then allowing workers back into the lab. Such a protocol
would be burdensome and difficult to delineate.
In comparison, two-stage ductless designs can be left on while the user changes out their
primary HEPA/ULPA filter. The secondary HEPA/ULPA filter provides constant protection as
they remove the used HEPA/ULPA filter, bag it inside the unit, and insert a new primary
HEPA/ULPA filter.
This design requires no lab evacuation, no enclosure shutdown, no airflow test, and no lab
personnel or patient disruption. Thus saving time, money, and minimizing the potential for
HD exposure. Furthermore, it is much more likely that proper filter change protocol will be
followed with two-stage ductless designs than in HEPA/ULPA externally vented enclosures.
Filter Alarms:
In addition, even if a user of a HEPA/ULPA filtered externally ventilated enclosure did follow the proper
protocol to change their filter (i.e. they evacuated the lab, re-entered the lab wearing a biohazard suit,
turned off all HEPA/ULPA filtered externally ventilated enclosures, changed the HEPA/ULPA filter, turned
on all said ventilated enclosures, tested for proper airflow, and then allowed workers back into the lab) -- how would they know when to change said filter?
The committee should understand that many total exhaust enclosures are not equipped with
HEPA/ULPA filter change alarms. In some cases, externally vented hoods may be equipped with manual
indicators in the form of additional mini or magna helic pressure gauges that display the pressure
differential across the HEPA/ULPA filter in the exhaust plenum. However, rarely do consumers fully
understand how to read and interpret these gauges. The proposed standard neither outlines a
procedure for such case, nor does the standard provide a means of testing user knowledge on reading
manual gauges as indicators of filter expiration.
At face value, HEPA/ULPA filter changes don’t seem that critical in externally vented enclosures.
However, if a HEPA/ULPA filter becomes clogged in an externally vented enclosure, then the blower
won’t be able to pull sufficient air through the unit. The user will lose negative pressure airflow.
Without proper air flow into the enclosure, containment is lost and the user will be exposed to HDs.
In comparison, single-stage and two-stage HEPA/ULPA filtered ductless enclosures are often
equipped with electronic filter change alarms. Electronic alarms remove the human factor
error associated with reading manual indicator gauges. These alarms constantly monitor the
HEPA/ULPA filter and audibly and visually alert the user when the filter is clogged. At this
point, the user may remove the HEPA/ULPA filter and replace it with a new one.
Unlike the HEPA/ULPA filtered externally vented enclosure, the user of a single-stage and twostage HEPA/ULPA filtered ductless enclosure immediately knows when their filter has become
clogged and is in need of replacement.
Airflow Issues:
When externally vented enclosures encounter airflow problems the user often does not know. The
reason is due to a lack of proper airflow monitors and blower controls. Often times increased sash
height, equipment location on the workbench, and even the number of enclosures pulling in the HVAC
system can lead to lowered, unsafe airflow levels in enclosures.
Simply put: why do chemistry labs stink? The externally ventilated enclosures aren’t maintaining proper
airflow. Were proper airflow maintained, air would never escape the front of an enclosure, and
technically speaking a lab space would smell no different than any other space in a building.
Though enclosures may be “inspected” once a year – sash height, equipment location within enclosure
space, and even personnel working at the face of the enclosure can change on a daily or even constant
basis. Each of these will affect airflow. Externally ventilated enclosures are not usually equipped with
variable speed blowers. Without said blowers, the enclosure cannot adjust speed to real-time enclosure
conditions. Why not? Most externally ventilated enclosures are designed for multiple enclosures to
hook into the HVAC ductwork.
However, the more enclosures that are connected to one blower, the lower the airflow will be in
enclosures furthest away from said blower. Externally ventilated enclosures try to combat this issue by
providing the user with vaneometers. These “controls” work off of a tissue-paper design -- if the paper,
or “indicator,” is being pulled in, airflow is heading into the unit.
With use of any manual face velocity indicator, the safety of the lab relies upon untrained individuals to
interpret already imprecise methods of measuring airflow to determine continued containment. As you
may assume, linking user safety to the stagnancy and intelligence of a simple piece of material is not
only flawed, but dangerously negligent. Will the committee, therefore, draft a protocol for testing of
airflow, and HEPA/ULPA filter efficiency of an externally ventilated enclosure?
While airflow may be flowing into an enclosure, OSHA regulations state that a minimum of 60 linear feet
per minute should flow into the enclosure to maintain negative pressure. In an ever-changing lab
environment, only true, real-time variable-speed blowers ensure that proper airflow is maintained
within each, individual enclosure space. However, since many externally ventilated enclosures work off
of a multiple unit to one-blower system, this is impossible since multiple variables change across each
enclosure in the lab.
In comparison, single-stage and two-stage filtration ductless enclosures work off of a oneenclosure one-blower system. With use of variable-speed blowers, the unit maintains proper
levels of airflow entering the workspace. In the unlikely event that airflow levels ever dip
below safe, pre-determined values (OSHA 19.10 states 60-120 linear feet per minute), proper
airflow monitors and controls will alert the user.
These safety precautions are absolutely necessary in providing the market with the highest
level of safety available. We would like to remind the committee that HEPA and ULPA filters
are built to a standard. These standards are 0.3 microns or larger with a 99.997% efficiency
for HEPA filters and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters. Given
that powdered HDs are caught by a HEPA filter (and certainly an ULPA filter), we believe users
have a right to use a ductless option in the lab with HDs and non-HDs.
Finally, ductless filtered enclosures are more easily containment tested and challenge tested
to ensure proper safety conditions are being met. Furthermore, by performing third-party
containment tests the user can be assured that HDs are being confined to the interior space of
the enclosure. By performing third-party particle-count challenge tests on post-filtered air,
the user can be assured that HDs are being properly caught by the HEPA/ULPA filter.
Many businesses (pharmacy, outpatient clinics, long term care facilities, etc.) have neither the space nor
the means for the renovations required to meet the proposed standard in its current form. As a result,
many facilities would be forced to shut down. This requirement will be especially damaging to existing
compounding pharmacies, outpatient clinics, and pharmacies within hospitals. As a result of facility
closure, access to necessary drugs will become especially limited. Ultimately, this proposed chapter
will do a disservice to the patient and the healthcare industry as a whole.
Therefore, we urge that both single-stage and two-stage HEPA filtered Class 1 BSC cabinets be
appropriate for use with HDs as already permitted according to lines 109, 227-228, & 281-282 as defined
in Appendix C (lines 1288-1298). Since ductless variations, that push contaminated air through a twostage HEPA/ULPA filtration process, are common, we believe that at the very least, these enclosures
should be accepted as C-PECs without the requirement of external exhaust.
