Dated: January 7, 2008
Jason B. Elster
BEFORE THE ILLINOIS POLLUTION CONTROL BOARDR
Ec EivED
CLERK'S OFFICE
BIOMEDICAL TECHNOLOGY SOLUTIONS, )
INC., a Colorado Corporation,
JAN 0 7 2008
STATE
OF ILLINOIS
Petitioner, )
Pollution Control Board
v.
) AS 08-6
) (Adjusted
Standard - PIMW)
ILLINOIS ENVIRONMENTAL PROTECTION )
AGENCY,
)
Respondent. )
NOTICE OF FILING
To: Illinois
Environmental Protection Agency
Division of Legal Counsel
c/o Kyle Davis, Esq.
1021 North Grand Avenue East
P.O. Box 19276
Springfield, Illinois 62794-9276
PLEASE TAKE NOTICE that I filed with the Office
of the
Clerk
of the Pollution
Control Board the foregoing Motion to File
Instanter
Amended Petition for Adjusted
Standard of BioMedical Technology Solutions, Inc., a copy of which is herewith served
upon you.
Neal H. Weinfield
Jason B. Elster
GREENBERG TRAURIG, LLP
Firm No. 36511
77 West Wacker Drive, Suite 2500
Chicago, Illinois 60601
312-456-8400 (Telephone)
312-456-8435 (Facsimile)
weinfieldn@gtlaw.com
elsterj@gtlaw.com
BEFORE THE ILLINOIS POLLUTION CONTROL BOARD
BIOMEDICAL TECHNOLOGY SOLUTIONS,
INC., a Colorado Corporation,
Petitioner,
RECEIVED
CLERK'S OFFICE
JAN 0 7 20:3
STATE OF ILLINOIS
Pollution Control Board
v.
?
AS 08-6
(Adjusted Standard - PIMW)
ILLINOIS ENVIRONMENTAL PROTECTION
AGENCY,
Respondent.
CERTIFICATE OF SERVICE
I, Jason B. Elster, an attorney, certify that I have caused a true and correct copy of
the foregoing MOTION TO FILE
INSTANTER
AMENDED PETITION FOR
ADJUSTED STANDARD and NOTICE OF FILING to be served before 5:00 p.m. via
First Class Express Mail, overnight delivery, postage pre-paid, on the following:
Illinois Environmental Protection Agency
Division of Legal Counsel
do Kyle Davis, Esq.
1021 North Grand Avenue East
P.O. Box 19276
Springfield, Illinois 62794-9276
Dated: January 7, 2008
Jason B. Elster
BEFORE THE ILLINOIS POLLUTION CONTROL BOARD
Rec
CLERK'S
EIVE
OFFICE
D
JAN 0
7 2C38
STATE OF ILLINOIS
Pollution Control Board
AS 08-6
(Adjusted Standard -
PIMW)
ILLINOIS ENVIRONMENTAL PROTECTION
AGENCY,
Respondent.
MOTION TO FILE
INSTANTER
AMENDED PETITION FOR ADJUSTED STANDARD
Petitioner BioMedical Technology Solutions, Inc. ("BMTS"), by and through its
undersigned attorneys, hereby files
instanter
its Amended Petition for Adjusted Standard
pursuant to the Illinois Pollution Control Board's (the "Board") order of December 20,
2007 (the "Order"), and states as follows:
1.
On November 28, 2007, BMTS filed a petition for a statewide adjusted
standard of 35 Ill. Adm. Code 1422.Appendix A, Table B (the "Petition"). Shortly
thereafter, BMTS filed the proof of timely publication of notice of the Petition's filing, as
well as certificates of publication stating that notice was published in both the
Chicago
Tribune
and the
State Journal Register
on December 6, 2007.
See
Order at 1.
2.
On December 20, 2007, the Board entered the Order accepting the Petition
and "finding that it meets the content requirements of Section 104.406 of the
[Environmental Protection] Act." Order at 1.
3.
Because of a discrepancy in preferred nomenclature, the Board directed
BMTS to clarify which designation of the same indicator microorganism,
Bacillus
atrophaeus
(ATCC 9372) or
Bacillus subtilis
var
niger
(ATCC 9372), that BMTS is
BIOMEDICAL TECHNOLOGY SOLUTIONS,
INC., a Colorado Corporation,
Petitioner,
v.
requesting be substituted in 35
Ill.
Adm. Code 1422.Appendix A, Table B by filing an
amended petition on or before January 7, 2008.
See
Order at 2.
4.
While both designations refer to the same microorganism, the designation
Bacillus atrophaeus
(ATCC 9372) is preferable to
Bacillus subtilis
var
niger
(ATCC
9372).
5.
Therefore, pursuant to the Board's Order, BMTS respectfully submits the
following substantive amendment to its Petition for Adjusted Standard:
IX.
?
Narrative Description of the Proposed Adjusted Standard
35 IAC 104.406(1) requires that the Petition provide a narrative
description of the proposed adjusted standard as well as proposed
language for a Board order that would impose the standard. The Adjusted
Standard would simply involve formally recognizing the appropriateness
of both the Certified and Chemical Indicators in Table B of 35 IAC 1422
for the validation of dry heat and chemical sterilization processes,
respectively. The proposed language for a Board order would involve
amending Item 1 of Table B from
"I.
Bacillus subtilis (ATCC 19659)" to
"1. Bacillus subtilis (ATCC 19659) or Bacillus atrophaeus (ATCC
9372)". This language recognizes the recent change in classification of
this particular isolate of Bacillus subtilis.
35 IAC 104.406(0 further requires the Petition to describe efforts
necessary to achieve this proposed standard and the corresponding costs
must also be presented. BMTS has already completed an Initial Efficacy
Test demonstrating a 6 log i
n reduction of
B. atrophaeus
(ATCC 9372)
under varying load conditions. Thus, no additional efforts are required by
the Petitioner if the proposed standard is adopted.
Amended Petition for Adjusted Standard, attached hereto as
Exhibit 1.I
WHEREFORE, Petitioner BioMedical Technology Solutions, Inc. hereby files
instanter
its Amended Petition for Adjusted Standard and respectfully requests that this
Board, pursuant to its authority under Section 35 of the Act and the Board's regulations
Per the Board's Order, the Amended Petition clarifies that BMTS is requesting that Bacillus
atrophaeus
(ATCC 9372) be substituted into 35 III. Adm. Code 1422.Appendix A, Table B. Aside from revisions to
Dated: January 7, 2008
By:
One of Its Attorneys
under 35 IAC 104, grant BMTS an Adjusted Standard from the provisions of 35 IAC
1422.Table B recognizing
Bacillus atrophaeus
(ATCC 9372) as the most appropriate
biological indicator organism for the validation of dry heat sterilization technologies, and
grant BMTS any other relief the Board deems just.
Respectfully Submitted,
BIOMEDICAL TECHNOLOGY
SOLUTIONS, INC.
Neal H. Weinfield
Jason B. Elster
GREENBERG TRAURIG, LLP
Firm No. 36511
77 West Wacker Drive, Suite 2500
Chicago, Illinois 60601
312-456-8400 (Telephone)
312-456-8435 (Facsimile)
weinfieldn@gtlaw.com
elsterj@gtlaw.com
ensure consistency, the above-excerpted language is the only substantive change to the Petition.
References to any exhibits in the Amended Petition are identical to those submitted with the Petition.
Exhibit 1
EXHIBIT 1
BEFORE THE ILLINOIS POLLUTION CONTROL BOARD
BIOMEDICAL TECHNOLOGY SOLUTIONS,
INC., a Colorado Corporation,
Petitioner,
v.
?
AS 08-6
(Adjusted Standard -
PIMW)
ILLINOIS ENVIRONMENTAL PROTECTION
AGENCY,
Respondent.
AMENDED PETITION FOR ADJUSTED STANDARD
Petitioner BioMedical Technology Solutions, Inc. ("BMTS"), by and through its
undersigned attorneys, hereby petitions the Illinois Pollution Control Board (the "Board")
for an Adjusted Standard from a provision of 35 IAC 1422. BMTS, which manufactures
a countertop medical waste treatment device, the Demolizer® technology, seeks a
technology-specific Adjusted Standard from 35 IAC 1422, which requires the use of a
particular microorganism,
Bacillus subtilis
(ATCC 19659), to determine the initial
efficacy of the technology. In conducting the initial efficacy test required under the
Board's regulations, BMTS seeks permission to use a subspecies of
Bacillus subtilis
commonly referred to as
Bacillus atrophaeus
(recently reclassified from
Bacillus subtilis
var.
niger)
that is the preferred and most appropriate biological indicator organism for the
validation of dry heat sterilization processes. The proposed Adjusted Standard exhibits
superior dry heat resistance and can be distinguished from the generic
Bacillus subtilis
primarily through differences in color or pigmentation response to certain media.
Importantly, the proposed Adjusted Standard is nationally and internationally recognized
by microbiologists and governing standards organizations as the preferred and most
appropriate biological indicator organism for the validation of dry heat sterilization
technologies, the underlying technology of the Demolizer® system. Further, it is the
only
Bacillus subtilis
organism available in a tested, certified carrier form. This petition
for an Adjusted Standard (the "Petition") is brought pursuant to Section
35
of the Illinois
Environmental Protection Act (the "Act"),
415 ILL. COMP. STAT. 5/35,
and Part
104
of
Chapter
35
of the Illinois Administrative Code,
35
IAC
104.
In support of its Petition,
BMTS states as follows:
I.
?
Introduction
BMTS manufactures medical waste treatment devices that, employing
Demolizer® technology, destroy potentially infectious microorganisms through the use
of dry-heat. Prior to conducting a treatment cycle, medical wastes, including "sharps,"
are placed into the device, which is approximately the size of the common microwave.
Through the course of a treatment cycle, the waste is sterilized and rendered into a non-
recognizable solid waste that can then be disposed of as any other refuse. Businesses that
generate relatively low volumes of medical waste such as nursing homes, medical, dental
and veterinary offices, and pharmacies can use BMTS devices on-site as a safe and
efficient method of treating and disposing these materials. It also avoids having to ship
medical waste off-site for treatment and disposal. In fact, BMTS devices can be found
throughout the United States and BMTS has begun marketing the technology world-wide.
The technology is formally approved or meets statutory requirements in
46
states.