Therefore we request that lines 268 – 269 be removed or amended to include the option of Class I
BSC, including single-stage or two-stage HEPA/ULPA filtered ductless enclosures.
5.3.3 Containment Secondary Engineering Controls
(Lines 271-272) “HD compounding activities must occur within a C-SEC where any C-PEC shall be vented
to the outside air through high efficiency particle air (HEPA) filtration.”
Suggestion: We request that lines 271-272 be removed or amended to include the option of Class I BSC,
including single-stage or two-stage HEPA/ULPA filtered ductless enclosures.
Explanation: When asepsis is not required, we agree with lines 109, 227-228 & 281-282 that a CVE, an
isolator intended for containment applications, or a Class 1 BSC as defined in Appendix C: Types of
Biological Safety Cabinets, lines 1288-1292 is appropriate.
Lines 1288-1292 in this proposed standard define a Class 1 BSC with the following statement: “Class 1: A
BSC that protects personnel and the environment but does not protect the product/preparation.
Personnel protection is provided as a minimum velocity of 75 linear feet/min of unfiltered room air is
drawn through the front opening and across the work surface. The air is then passed through a
HEPA/ULPA filter either into the room or to the outside in the exhaust plenum, providing
environmental protection.”
Per Lines 109 & 227-228, a Class 1 BSC which meets the appendix C definition of a Class 1 BSC is
appropriate for use with Hazardous Drugs. This means that air which passes through a HEPA/ULPA filter
back into the room is acceptable. However, the proposed standard states in lines 271-272 that the CPEC “shall be vented to the outside air.” This contradicts previous lines (109 & 227-228) which allow a
Class 1 BSC and later lines (1288-1292) that define a Class 1 BSC.
By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns or larger with a
99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters. Thus,
a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders.
A Class 1 BSC is appropriate, financially feasible, and provides necessary safety for laboratory personnel
compounding with Hazardous Drugs. We request that lines 271-272 be amended to allow for all
approved C-PECs. For example: “HD compounding activities must occur within an approved C-PEC and
C-SEC.”
Why Should a Ductless Class 1 BSC be appropriate for use with powdered HD Compounding?:
As previously stated in the comment section for lines 267-269; “While we recognize and agree with
USP’s attempt to create a safer environment for pharmacists and technicians working with HDs, we feel
that the current standard creates unrealistic expectations for working environments. First and
foremost, it should be understood that an externally ventilated enclosure is not possible for a majority
of pharmacies that work with HDs. As previously stated, many small compounding businesses have
neither the space nor the means necessary for the renovations required to meet the proposed standard
in its current form.
Similar to the requirement for external venting of HD storage areas, external venting of all C-PEC’s may
not be attainable for many compounding pharmacies. For example, not all compounding locations own
the building of their business location. This may force pharmacies (outpatient clinics, long term care
facilities, etc.) to close unnecessarily due to a C-PEC requirement that cannot be met. Furthermore, this
regulation puts an unrealistic monetary burden upon pharmacies dealing with HDs that may be able to
externally vent their C-PEC, but may not be able to bear the fiscal consequences.
For example, in order to externally ventilate a 4’ enclosure at 100 lfpm for a typical workweek, the
pharmacy will be required to pay not only for the enclosure, but for its installation, ductwork, bends in
ductwork, blower requirements, make-up HVAC air, and utility costs for heating and cooling make-up
air. These costs are explained above, but can be estimated at approximately: $5,000 per enclosure,
$1,000 per 10’ of straight ductwork, $2,000 per required blower, $6,000-$12,000 for make-up airconditioning systems, and $5,000 - $7,000 per enclosure for heating and cooling costs associated with
make-up air. These estimates are per enclosure, and do not include bends in ductwork, nor utility costs
associated with running the blower.
Please note, these costs should be multiplied for the number of enclosures the pharmacy requires.
While our company promotes responsible handling and personal protection precautions for use with
HDs, we feel that the requirement of externally ventilating the C-PEC is unnecessary. If other C-PEC
solutions did not exist in today’s marketplace, we would gladly recommend and provide our customers
with externally ventilated enclosures. With recognition that we do manufacture (and will gladly provide
customers with) externally ventilated enclosures, we feel that this is excessive for the given application.
By design, HEPA/ULPA filters simply filter to a standard. These standards are 0.3 microns or larger with
a 99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters.
Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders.
Should the USP 800 committee feel that HEPA or ULPA filtration is not appropriate for capture of
powdered HDs, we ask that they provide the community with data to support this theory before
imposing cost-prohibitive standards upon the industry that will put many out of business.
Ductless enclosures with single-pass and dual-pass designs have been tested and certified by third
parties as appropriate for use with HDs, APIs, etc. In addition, HEPA/ULPA filtered ductless designs
are typically cheaper than the externally ventilated enclosure and only cost approximately $200
annually in utilities, require no ductwork whatsoever, no installation whatsoever, and are found to be
as safe as, or safer, than HEPA-filtered externally vented enclosures, as shown below.
HEPA/ULPA filtered Ductless Enclosures vs. HEPA-filtered Externally Ventilated Enclosures
In order to provide the USP committee with thoughtful consideration of the safety of the HEPA-filtered
Externally Ventilated Enclosure design, we would like to compare this design to the HEPA/ULPA filtered
ductless design available on the market. We would like the committee to understand that AirClean
Systems is happy to provide the market with either design. We will gladly manufacture to the proposed
USP-800 standard. However, the committee should understand inherent flaws associated with
HEPA/ULPA-filtered Externally Ventilated Enclosures that single-stage and two-stage HELPA/ULPA
filtered ductless enclosures were designed to overcome.
Filter Changes:
To begin, the proposed USP 800 does not address filter changes on their HEPA/ULPA C-PEC design. How
will the user safely change filters when they have reached their maximum capacity? The committee
should understand that when a user goes to change the HEPA/ULPA filter in an externally vented
enclosure, they will typically need to turn the enclosure off (powering down the roof blower as well). At
this point, the user will lose all negative pressure within the enclosure and ductwork. Thus they risk
exposure to powders that remain in the enclosure, the inside of the exhaust plenum, ductwork, and
even on the HEPA/ULPA filter itself.
Given the exposure risk, the committee will need a protocol for this. Said protocol would need to:
evacuate the lab, outline appropriate biohazard suit procedures, enumerate procedures for powering
HEPA/ULPA filtered externally ventilated enclosures, changing the HEPA/ULPA filter, turning on said
enclosures, testing for proper airflow, and then allowing workers back into the lab. Such a protocol
would be burdensome and difficult to delineate.