In order to sell its devices in Illinois, the Board's regulations require that BMTS
demonstrate that its Demolizer® technology is effective in eliminating potentially
harmful microorganisms by performing an Initial Efficacy Test ("JET"). The purpose
of
2
an IET is to validate the sterilization efficacy of a treatment device. Currently, the
Board's regulations specify that a particular microorganism, ATCC 19659
Bacillus
subtilis
("Chemical Indicator"), must be used in the IET. However, ATCC 19659
1 is not
commercially available in a certified form, and the procedure for growing and certifying
ATCC 19659 to the same standards achieved using the most appropriate
Bacillus subtilis
certified microorganism could take close to two and a half years and cost upwards of
$320,000 - which would require that BMTS sell numerous additional Demolizer® units
just to cover these costs. [Exhibit J]
The alternative to ATCC 19659 is a variant of the same species, ATCC 9372
Bacillus atrophaeus,
also known as
Bacillus subtilis
var.
niger
("Certified Indicator" or
"Dry Heat Indicator"), which is commercially available in a certified form and is the
scientifically-recognized standard in 46 states as well as the international community for
the validation of dry heat sterilization processes due to its superior growth and heat
resistance properties.
The Certified and Chemical Indicator organisms are very similar organisms. The
Chemical Indicator,
Bacillus subtilis,
is commonly used for the validation of chemical
disinfectants and is, therefore, most appropriate for the validation of alternative
technologies employing a chemical sterilization agent. The Chemical Indicator is not
recognized by international standards organizations or in the scientific literature for the
validation of dry heat sterilization technologies.
The American Type Culture Collection, commonly known as the ATCC, is an international nonprofit
organization that provides biological products and technical services to the scientific community. The
biological samples deposited with the ATCC are used internationally as the reference standard for
biological materials.
See
ATCC, http://www.atcc.org/About/AboutATCC.cfm (last visited June 20, 2007).
3
The Certified Indicator,
Bacillus subtilis
var.
niger
(reclassified as
Bacillus
atrophaeus
in 2004), exhibits enhanced resistance in dry heat applications compared to a
generic
Bacillus subtilis
organism, typical of the Chemical Indicator. In a definitive
study conducted by Gurney and Quesnel, the dry heat resistance performance of a generic
Bacillus subtilis
and
Bacillus subtilis
var.
niger
were compared at dry heat treatment
temperatures ranging form 140 to 170°C. At all temperatures,
Bacillus subtilis
var
niger
demonstrated superior dry heat resistance. The study definitively found that "the var.
niger
strain is clearly the organism of choice as an indicator of dry heat sterilization..."
See
Group Exhibit H, Gurney, T.R. & Quesnel, L.B.,
Thermal Activation and Dry-heat
Inactivation of Spores of Bacilus subtilis MD2 and Bacillus subtilis var. niger, J.
APPLIED BACTERIOLOGY, 48, 231-247 (1980).
Based on these findings and the preponderance of evidence in the scientific
community, the Certified Indicator has been universally adopted as the preferred and
most appropriate biological indicator organism for the validation of dry heat sterilization.
The following international standards organizations specify the proposed Adjusted
Standard,
Bacillus subtilis
var.
niger
(ATCC 9372) as the preferred biological indicator
organism for dry-heat processes. Each standards organization convenes an expert panel
of microbiologists and specialists in sterilization assurance that review the body of
scientific evidence to substantiate their recommendations and published standards.
Manufacturers of certified biological indicators must then test each production lot against
these standards meeting stringent performance requirements for resistance as measured in
D-values and z-values.2
2
The D-value is the time required to destroy 90% (I logIO reduction) of cells under specified conditions
while the z-value is the increase in temperature required to reduce the thermal death time by a factor of 10.
4
1.
US
Pharmacopoeia.
USP28-NF23 USP. Monographs: Biological Indicator
for Dry-Heat Sterilization, Paper Carrier; Rockville, MD; 2005.
2.
FDA.
Guidance on Premarket Notification [510(k)] Submissions for
Sterilizers Intended for Use in Health Care Facilities. Infection Control
Devices Branch, Division of General and Restorative Devices (March 1993).
3.
FDA. Premarket Notifications [510(k)] for Biological Indicators Intended to
Monitor Sterilizers Used in Health Care Facilities; Draft Guidance for
Industry and FDA Reviewers; U.S. Department of Health and Human
Services, Food and Drug Administration, Center for Devices and Radiological
Health, Infection Control Devices Branch (March 2001).
4.
British Pharmacopoeia Commission.
Methods of sterilization. London,
UK: British Pharmacopoeia Commission; British Pharmacopoeia Appendix
XVIII (2003).
5.
European Pharmacopoeia Commission.
Biological indicators of
sterilization. Strasbourg, France: European Pharmacopoeia Commission;
European Pharmacopoeia EP 5.1.2 (1997).
6. Japanese Pharmacopoeia.
JP14e.part1I.15 JP. Terminal Sterilization and
Sterilization Indicators.
7.
ISO and ANSI.
Sterilization of health care products – Biological indicators;
Part 4: Biological indicators for dry heat processes. Geneva (Switzerland):
International Organization for Standardization/ANSI; ISO 11138-4:2006.
BMTS is requesting relief from the Board's requirement of using the Chemical
Indicator in the IET and seeks permission to demonstrate the effectiveness of its devices
by conducting the IET using the Certified Indicator. Currently, out of the 46 states that
have approved the Demolizer® or for which the Demolizer® meets statutory
requirements, Illinois is the only state that has required use of the Chemical Indicator in
the IET for the Demolizer® technology rather than the Certified or Dry Heat Indicator for
the validation of the dry heat sterilization technology.