In comparison, two-stage ductless designs can be left on while the user changes out their
primary HEPA/ULPA filter. The secondary HEPA/ULPA filter provides constant protection as
they remove the used HEPA/ULPA filter, bag it inside the unit, and insert a new primary
HEPA/ULPA filter.
This design requires no lab evacuation, no enclosure shutdown, no airflow test, and no lab
personnel or patient disruption. Thus saving time, money, and minimizing the potential for
HD exposure. Furthermore, it is much more likely that proper filter change protocol will be
followed with two-stage ductless designs than in HEPA/ULPA externally vented enclosures.
Filter Alarms:
In addition, even if a user of a HEPA/ULPA filtered externally ventilated enclosure did follow the proper
protocol to change their filter (i.e. they evacuated the lab, re-entered the lab wearing a biohazard suit,
turned off all HEPA/ULPA filtered externally ventilated enclosures, changed the HEPA/ULPA filter, turned
on all said ventilated enclosures, tested for proper airflow, and then allowed workers back into the lab) -- how would they know when to change said filter?
The committee should understand that many total exhaust enclosures are not equipped with
HEPA/ULPA filter change alarms. In some cases, externally vented hoods may be equipped with manual
indicators in the form of additional mini or magna helic pressure gauges that display the pressure
differential across the HEPA/ULPA filter in the exhaust plenum. However, rarely do consumers fully
understand how to read and interpret these gauges. The proposed standard neither outlines a
procedure for such case, nor does the standard provide a means of testing user knowledge on reading
manual gauges as indicators of filter expiration.
At face value, HEPA/ULPA filter changes don’t seem that critical in externally vented enclosures.
However, if a HEPA/ULPA filter becomes clogged in an externally vented enclosure, then the blower
won’t be able to pull sufficient air through the unit. The user will lose negative pressure airflow.
Without proper air flow into the enclosure, containment is lost and the user will be exposed to HDs.
In comparison, single-stage and two-stage HEPA/ULPA filtered ductless enclosures are often
equipped with electronic filter change alarms. Electronic alarms remove the human factor
error associated with reading manual indicator gauges. These alarms constantly monitor the
HEPA/ULPA filter and audibly and visually alert the user when the filter is clogged. At this
point, the user may remove the HEPA/ULPA filter and replace it with a new one.
Unlike the HEPA/ULPA filtered externally vented enclosure, the user of a single-stage and twostage HEPA/ULPA filtered ductless enclosure immediately knows when their filter has become
clogged and is in need of replacement.
Airflow Issues:
When externally vented enclosures encounter airflow problems the user often does not know. The
reason is due to a lack of proper airflow monitors and blower controls. Often times increased sash
height, equipment location on the workbench, and even the number of enclosures pulling in the HVAC
system can lead to lowered, unsafe airflow levels in enclosures.
Simply put: why do chemistry labs stink? The externally ventilated enclosures aren’t maintaining proper
airflow. Were proper airflow maintained, air would never escape the front of an enclosure, and
technically speaking a lab space would smell no different than any other space in a building.
Though enclosures may be “inspected” once a year – sash height, equipment location within enclosure
space, and even personnel working at the face of the enclosure can change on a daily or even constant
basis. Each of these will affect airflow. Externally ventilated enclosures are not usually equipped with
variable speed blowers. Without said blowers, the enclosure cannot adjust speed to real-time enclosure
conditions. Why not? Most externally ventilated enclosures are designed for multiple enclosures to
hook into the HVAC ductwork.
However, the more enclosures that are connected to one blower, the lower the airflow will be in
enclosures furthest away from said blower. Externally ventilated enclosures try to combat this issue by
providing the user with vaneometers. These “controls” work off of a tissue-paper design -- if the paper,
or “indicator,” is being pulled in, airflow is heading into the unit. As you may assume, linking user safety
to the stagnancy and intelligence of a simple piece of material is not only flawed, but dangerously
negligent.
While airflow may be flowing into an enclosure, OSHA regulations state that a minimum of 60 linear feet
per minute should flow into the enclosure to maintain negative pressure. In an ever-changing lab
environment, only true, real-time variable-speed blowers ensure that proper airflow is maintained
within the enclosure space. However, since many externally ventilated enclosures work off of a multiple
unit to one-blower system, this is impossible since multiple variables change across each enclosure in
the lab.
In comparison, single-stage and two-stage filtration ductless enclosures work off of a oneenclosure one-blower system. With use of variable-speed blowers, the unit maintains proper
levels of airflow entering the workspace. In the unlikely event that airflow levels ever dip
below safe, pre-determined values (OSHA 19.10 states 60-120 linear feet per minute), proper
airflow monitors and controls will alert the user.
These safety precautions are absolutely necessary in providing the market with the highest
level of safety available. We would like to remind the committee that HEPA and ULPA filters
are built to a standard. These standards are 0.3 microns or larger with a 99.997% efficiency
for HEPA filters and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters. Given
that powdered HDs are caught by a HEPA filter (and certainly an ULPA filter), we believe users
have a right to use a ductless option in the lab with HDs and non-HDs.
Therefore, we would urge that both single-stage and two-stage HEPA filtered Class 1 BSC cabinets be
appropriate for use with HDs as already permitted according to lines 109, 227-228, & 281-282 as defined
in Appendix C (lines 1288-1298). Since ductless variations, that push contaminated air through a twostage HEPA/ULPA filtration process, are common, we believe that at the very least, these enclosures
should be accepted as C-PECs without the requirement of external exhaust.
Therefore we request that lines 271-272 be removed or amended to include the option of Class I BSC,
including single-stage or two-stage HEPA/ULPA filtered ductless enclosures.”
5.4 Nonsterile HD Compounding
5.4.1 C-PEC for Nonsterile HD Compounding
(Lines 281-282) “Nonsterile HD compounding shall be performed in a C-PEC that provides personnel and
environmental protection, such as a Class I BSC or CVE.”
(Lines 284-285) “The C-PEC used for nonsterile compounding shall be externally vented.”
Suggestion: We request that lines 284-285 “The C-PEC used for nonsterile compounding shall be
externally vented” be removed.
Explanation: When asepsis is not required, we agree with lines 109, 227-228, and 281-282 that a Class 1
BSC or CVE as defined in Appendix C: Types of Biological Safety Cabinets, lines 1288-1292 is appropriate.
Lines 1288-1292 in this proposed standard define a Class 1 BSC with the following statement: “Class 1: A
BSC that protects personnel and the environment but does not protect the product/preparation.
Personnel protection is provided as a minimum velocity of 75 linear feet/min of unfiltered room air is
drawn through the front opening and across the work surface. The air is then passed through a
HEPA/ULPA filter either into the room or to the outside in the exhaust plenum, providing
environmental protection.”
Per lines 109, 227-228 & 281-282, a Class 1 BSC which meets the appendix C definition of a Class 1 BSC is
appropriate for use with Hazardous Drugs. This means that air that passes through a HEPA/ULPA filter
back into the room is acceptable. However, the proposed standard states that in lines 284-285 the CPEC “shall be externally vented.” This contradicts previous lines (109, 227-228, 281-282) which allow a
Class 1 BSC and later lines (1288-1292) that define a Class 1 BSC.
By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns or larger with a
99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters.
Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders.
A Class 1 BSC is appropriate, financially feasible, and provides necessary safety for laboratory personnel
compounding with Hazardous Drugs. We request that lines 284-285 be removed.
Why Should a Ductless Class 1 BSC be appropriate for use with powdered HD Compounding?:
As previously stated in the comment section for lines 267-269 & 271-272; while we recognize and agree
with USP’s attempt to create a safer environment for pharmacists and technicians working with HDs, we
believe that the current standard creates unrealistic expectations for working environments. First and
foremost, it should be understood that an externally ventilated enclosure is not possible for a majority
of pharmacies that work with HDs. As previously stated, many small compounding businesses have
neither the space nor the means necessary for the renovations required to meet the proposed standard
in its current form.
Similar to the requirement for external venting of HD storage areas, external venting of all C-PEC’s may
not be attainable for all compounding pharmacies. For example, not all pharmacies own the building of
their business location. This may force pharmacies (outpatient clinics, long term care facilities, etc.) to
close unnecessarily due to a C-PEC requirement that cannot be physically met. Furthermore, this
regulation puts an unrealistic monetary requirement upon pharmacies dealing with HDs that may be
able to externally vent their C-PEC, but may not be able to bear the fiscal burden.
For example, in order to externally ventilate a 4’ enclosure at 100 lfpm for a typical workweek, the
pharmacy will be required to pay not only for the enclosure, but for its installation, ductwork, bends in
ductwork, blower requirements, make-up HVAC air, and utility costs for heating and cooling that makeup air. These costs are explained above, but can be estimated at approximately: $5,000 per enclosure,
$1,000 per 10’ of straight ductwork, $2,000 per required blower, $6,000-$12,000 for make-up airconditioning systems, and $5,000 - $7,000 per enclosure for heating and cooling costs associated with
make-up air. These estimates are per enclosure, and do not include bends in ductwork, nor electricity
costs associated with running the blower.
Please note, these costs should be multiplied for the number of enclosures the pharmacy requires.
While our company promotes the responsible handling and personal protection precautions for use with
HDs, we feel that the requirement of externally ventilating the C-PEC is unnecessary. If other C-PEC
solutions did not exist in today’s marketplace, we would gladly recommend and provide our customers
with externally ventilated enclosures. With recognition that we do manufacture (and will gladly provide
customers with) externally ventilated enclosures, we feel that this is excessive for the given application.
By design, HEPA/ULPA filters simply filter to a standard. These standards are 0.3 microns or larger with
a 99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters.
Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders.
Should the USP 800 committee feel that HEPA or ULPA filtration is not appropriate for capture of
powdered HDs, we ask that they provide the community with data to support this theory before
imposing cost-prohibitive standards upon the industry that will put many out of business.
Ductless enclosures with single-pass and dual-pass designs have been tested and certified by third
parties as appropriate for use with HDs, APIs, etc. In addition, HEPA/ULPA filtered ductless designs are
typically cheaper than the externally ventilated enclosure and only cost approximately $200 annually
in utilities, require no ductwork whatsoever, no installation whatsoever, and are found to be as safe
as, or safer, than HEPA-filtered externally vented enclosures, as shown below.
HEPA/ULPA filtered Ductless Enclosures vs. HEPA-filtered Externally Ventilated Enclosures
In order to provide the USP committee with thoughtful consideration of the safety of the HEPA-filtered
Externally Ventilated Enclosure design, we would like to compare this design to the HEPA/ULPA filtered
ductless design available on the market. We would like the committee to understand that AirClean
Systems is happy to provide the market with either design. We will gladly manufacture to the proposed
USP-800 standard. However, the committee should understand inherent flaws associated with
HEPA/ULPA-filtered Externally Ventilated Enclosures that single-stage and two-stage HELPA/ULPA
filtered ductless enclosures were designed to overcome.
Filter Changes:
To begin, the proposed USP 800 does not address filter changes on their HEPA/ULPA C-PEC design. How
will the user safely change filters when they have reached their maximum capacity? The committee
should understand that when a user goes to change the HEPA/ULPA filter in an externally vented
enclosure, they will typically need to turn the enclosure off (powering down the roof blower as well). At
this point, the user will lose all negative pressure within the enclosure and ductwork. Thus they risk
exposure to powders that remain in the enclosure, the inside of the exhaust plenum, ductwork, and
even on the HEPA/ULPA filter itself.
Given the exposure risk, the committee will need a protocol for this. Said protocol would need to:
evacuate the lab, outline appropriate biohazard suit procedures, enumerate procedures for powering
HEPA/ULPA filtered externally ventilated enclosures, changing the HEPA/ULPA filter, turning on said
enclosures, testing for proper airflow, and then allowing workers back into the lab. Such a protocol
would be burdensome and difficult to delineate.
In comparison, two-stage ductless designs can be left on while the user changes out their
primary HEPA/ULPA filter. The secondary HEPA/ULPA filter provides constant protection as
they remove the used HEPA/ULPA filter, bag it inside the unit, and insert a new primary
HEPA/ULPA filter.
This design requires no lab evacuation, no enclosure shutdown, no airflow test, and no lab
personnel or patient disruption. Thus saving time, money, and minimizing the potential for
HD exposure. Furthermore, it is much more likely that proper filter change protocol will be
followed with two-stage ductless designs than in HEPA/ULPA externally vented enclosures.
Filter Alarms:
In addition, even if a user of a HEPA/ULPA filtered externally ventilated enclosure did follow the proper
protocol to change their filter (i.e. they evacuated the lab, re-entered the lab wearing a biohazard suit,
turned off all HEPA/ULPA filtered externally ventilated enclosures, changed the HEPA/ULPA filter, turned
on all said ventilated enclosures, tested for proper airflow, and then allowed workers back into the lab) -- how would they know when to change said filter?