5
II. Regulatory
Requirements For Conducting An Initial Efficacy Test
35 IAC 104.406(a) requires that the Petition contain a statement describing the
regulation from which an Adjusted Standard is sought. Pursuant to 35 IAC 1422.124,
"[t]he manufacturer, owner or operator of a treatment unit shall conduct an Initial
Efficacy Test, pursuant to Appendix A of this Part, for each model prior to its operation."
35 IAC 1422.124(a). The IET is a scientifically-controlled demonstration that the
treatment unit does in fact eliminate the infectious potential from potentially infectious
medical waste. Section 1422.Appendix A ("Appendix A"), titled Initial Efficacy Test
Procedures, sets forth the procedures for conducting an IET for three classes of treatment
units.
See
35 IAC 1422.Appendix A.
The IET procedure that applies to BMTS involves placing carriers of indicator
microorganisms inside the device, conducting a treatment cycle, and then measuring the
number of indicator microorganisms that remain viable.
See id.
Appendix A identifies
three indicator microorganisms to be used in an IET for treatment units that use thermal
treatment and maintain the integrity of the container of indicator microorganisms (e.g.,
incinerators, autoclaves, and radiation-based processes): 1)
Bacillus subtilis
(ATCC
19659); 2)
Bacillus stearothermophilus
(ATCC 7953); and 3)
Bacillus pumilus
(ATCC
27142).
See
35 IAC 1422.Table B ("Table B"). The Agency has agreed that the second
and third indicator microorganisms are not scientifically appropriate for verifying the
efficacy of the Demolizer® system because they are not recognized for the validation of
dry heat systems. The effective date of the regulation is March 1993.
6
III.
Statement of Applicability
As required by 35 IAC 104.406(b), the regulation of general applicability was not
promulgated to implement, in whole or in part, the requirements of the CWA (33 USC
1251 et seq.), Safe Drinking Water Act (42 USC 7401 et seq.), or the State programs
concerning RCRA, UIC, or NPDES [415 ILCS 5/28.1].
IV.
Level of Justification
35 IAC 104.406(c) requires the Petitioner to state whether a specific level of
justification is provided in the regulation of general applicability. 35 IAC 1422 does not
specify a level of justification or other requirements.
V.
Description of the Nature of the Petitioner's Activity
35 IAC 104.406(d) requires a complete and concise description of the nature of
BMTS' activity that is the subject of the proposed Adjusted Standard. BMTS was
incorporated in 2005 as a Colorado corporation. BMTS produces medical waste
treatment devices that employ Demolizer® technology, which is based on a dry-heat
treatment process that was developed and broadly approved throughout the United States
in the mid-1990s. The technology heats one gallon of medical waste to a minimum
treatment temperature of 350°F for a minimum of 90 minutes. The Demolizer®
technology has demonstrated broad-scale efficacy under these treatment conditions
through studies at Stanford University, Kansas State University, and various private
laboratories. BMTS has customers in almost every state and has begun marketing the
technology world-wide. Further, the temperature profile completely destroys sharps
waste through a slow-melting of the plastic components of used syringes. The resulting
7
melted mass is further contained in the bottom of the metal collector for final disposal as
ordinary solid waste.
A.
BMTS' Initial Efficacy Test Using the Certified Indicator
In 2006, BMTS commissioned Dr. James Marsden, Regent's Distinguished
Professor at Kansas State University, to conduct an initial efficacy test for its updated
Demolizer® technology that could be used to secure regulatory approval both in the
United States and internationally (the "KSU Efficacy Test"). In selecting an appropriate
indicator microorganism, Dr. Marsden conducted a comprehensive review of the
scientific literature prior to initiating the efficacy trial.
In his preparations for the KSU Efficacy Test, Dr. Marsden discovered that the
Chemical Indicator was not commercially available in a certified spore carrier form.
However, the scientifically similar Certified Indicator, which is the industry standard for
validating dry-heat sterilization technologies due to superior heat resistance, was readily
available from multiple certified manufacturers including STERIS Corporation, NAMSA,
Raven Laboratories, STS, and Charles River Laboratories, to name a few. Through his
literature review, Dr. Marsden concluded that the Chemical and Certified Indicators are
essentially equivalent with primary differentiation based on pigmentation response to
certain media. In fact, over 99.8% of their genetic material is
identical -
meaning that,
but for their color, the Chemical and Certified Indicators are indistinguishable.3
Most importantly, Dr. Marsden determined that the international scientific
community, including many of the world's most prestigious standards organizations,
recognizes the Certified Indicator as the preferred and most appropriate biological
3
See
Group Exhibit H,
infra,
K.S. Blackwood, C.Y. Tureene, D. Harmsen, and A.M. Kabini„
Reassessment of Sequence-Based Targets for the Identification Bacillus Species, J.
CLINICAL
MICROBIOLOGY,
42, No. 2 (2004).
8
indicator for the validation of dry heat processes. As cited in the previously,
Bacillus
subtilis
var.
niger,
the Certified Indicator, exhibits enhanced resistance in dry heat
applications compared to a generic
Bacillus subtilis
organism, typical of the Chemical
Indicator.
Therefore, it was the recommendation of Dr. Marsden, consistent with the
overwhelming body of scientific literature, to use the commercially available Certified
Indicator in the KSU Efficacy Test. This approach poses the most rigorous challenge for
the Demolizer® technology and relies on the use of tested and standardized indicator
spore carriers.
The results from the KSU Efficacy Test conclusively established that the
Demolizer® technology is an effective sterilization treatment for potential infectious
medical waste. Since complete elimination or destruction of all forms of microbial life is
difficult to prove, sterilization is usually expressed as a probability function in terms of
the number of microorganisms surviving a particular treatment process. Under the
Board's regulations, a valid sterilization process must demonstrate a one-millionth
survival probability in the indicator microorganism population.4
The Demolizer®
devices used in the KSU Efficacy Test unequivocally demonstrated their ability to meet
Illinois' requirements for sterilization devices.
B.?
Historical Classification and Subsequent Sub-Classification of the
Bacillus Subtilis
Species
The following provides a discussion of the subspecies reclassification of the
Bacillus
genus that affects
Bacillus subtilis
organisms.
The Board's regulations express this probability function is a 6 Log
i°
reduction,
i.e
a 99.9999%
reduction in microbial life.
9
Until 1989, the scientific community recognized the Chemical and Certified
Indicators as members of the
Bacillus
family commonly referred to as
Bacillus subtilis.
Migula first described the species now know as
Bacillus subtilis
in 1900.
See
Migula,
W.,
System der Bakterien,
vol. 2.
JENA: GUSTAV FISCHER
(1990). In 1952, Smith
et al.
noted that certain strains of
Bacillus subtilis
produced different colored pigments when
exposed to varying culture conditions, but otherwise found no other discriminatory
property between the strains other than pigmentation.
See
Smith, N.R., Gordon, R. E. &
Clark, F.E.,
Aerobic Spore-forming Bacteria,
AGRICULTURE MONOGRAPH
No. 16,
Washington, DC: United States Department of Agriculture (1952). In that same work,
Smith
et al.
allocated certain strains into a subspecies variety called
Bacillus subtilis
var.
niger. See id.
However, in 1973, these different varieties were once again subsumed into the
broader species designation
Bacillus subtilis
through the work of Gordon
et al.
due to the
lack of differentiation between varieties.
See
Gordon, RE., Haynes, W.C. & Pang, C.
H.-N.,
The Genus Bacillus,
AGRICULTURE HANDBOOK
No. 427, Washington, DC: United
States Department of Agriculture (1973). In 1989, Nakamura re-examined the pigment-
producing strains of
Bacillus subtilis
and, just like Smith
et al.,
once again differentiated
certain subspecies based on pigmentation.
See
Group Exhibit H,
infra,
Nakamura, L.K.,
Taxonomic Relationship of Black-Pigmented
Bacillus Subtilis
Strains and a Proposal for
Bacillus Atrophaeus
sp. nov.,
INT. J. SYST. BACTERIOLOGY
39, 295-300 (1989).
This time, Nakamura created a new subspecies designation,
Bacillus atrophaeus,
which included 21 of the 25 strains that had previously been designated as
Bacillus
subtilis
var.
niger. See id.
Henceforth, the Certified Indicator belonged to the
subspecies
10
atrophaeus
while the Chemical Indicator remained part of the subspecies
subtilis.
In
making this distinction between strains, Nakamura noted that the species descriptions of
Bacillus subtilis
and
Bacillus atrophaeus
are not affected by the re-classification because,
"except for the colour of the soluble pigment, all of the strains were indistinguishable by
the standard characterization method;
i.e.
they exhibited the traits typical of
B. subtilis."
Id.; see also
Fritze, D. and Pukall, R.,
Reclassification of Bioindicator Strains
Bacillus
Subtilis
DSM 675 and
Bacillus Subtilis
DSM 2277 as
Bacillus Atrophaeus,
INT'L.
J.
SYSTEMATIC EVOLUTIONARY MICROBIOLOGY,
51, 35-37 (2001).
Since Nakamura's 1989 re-classification of
Bacillus subtilis
strains, the scientific
community has consistently and unanimously found that members of the
Bacillus subtilis
and
Bacillus atrophaeus
are phenotypically identical except for color.
See generally,
Group Exhibit H,
infra.
C.?
BMTS' Regulatory Approval Efforts
As part of the KSU Efficacy Test, extensive trials were conducted on the updated
Demolizer® technology utilizing an array of organisms under varying conditions as
required by the Illinois statutes and other state agencies across the United States. These
results have been exhaustively reviewed by many of the states that formally approve such
technologies and resulted in the issuance of technology approval letters. Only three states
specifically identify the Chemical Indicator in their regulations for use in validation
procedures: Arizona, Illinois, and Delaware. In fact, both Arizona and Delaware have
reviewed the KSU Efficacy Test that used the Certified Indicator and issued approval for
the technology based on its findings. To date, BMTS' Demolizer® technology is either
approved or meets statutory requirements in 46 states. Historically, the technology has
11
been reviewed favorably by over 75 federal, state, and local agencies, and it meets
statutory requirements for treatment across the United States and throughout the
international community. Exhibit I contains regulatory approval documentation from
select states, including the States of Arizona and Delaware, which have accepted the
Certified Indicator as equivalent to the Chemical Indicator. This information has been
previously provided to the Illinois Bureau of Land in September 2007 in support of the
Agency's review of this petition.