The committee should understand that many total exhaust enclosures are not equipped with
HEPA/ULPA filter change alarms. In some cases, externally vented hoods may be equipped with manual
indicators in the form of additional mini or magna helic pressure gauges that display the pressure
differential across the HEPA/ULPA filter in the exhaust plenum. However, rarely do consumers fully
understand how to read and interpret these gauges. The proposed standard neither outlines a
procedure for such case, nor does the standard provide a means of testing user knowledge on reading
manual gauges as indicators of filter expiration.
At face value, HEPA/ULPA filter changes don’t seem that critical in externally vented enclosures.
However, if a HEPA/ULPA filter becomes clogged in an externally vented enclosure, then the blower
won’t be able to pull sufficient air through the unit. The user will lose negative pressure airflow.
Without proper air flow into the enclosure, containment is lost and the user will be exposed to HDs.
In comparison, single-stage and two-stage HEPA/ULPA filtered ductless enclosures are often
equipped with electronic filter change alarms. Electronic alarms remove the human factor
error associated with reading manual indicator gauges. These alarms constantly monitor the
HEPA/ULPA filter and audibly and visually alert the user when the filter is clogged. At this
point, the user may remove the HEPA/ULPA filter and replace it with a new one.
Unlike the HEPA/ULPA filtered externally vented enclosure, the user of a single-stage and twostage HEPA/ULPA filtered ductless enclosure immediately knows when their filter has become
clogged and is in need of replacement.
Airflow Issues:
When externally vented enclosures encounter airflow problems the user often does not know. The
reason is due to a lack of proper airflow monitors and blower controls. Often times increased sash
height, equipment location on the workbench, and even the number of enclosures pulling in the HVAC
system can lead to lowered, unsafe airflow levels in enclosures.
Simply put: why do chemistry labs stink? The externally ventilated enclosures aren’t maintaining proper
airflow. Were proper airflow maintained, air would never escape the front of an enclosure, and
technically speaking a lab space would smell no different than any other space in a building.
Though enclosures may be “inspected” once a year – sash height, equipment location within enclosure
space, and even personnel working at the face of the enclosure can change on a daily or even constant
basis. Each of these will affect airflow. Externally ventilated enclosures are not usually equipped with
variable speed blowers. Without said blowers, the enclosure cannot adjust speed to real-time enclosure
conditions. Why not? Most externally ventilated enclosures are designed for multiple enclosures to
hook into the HVAC ductwork.
However, the more enclosures that are connected to one blower, the lower the airflow will be in
enclosures furthest away from said blower. Externally ventilated enclosures try to combat this issue by
providing the user with vaneometers. These “controls” work off of a tissue-paper design -- if the paper,
or “indicator,” is being pulled in, airflow is heading into the unit. As you may assume, linking user safety
to the stagnancy and intelligence of a simple piece of material is not only flawed, but dangerously
negligent.
While airflow may be flowing into an enclosure, OSHA regulations state that a minimum of 60 linear feet
per minute should flow into the enclosure to maintain negative pressure. In an ever-changing lab
environment, only true, real-time variable-speed blowers ensure that proper airflow is maintained
within the enclosure space. However, since many externally ventilated enclosures work off of a multiple
unit to one-blower system, this is impossible since multiple variables change across each enclosure in
the lab.
In comparison, single-stage and two-stage filtration ductless enclosures work off of a oneenclosure one-blower system. With use of variable-speed blowers, the unit maintains proper
levels of airflow entering the workspace. In the unlikely event that airflow levels ever dip
below safe, pre-determined values (OSHA 19.10 states 60-120 linear feet per minute), proper
airflow monitors and controls will alert the user.
These safety precautions are absolutely necessary in providing the market with the highest
level of safety available. We would like to remind the committee that HEPA and ULPA filters
are built to a standard. These standards are 0.3 microns or larger with a 99.997% efficiency
for HEPA filters and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters. Given
that powdered HDs are caught by a HEPA filter (and certainly an ULPA filter), we believe users
have a right to use a ductless option in the lab with HDs and non-HDs.
Therefore, we would urge that both single-stage and two-stage HEPA filtered Class 1 BSC cabinets be
appropriate for use with HDs as already permitted according to lines 109, 227-228, & 281-282 as defined
in Appendix C (lines 1288-1298). Since ductless variations, that push contaminated air through a twostage HEPA/ULPA filtration process, are common, we believe that at the very least, these enclosures
should be accepted as C-PECs without the requirement of external exhaust.
Therefore we request that lines 284-285 “The C-PEC used for nonsterile compounding shall be
externally vented” be removed.
(Lines 288-290) “A Class II BSC or a CACI may be used if it is dedicated for use with nonsterile
compounding or if it undergoes thorough cleaning and disinfection procedures after nonsterile
compounding and before re-use for sterile compounding.”
Suggestion: We suggest that the word “thorough” be further defined.
Explanation: While these lines contain an entirely reasonable expectation, the language used does not
designate the means of measuring what is a “thorough cleaning and disinfection” procedure. The
proposed USP-800 document should provide a definition for “thorough” or clear procedure for the
compounding supervisor (as outlined in lines 170-174) who will be responsible for enforcing lines 288290.
5.4.2 C-SEC for Nonsterile HD Compounding
(Lines 293-295) “The C-PEC shall be placed in a room that is physically separated (i.e., a different room
from other preparation areas) but does not need to be ISO 7 nor have HEPA-filtered air.”
(296-305) “The C-SEC shall meet the following requirements:
 Minimum of 12 ACHPH
 Maintained at a negative pressure of at least 0.01 inches of water column relative to all adjacent
spaces (rooms, above ceiling, and corridors). [NOTE-Although negative pressure within the HD
buffer area is important, the negative pressure should not be so strong that it induces
environmental contamination migration into the buffer area from unclassified adjacent spaces.]
 Due to the difficulty of cleaning HD contamination from surfaces, the architectural finish
requirements (e.g., smooth, seamless, impervious surfaces) prescribed in chapter (797) also
apply to nonsterile compounding areas (see Table 3).”
(306-307) “Table 3. Acceptable Configuration for Nonsterile HD Compounding
Function
C-PEC
C-SEC
Airflow
Maximum BUD
Nonsterile Compounding Any C-PEC C-SEC
12 ACPH (exhaust) As listed in (795)
See Appendix D for best practices for compounding nonsterile HDs.”
Suggestion: We request that lines 296-305 be removed, and that the airflow requirement for the C-SEC
in line 306 (“12 ACPH (exhaust)”) also be removed. We agree with the document’s wording on line 307
“any C-PEC” and do not wish to change the document.
Explanation: While we recognize and agree with USP’s attempt to create a safer environment for
pharmacists and technicians working with HDs, we feel that the current standard creates unrealistic
expectations for working environments. First and foremost, it should be understood that an externally
ventilated enclosure is not possible for a majority of pharmacies that work with HDs. As previously
stated, many small compounding businesses have neither the space nor the means necessary for the
renovations required to meet the proposed standard in its current form.
In regards to externally venting the C-SEC:
It may not be possible for certain businesses to meet the requirement in its current form for a number
of reasons. To begin, this requirement may be impossible to put into practice for many compounding
locations that don’t own the building of their business location. Those spaces may not allow them to
create structural changes to their location simply for a room in which HDs are handled.
Even if ownership of space exists, externally ventilating a room can cost approximately $1,000 per every
ten feet of ductwork required. This does not account for the cost of the blower on the roof (roughly
another $2,000 USD) nor does this cost include the utility cost to continuously run the blower (required
by the proposed standard- line 422).
It should be noted that this estimate per 10’ of ductwork is only for those labs that have straight line,
direct access to the external environment. For labs where ductwork needs to turn at a 90-degree angle,
additional charges will be incurred for each turn required of the ductwork to reach the roof from the
point of room ventilation.
In addition, this estimate does not take into account the additional ductwork (see costs above) and cost
of additional HVAC systems to create the make-up air necessary to meet the 12 ACPH required by the
proposed USP 800 standard. Typically one air-conditioning unit can range from $6,000-$12,000 USD.
Multiple HVAC make-up air-conditioning units might be required depending on room size. It should be
noted that this cost doesn’t include the energy charges associated with heating and cooling make-up air
before it is expelled to the external environment.
Because the standard requires that this system pull continuously, we must consider the increased
energy costs incurred to heat and cool this make-up air. Without knowledge of the size of each storage
room, a typical HVAC system pulling to give a 10’ x 10’ room at least 12 ACHPH, costs approximately
$5000 USD per year to run (costs will raise and lower slightly due to a change in kWh per location).
Again, these costs are estimates to meet the requirement on lines 297-302 that all HD storage areas
should be externally ventilated. These are not small costs as they require extensive remodeling.
These costs will generate anti-competitive market forces barring entry to smaller businesses and put
many existing companies out-of-business.
Finally, the committee should understand that in many cases, external venting is simply not feasible.
The most common reason for a lack of external vent access is due to building design itself. In many
cases, the facility cannot be retrofitted to allow for additional ductwork without compromising building
infrastructure. This is commonly the case in older buildings or buildings with multiple floors, affecting
many hospital pharmacies.
In other cases, the building HVAC alone has led to what is called “Sick Building Syndrome” (SBS) and
access has been closed off to labs. The term “Sick Building Syndrome” refers to situations in which
acute health issues have arisen as a result of time spent in a particular building. In laboratories and
compounding pharmacies, SBS arises as a result of an improper balance in lab ventilation and make-up
air. Typically, not enough air is pumped into the lab for the blower to pull the proper amount of air
through exhaust ductwork. As a result, containment is lost and occupants within the building suffer the
consequences.
Therefore, we request that lines 297-302 be removed, and that the “12 ACPH (exhaust)” requirement
in line 306 be removed.
In regards to architectural finish requirement (mentioned in lines 303-305):
How will seamless surfaces be obtained if shelves with raised lips are required per line 250? These
statements contradict one another.
Regardless of this contradiction, it may not be possible for certain businesses to meet the requirement
in its current form for a number of reasons. First, it effectively means that compounding practices will
be building Clean Rooms, as detailed in USP 797, simply to handle non-sterile compounds. This may be
impossible to put into practice for many compounding locations that don’t own the building of their
business location. In other cases, this requirement will be cost-prohibitive for many other pharmacies
and serve as an anti-competitive barrier to market entry.
Because this requirement seems to be excessive, cost-prohibitive, and impossible for many locations
to implement, we request that lines 303-305 be removed.
In regards to the acceptable C-PECs for Nonsterile Compounding:
Per lines 306-307, “Any C-PEC” is acceptable for use with non-sterile compounding. Line 109 defines
acceptable C-PECs for Nonsterile HD Compounding as: “Containment Ventilated Enclosure (CVE) or
Class I Biological Safety Cabinets (BSC).” This is mirrored in Lines 227-228 which define an acceptable
non-sterile HD Compounding C-PEC as “a Class I BSC, CVE, or an isolator intended for containment
applications may be sufficient.”
For the purposes of Nonsterile HD Compounding, when asepsis is not required, we agree that a CVE, an
isolator intended for containment applications, or a Class 1 BSC as defined in Appendix C: Types of
Biological Safety Cabinets, lines 1288-1292 is appropriate. We agree with the document’s wording in
this case.
Lines 1288-1292 in this proposed standard define a Class 1 BSC with the following statement: “Class 1: A
BSC that protects personnel and the environment but does not protect the product/preparation.
Personnel protection is provided as a minimum velocity of 75 linear feet/min of unfiltered room air is
drawn through the front opening and across the work surface. The air is then passed through a
HEPA/ULPA filter either into the room or to the outside in the exhaust plenum, providing
environmental protection.”
Per Lines 109, 227-228, a Class 1 BSC which meets the appendix C definition of a Class 1 BSC is
appropriate for use with Hazardous Drugs. This is affirmed in lines 306-307 with “any C-PEC” being
acceptable. This means that air that passes through a HEPA/ULPA filter back into the room is
acceptable. By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns or larger
with a 99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA
filters. Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD
powders. This option is appropriate, financially feasible, and provides necessary safety for laboratory
personnel compounding with Hazardous Drugs.
We agree with the document’s wording on line 307 “any C-PEC” and do not wish to change the
document.
However, if upon reading the Appendix C definition of a Class I BSC, the committee no longer feels that
this type of device is appropriate for use, then we request that the USP 800 provide the community
with data to support this theory before imposing cost-prohibitive standards upon the industry that will
put many out of business.
5.6 Nonsterile and Sterile Compounding
5.6.2 Engineering Control Operation
(Line 422) “The C-PEC shall operate continuously.”
Suggestion: We suggest removing line 422.
Explanation: As discussed, in order to externally ventilate a 4’ enclosure at 100 lfpm for a typical
workweek, the pharmacy will be required to pay not only for the enclosure, but for its installation,
ductwork, bends in ductwork, blower requirements, make-up HVAC air, and utility costs for heating
and cooling that make-up air. These costs are explained above, but can be estimated at approximately:
$5,000 per enclosure, $1,000 per 10’ of straight ductwork, $2,000 per required blower, $6,000-$12,000
for make-up air-conditioning systems, and $5,000 - $7,000 per enclosure for heating and cooling costs
associated with make-up air. These estimates are per enclosure, and do not include bends in ductwork,
nor electricity costs associated with running the blower.