In mid-October 2006, BMTS contacted the Illinois Environmental Protection
Agency (the "Agency") to request that the Agency consider a continuous monitoring
system as an alternative to biological testing consistent with the provisions of 35 IAC
1422.125(a)(3).
5 After speaking with an Agency representative, BMTS submitted a
formal request that included the KSU Efficacy Test results on October 19, 2006. Over
the next few months, BMTS periodically contacted the Agency to check on the status of
its request and was told that a response would be issuing shortly. In January 2007,
BMTS received a formal response from the Agency stating that, in the Agency's opinion,
the KSU Efficacy Test did not conform with the IET requirements. A true and correct
copy of the Agency's January 5, 2007 Letter is attached hereto as Exhibit A.
After receiving the Agency's January 5, 2007 letter, BMTS agreed to provide the
Agency with additional information to resolve the issue regarding the IET, which was
transmitted on January 10, 2007. A true and correct copy of BMTS' January 10, 2007
Correspondence is attached hereto as Exhibit B. Over the next four months, BMTS
periodically contacted the Agency to inquire as to its review of the additional information
5
Formal approval from the Agency is required in order for a manufacture like BMTS to use a continuous
monitoring approach to periodic verification initiatives.
12
BMTS provided. On May 7, 2007, BMTS received a response from the Agency that
reiterated its prior position.
6
A true and correct copy of the Agency's April 4, 2007
Letter is attached hereto as Exhibit C. The Agency's representative referred BMTS to
Agency attorney Bill Ingersoll, who in turn referred BMTS to the Agency Attorney, Kyle
Davis.
From May 8, 2007 through early June 2007, BMTS exchanged correspondence
with Mr. Ingersoll regarding the IET. A true and correct copy of the e-mail
correspondence between BMTS and Mr. Ingersoll is attached hereto as Exhibit D. Mr.
Ingersoll recognized that the Chemical Indicator was not commercially available.' Even
so, Mr. Ingersoll stated that "it seems that we are unable to help you . . ."
See
Exhibit D.
Pursuant to the suggestion of Mr. Ingersoll, BMTS filed a Variance Petition on or about
June 24, 2007. (The Variance Petition was subsequently dismissed on July 26, 2007).
On August 24, 2007, BMTS and IEPA and Agency Attorney Kyle Davis,
discussed concerns related to the pending Variance Petition. Dr. Marsden participated in
this teleconference to try to answer specific technical questions on the appropriateness of
the use of the Certified Indicator in the KSU Efficacy Study. As an outcome of this
conference, BMTS agreed to provide additional information supporting the assertion that
the Certified Indicator is the preferred and most appropriate biological indicator organism
for the validation of dry heat sterilization processes.
6
Although the Agency's letter was dated April 4, 2007, which appears in a different type-font than the rest
of the letter, BMTS received the letter on May 7, 2007.
7
The Chemical Indicator cannot be purchased in a certified form. However, it is available in freeze-dried
form, which would require the purchaser to grow a viable population. However, this method necessitates
that the purchaser conduct rigorous testing to certify that the custom-grown population has the proper
resistance properties to validate a treatment process. In most cases, the purchaser will have to grow and
test several populations in order to certify a custom-grown population.
13
Dr. Daniel Y.C. Fung, an internationally known food, environmental and public
health microbiologist, and authority in the field of sterility control, reviewed the body of
scientific literature and provided an assessment on the appropriateness on the use of the
proposed Adjusted Standard for the validation of the Demolizer® technology.
Specifically, Dr. Fung concludes:
"Based on the overwhelming evidence, it is my expert opinion that
Bacillus
subtilis var. niger
(ATCC 9372, also known as
Bacillus atrophaeus)
is the
most
appropriate
biological indicator organism for the validation of dry heat
sterilization technologies. This specific subspecies of
Bacillus subtilis
demonstrates excellent growth and dry heat resistance characteristics. Standards
for performance have been established by USP, ISO, and others to ensure that
certified biological indicators for dry heat sterilization deliver predictable and
standardized resistance.
The Demolizer® technology is an alternative infectious waste treatment system
that employs dry heat as the sterilization agent. As such, the most appropriate
biological indicator organism for the validation of the efficacy of the Demolizer®
technology is the ISO and USP recognized standard,
Bacillus subtilis
var.
niger
(also known as
Bacillus atrophaeus).
Further, certified carriers manufactured
under rigorous quality standards should be used, wherever possible, since such
carriers are tested for purity and performance meeting defined D-value and z-
value performance criteria."
Letter from Dr. Daniel Y. C. Fung to Diane Gorder, August 27, 2007, a true and correct
copy of which is attached hereto as Exhibit G.