Please note, these costs are estimated for a typical 40-hour workweek and should be multiplied for the
number of enclosures the pharmacy requires.
Should the proposed USP 800 standard require that these enclosures run continuously, the committee
should understand the heavy financial burden required to operate these enclosures. Pharmacies will
already need to pay $5000-$7000 per enclosure for heating and cooling costs associated with make-up
air. To require that the units run continuously (and be externally ventilated), will generate such
overhead costs as to put many market players out of business. Unless the committee’s aim is to distort
the free-market, these consequences should not be taken lightly.
In comparison, a single-stage or dual-stage HEPA/ULPA filtered ductless unit only costs approximately
$200 per year in utility costs. Considering that these units recirculate already heated and cooled lab air,
they allow businesses to operate with considerably lower, affordable costs. Should the USP 800
committee feel that the C-PEC unit need to run continuously, this solution should be included. This will
require the removal or editing of lines 263-266, 268-269, 271-272, & 284-285.
6. Personal Protective Equipment
6.1 Gloves
(Lines 475-479) “Wear two pairs of ASTM-tested chemotherapy gloves when compounding,
administering managing a spill, and disposing of HDs. For sterile preparations, the outer glove shall be
sterile. Wear the inner glove under the gown cuff and the outer glove over the cuff. Place gloves with
long cuffs over the cuff of the gown to protect the wrist and forearm.”
(Lines 488-491) “Change gloves every 30 min or when torn, punctured, or contaminated. Carefully
remove and discard them immediately in an approved HD waste container inside the C-PEC or contain
them in a sealable bag for discarding outside the C-PEC.”
Suggestion: We suggest removing lines 488-491.
Explanation: We understand that the USP committee is trying to implement a safe and reasonable
standard, but we must also evaluate the practicality of said standard. Is there any data to support the
reasoning behind changing of double ASTM-tested gloves every 30 min? We request the committee
provide data supporting this requirement. It would appear that requiring the changing of double ASTMtested gloves in an unnecessary situation (as with this frequency) would only lead to an increased risk of
exposure at the point in which gloves may be discarded outside of a C-PEC. Is there a way that the
facility can provide a validated process to allow for a longer glove use time?
6.5 Respiratory Protection
(Lines 552-554) “Personnel unpacking HDs that are not contained in plastic should wear an elastomeric
half-mask with a multi-gas cartridge and P100-filter. If the type of drug can be better defined, then a
more targeted cartridge could be used.”
Suggestion: We suggest that Class 1 BSC cabinets be accepted as an appropriate environment in which
HDs that are not contained in plastic can be unpacked without the requirement of an elastomeric halfmask with a multi-gas cartridge and P100-filter. We would like the following change to be included:
“Personnel unpacking HDs that are not contain in plastic should do so in a Class 1 BSC with appropriate
filtration or should wear an elastomeric half-mask with a multi-gas cartridge and P100-filter. If the type
of drug can be better defined, then a more targeted cartridge could be used.”
Explanation: It should be known that ductless Class I BSC cabinets exist for the unpacking of HDs and
bulk HDs that are not contained in plastic, but rather small, medium, or bulk containers. These cabinets
utilize specially blended carbon specific to the user’s compounding (during liquid handling) and single or
two-stage HEPA/ULPA filtration method for ensuring containment of HD powders.
These cabinets offer better airflow patterns overall and safer HEPA/ULPA and carbon filtration than the
elastomeric half-masks proposed. In addition, because carbon filters placed in these cabinets are
typically targeted for the user’s specific chemical, they provide a safer alternative to elastomeric halfmasks with general or multi-purpose filters.
While not all pharmacies have access (or possibly the space) for such a device, we would like to
propose that this type of device be included in lines (552-554) as appropriate measures of personal
protection while unpacking HDs and bulk HDs that are not contained in plastic.
9. Receiving
(Lines 644-648) “HDs should be received from the supplier sealed in impervious plastic to segregate
them from other drugs, to allow for safety in the receiving and internal transfer process, and should be
immediately delivered to the C-SEC. HDs shall only be stored in areas with the ventilation controls
described in this chapter.”
Suggestion: Lines 644-648 should be changed to read: “HDs should be received from the supplier in
sealed bulk drums, glass bottles, or impervious plastic to segregate them from other drugs to allow for
safety in the receiving and internal transfer process, and should be immediately delivered either to
proper storage or the C-SEC.” We suggest removing the statement: “HDs shall only be stored in areas
with the ventilation controls described in this chapter.”
Explanation:
Regarding Sealed Plastic Receiving Requirement:
Often, locations receive HDs in bulk drums, or glass bottles. These two means of packaging are
considered safe, and are not typically sealed in additional impervious plastic bags. Considering that the
proposed standard is trying to also serve as a functional document, we suggest that other safe means
(such as these) be included as acceptable means for receiving of HDs.
Regarding HD Receipt and Delivery:
The C-SEC as defined earlier in the chapter is not necessarily the same space as the HD externally vented
storage room. Lines (644-648) should note that delivery to either location is appropriate, should the
standard continue to require a separate externally ventilated storage room for HDs.
Regarding HD Storage Rooms:
Lines (647-648) state that “HDs shall only be stored in areas with the ventilation controls described in
this chapter.” According to the proposed standard, lines 237-240 require the storage room for HDs to
be externally ventilated.
As stated in the comments for lines 237-240: “It may not be possible for certain businesses to meet the
requirement in its current form for a number of reasons. To begin, this requirement may be impossible
to put into practice for many compounding locations that don’t own the building of their business
location. Those spaces may not allow structural changes to their location simply for drug storage, thus
potentially putting them out of business.
Even if ownership of space exists, externally ventilating a room can cost approximately $1,000 per every
ten feet of ductwork required. This does not account for the cost of the blower on the roof (roughly
another $2,000 USD) nor does this cost include the utility cost to continuously run the blower (required
by the proposed standard- line 422).
It should be noted that this estimate per 10’ of ductwork is only for those labs that have straight line,
direct access to the external environment. For labs where ductwork needs to turn at a 90-degree angle,
additional charges will be incurred for each turn required of the ductwork to reach the roof from the
point of room ventilation.
In addition, this estimate does not take into account the additional ductwork (see costs above) and cost
of additional HVAC systems to create the make-up air necessary to meet the 12 ACPH required by the
proposed USP 800 standard. Typically one air-conditioning unit can range from $6,000-$12,000 USD.
Multiple HVAC make-up air-conditioning units might be required depending on room size. It should be
noted that this cost doesn’t include the energy charges for heating and cooling make-up air before it is
expelled to the external environment.
Because the standard requires that this system pull continuously, we must consider the financial burden
to heat and cool this make-up air. Without knowledge of the size of each storage room, a typical HVAC
system pulling to give a 10’ x 10’ room at least 12 ACHPH, costs approximately $5000 USD per year to
run (of course costs will raise and lower slightly due to a change in kWh per location).
Again, these costs are estimates to meet the requirement on lines 237-240 that all HD storage areas
should be externally ventilated. These are not small costs as they require extensive remodeling.
These costs will generate anti-competitive market forces barring entry to smaller businesses and put
many existing companies out-of-business.
Finally, the committee should understand that in many cases, external venting is simply not feasible.
The most common reason for a lack of external vent access is due to building design itself. In many
cases, the facility cannot be retrofitted to allow for additional ductwork without compromising building
infrastructure. This is commonly the case in older buildings or buildings with multiple floors, affecting
many hospital pharmacies.
In other cases, the building HVAC alone has led to what is called “Sick Building Syndrome” (SBS) and
access has been closed off to labs. The term “Sick Building Syndrome” refers to situations in which
acute health issues have arisen as a result of time spent in a particular building. In laboratories and
compounding pharmacies, SBS arises as a result of an improper balance in lab ventilation and make-up
air. Typically, not enough air is pumped into the lab for the blower to pull the proper amount of air
through exhaust ductwork. As a result, containment is lost and occupants within the building suffer the
consequences.
If the committee feels strongly that storage of HDs is inappropriate in an area without ventilation, we
would like to suggest a safe, and cost-effective alternative solution. Ductless filtered cabinets are
common in the marketplace, and offer the user protection from HDs during storage.
Ductless filtered cabinets operate the same as Class I BSC enclosures by providing personnel and
environment protection. These cabinets achieve this by drawing in laboratory air to the cabinet space,
and then passing cabinet air through a HEPA (or ULPA) filter, before pushing filtered air back into the
room.
By design, HEPA/ULPA filters work to a standard. These standards are 0.3 microns or larger with a
99.997% efficiency for HEPA and 0.12 microns or larger with a 99.9995% efficiency for ULPA filters.
Thus, a HEPA filter (and certainly an ULPA filter) is more than adequate for the capture of HD powders
from within a cabinet space.
Ductless filtered cabinets recirculate room air and thus, cost only about $200 annually in utilities. These
cabinets require no installation, no ductwork, and no renovation to the laboratory space. They provide
pharmacies with the ability to grow in space, or change designs since the cabinet and filtration system
are typically one unit and can be moved.
In regards to safety, ductless filtered storage cabinets can avoid the pitfalls of HVAC systems (i.e. Sick
Building Syndrome), by providing real-time filter monitoring, airflow monitoring, with audible and visual
alarms to alert the user in the event of unsafe conditions. Without the same burdens and potential
pitfalls associated with whole-room ventilation, ductless filtered storage cabinets are more readily
adopted and implemented in the workplace.
Finally, ductless filtered storage cabinets are more easily containment tested and challenge tested to
ensure proper safety conditions are being met. By performing third-party containment tests the user
can be assured that HDs are being confined to the interior space of the cabinet. By performing thirdparty particle-count challenge tests on post-filtered air, the user can be assured that HDs are being
properly caught by the HEPA/ULPA filter.
Ductless filtered storage cabinets are a realistic, feasible, cost-effective, testable, and safe alternative to
externally vented storage rooms.
Therefore, we request that the statement in lines 239-240 be removed: “which includes storage in a
negative pressure room with at least 12 air changes per hour (ACPH).”
12. Compounding HD Dosage Forms
(Lines 750-781) “Compounding personnel are responsible for ensuring that HDs are accurately
identified, measured, diluted, and mixed and are appropriately sterilized (when appropriate), packaged,
sealed, labeled, stored, dispensed, and distributed. These performance responsibilities include
maintaining clean conditions and providing labeling and supplementary instructions for the proper
administration of HDs.
Work practices for compounding nonsterile HD dosage forms shall include:
 Using requirements listed in chapter (795)
 Avoiding use of active pharmaceutical ingredients (APIs) if a suitable manufactured product is
available and appropriate for use, e.g., using an injection rather than a bulk powder
 Manipulation of any HDs (such as crushing tablets or opening capsules) shall be performed
carefully, within a C-PEC using appropriate PPE. Clean equipment (such as mortars and pestles,
spatulas, and others) shall be dedicated for use with HDs. Crushing tablets or opening caps
should be avoided if possible; liquid formulations should be used if oral solids are not
appropriate for the patient.
 Handling bulk containers of liquid HDs carefully to avoid spills. These containers shall be
dispensed and maintained in sealable, impervious plastic bags or other suitable containers to
contain any inadvertent contamination.
 Ensuring that processes for labeling the compound do not introduce contamination into non-HD
areas.
 Dispensing in the final dose and form whenever possible.
Work practices for compounding sterile HD dosage forms shall include:
 Using requirements listed in chapter (797).
 Avoiding the use of APIs if a suitable manufactured product is available and appropriate for use,
e.g., using an injection rather than a bulk powder.
Appropriately preparing materials used in compounding before introduction into the Class II BSC or the
pa-through of a CACI (see chapter (797) for details).
 Ensuring that processes for labeling the compound do not introduce contamination into non-HD
areas.
The compounding areas shall be properly cleaned after compounding activities.”
Suggestion: We suggest removing Lines 757-759, 764-765, and 774-774.
Explanation: We would like to submit to the committee our thoughts on this section of USP 800 for
further review. Lines 757-759, 764-765, and 774-774 put an unnecessary restriction on the
compounding pharmacist in regards to the use of APIs to force them to use manufactured, and liquid
formulations.
19. Medical Surveillance
(Lines 970-973) “The goal of medical surveillance is to minimize adverse health effects in workers
exposed to HDs. A medical surveillance program involves collecting and interpreting data to detect
changes in the health status of working populations potentially exposed to hazardous substances.”
(Lines 977-978) “Employers shall ensure that healthcare workers who are exposed to HDs are routinely
monitored as part of a medical surveillance program.”
Suggestion: We suggest removing lines 970 -973 and lines 977-978.
Explanation: The standard doesn’t give clear instruction as to what the required medical surveillance
practice is, nor what it should appear to be.
While this comment is an entirely reasonable expectation, the language used is vague and does not
specify what “data” needs to be collected, or interpreted. Does the worker have the right to opt out of
such a program due to privacy concerns? If so, how does the proposed standard apply in this case?
The laws, regulations, and standards to which compounders and compounding owners are held should
be clearly defined. The proposed standard states a requirement but gives no direction on
implementation or how to achieve compliance. Unfortunately, that seems to be an all-too frequent
case in this industry.