14
Dr. Fung has published extensively in Food Microbiology, Applied Microbiology
and Rapid Methods with more than 700 Journal articles, meeting abstracts, proceeding
papers, book chapters and books in his career. He has served as the major professor for
more than 90 M.S. and Ph.D. graduate students. The Kansas State University Rapid
Methods and Automation in Microbiology Workshop, directed by Dr. Fung, has attracted
more than 3,500 participants from 60 countries and 46 states to the program in the past 27
years. Dr. Fung is a Fellow in the American Academy of Microbiology, Institute of Food
Technologists (IFT), International Academy of Food Science and Technology and
Institute for Food Science and Technology (UK). He has won more than 30 professional
awards which included the International Award from IFT (1997), Waksman Outstanding
Educator Award from The Society of Industrial Microbiology (2001), KSU College of
Agriculture Excellence in Graduate Teaching Award (2005), and the Exceptional
Achievement and Founder of the KSU International Workshop on Rapid Methods and
Automation in Microbiology Award given by the Director of the Center for Food Safety
and Applied Nutrition, U.S. Food and Drug Administration, 2005. Dr. Fung received the
B.A. degree from International Christian University, Tokyo, Japan in 1965, M.S.P.H. at
University of North Carolina-Chapel Hill in 1967, and the Ph.D. in Food Technology
from Iowa State University in 1969. He is currently a Professor of Food Science,
Professor of Animal Sciences and Industry and Ancillary Professor of Biology at Kansas
State University and Distinguished Professo,r Universitat Autonama de Barcelona, Spain.
Based on all of this information, the Agency has agreed to recommend to the
Board that it grant this Petition for an Adjusted Standard.
15
VI.
Difficulties Meeting 35 IAC
§
1422.Table B
In developing the specific protocol used for demonstrating treatment efficacy,
BMTS attempted to acquire the Chemical Indicator in a certified carrier form.
Unfortunately, this subspecies is not available commercially in a certified carrier form.
With the help of researchers at Kansas State University, BMTS reviewed a
comprehensive scientific literature survey and identified an equivalent subspecies, the
Certified Indicator, as the industry standard for the validation of dry-heat sterilization
processes. The overwhelming use of the Certified Indicator as the preferred and most
appropriate indicator organism for dry-heat processes stems from its demonstrated
excellent dry heat resistance compared to dry heat sterilization compared to other
B.
subtilis
organisms.
See
Exhibit G, Letter from Dr. Daniel Fung, and Group Exhibit H,
Gurney, et al for expanded discussion on the appropriateness of the Certified Indicator for
the validation of dry heat sterilization processes. The Certified Indicator is cited in
numerous national and international standards including the U.S. Pharmacopoeia, the
International Standards Organization, and over three dozen scientific papers related to the
validation of sterilization processes.
See
Group Exhibit H,
infra.
BMTS made the decision to use the Certified Indicator because: 1) the indicators
are phenotypically identical with the exception of pigmentation response; 2) the Certified
Indicator is nearly universally recognized as the appropriate indicator microorganism to
demonstrate the effectiveness of thy-heat treatment processes, the underlying treatment
technology of the Demolizer® system; and 3) use of a Certified Indicator comports with
the best practices of the scientific community since Custom Indicator populations must be
grown in more non-controlled laboratory environments where it is possible to
16
inadvertently compromise the resistance and growth properties. Each manufacture must
test all production lots against stringent dry heat resistance performance standards as
expressed in D-values and z-values. Since the Certified Indicator is indisputably
recognized as the most appropriate
Bacillus
indicator organism for dry heat sterilization
processes and considered superior, from a heat resistance perspective, to the Chemical
Indicator and, unlike the Chemical Indicator, is available in a certified form that comports
with the industry's best practices, BMTS used the Certified Indicator in the KSU Efficacy
Test.
VII. Description of Efforts Necessary for BMTS to Achieve Immediate
Compliance
35 IAC 104.406(e) requires that the Petition contain a description of the efforts
required to come into immediate compliance. Under the Agency's current interpretation
of the Board's regulations, it is impossible for BMTS to achieve immediate compliance,
which could take as long as two and a half years due to the time and resources required to
grow and certify a Chemical Indicator to the same standards already demonstrated in the
KSU Efficacy Test. However, BMTS has already conducted a successful IET using the
preferred and most appropriate
Bacillus subtilis
indicator microorganism with a dry heat
resistance, understood in the scientific community, to be superior to that of the specific
species identified in the regulations. Therefore, if the Board were to accept the proposed
Adjusted Standard recognizing the overwhelming evidence in the scientific community,
BMTS would be in immediate compliance with the Board's regulations.
17
VIII. Immediate Compliance Would Impose an Arbitrary and Unreasonable
Hardship
35 IAC 104.406(e) requires that BMTS set forth reasons why immediate
compliance with the regulation would impose arbitrary and unreasonable hardship. Table
B's requirement of using a Chemical Indicator over a Certified or Dry Heat Indicator is
inappropriate and would impose an arbitrary and unreasonable hardship because it does
not take into consideration the body of scientific evidence that unequivocally supports the
claim that the Certified Indicator is most appropriate due to enhanced heat resistance
under dry heat conditions.
Further, 35 IAC 1422 has not been updated to include the Certified Indicator as an
equivalent alternative
B. subtilis
organism for the validation of dry heat and gas
sterilization technologies consistent with the market availability of such sterilization
technologies and the consensus within the standards and scientific community. At the
time of the adoption of 35 IAC 1422, prevalent sterilization technologies included
incineration, steam sterilization, chemical disinfection and radiation. The selection of the
specific subspecies in Table B are appropriate and consistent with scientifically
recognized indicator organisms for these traditional sterilization processes but are
inconsistent with domestic and international standards for the qualification of dry heat
treatment processes. These international standards promulgated by the US
Pharmacopoeia, International Standards Organization, the U.S. Food and Drug
Administration, the European Pharmacopoeia Commission, and others are the primary
reason why
B. subtilis
is only available commercially both domestically and
internationally as the Certified Indicator used in the KSU Efficacy Study.
18
Most states modeled their statutes and regulations off of a report titled
Technical
Assistance Manual: State Regulatory Oversight of Medical Waste Treatment
Technologies
that was prepared by the State and Territorial Association on Alternate
Treatment Technologies (the "STAATT Report"). 8 True and correct portions of the
STAATT Report are attached hereto as Exhibit E. The STAATT Report identified the
Chemical Indicator strain as a representative example of
Bacillus subtilis.
However, the
STAATT Report stressed that the Chemical Indicator spore was only a representative
strain of the species and was not selected based on any special resistance properties.
Further, the STAATT Report stated that "the guidelines developed through this series of
meetings should serve only to provide guidance to states in the development of a review
and approval process for medical waste treatment technologies." Exhibit E, STAATT
Report at p. 3.
As explained by Dr. Nelson S. Slavik, the primary author of the STAATT Report,
BMTS' "selection of
B. subtilis
ATCC 9372 spores is consistent with the criteria
provided by STAATT in their publication. This strain [the Certified Indicator] provides
the dry-heat resistance which is appropriate for your treatment process." Letter from
Nelson S. Slavik to Diane Gorder, June 11, 2007, a true and correct copy of which is
attached hereto as Exhibit F.
This opinion is supported by Dr. Daniel Y. C. Fung, internationally renowned
microbiologist.
See
Section V-C of this Petition and Exhibit G for a review of Dr. Fung's
analysis on the appropriateness of the Certified Indicator. The 35 IAC 1422 requirements
8
The STAATT Report was a culmination of conferences and debates beginning in 1992, the conclusions of
which were widely disseminated prior the publication of the final STAATT Report in April 1994.
19
that dry-heat based sterilization processes use the Chemical Indicator as opposed to the
Certified or Dry Heat Indicator in the IET is clearly arbitrary.
Moreover, BMTS will incur significant and unreasonable costs if it is required to
repeat the KSU Efficacy Test using a different colored indicator microorganism that is
likely to exhibit inferior heat resistance in a dry heat sterilization process. After learning
of the Agency's position, BMTS requested that KSU prepare an estimate to repeat the
KSU Efficacy Test using the Chemical Indicator to the same quality standards as attained
in the original KSU Efficacy Study. In preparation of this estimate, BMTS again
contacted Dr. Marsden, who would be responsible for repeating the study. Dr. Marsden
informed BMTS that, in order to grow a custom indicator and ensure comparable quality
standards to the previously conducted study using a certified carrier, the study would
require two major phases.
The first phase would involve growing a culture population of the Custom
Indicator and certifying its resistance properties through exhaustive D-value studies.
9 Dr.
Marsden would use standard protocols for validating the resistance of the culture similar
to those used throughout the industry. This study will likely need to be repeated several
times until a population is grown to the standards comparable to a Certified Indicator like
those obtained from certified manufactures.
Dr. Marsden provided an estimate of a minimum of $60,000 for a single D-value
evaluation of a population. It is very possible that repeated trials could result in a
total
cost approaching $250,000
to properly certify the population with a
total time frame of
up to two
years.
These estimates are phase-one costs only.
9
An organism's D-value is the treatment time required for 90% deactivation (sterilization), i.e.,
a
measure
of an organism's resistance to a particular treatment method - here, dry-heat.
20
Once a Custom Indicator population has been grown and certified, Dr. Marsden
would begin the second phase, which involves repeating the Demolizer® efficacy study
using appropriate replicates, load conditions, etc. This requires a
minimum of 2-4
months
to coordinate and report the study. Upon completion of both phases, validation
results comparable to those already reported could be obtained. The estimate provided by
Dr. Marsden for phase two of the validation study using ATCC 19659 is $40,000. In
addition to these costs, BMTS would incur
direct costs totaling more than $30,000,
which includes the cost of three dedicated systems and the cost of BMTS staff time to be
on-site at Kansas State University to facilitate the trial.
Therefore, the total cost for repeating the efficacy study using a Custom
Indicator is estimated to be between $130,000 and $320,000 dollars and could take
up to
two
and a half years to complete.
A true and current copy of the estimate is
found in Exhibit J. This information was also provided to the Illinois Bureau of Land in
September 2007 in support of the agency's review of this petition. BMTS would have to
sell numerous additional Demolizer® units to make up for the cost of repeating the IET
with the Chemical Indicator. Given that the Certified Indicator is reported to demonstrate
greater heat resistance than other
Bacilus subtilis
isolates, requiring BMTS to repeat the
same efficacy test using a Chemical Indicator is an arbitrary and unreasonable hardship.
Further, BMTS envisions continuous improvements of the technology which may
necessitate future IET trials to validate such improvements have not adversely impacted
treatment efficacy. The Certified Indicator is the scientifically recognized and widely
accepted indicator organism for the validation of the Demolizer® technology. If the
Adjusted Standard is not granted, BMTS will continue to incur substantial ongoing costs
21
to conduct efficacy studies using two similar and likely equivalent organisms, the
Certified Indicator and the Chemical Indicator organisms. Such duplicate effort is not
scientifically justified and is an arbitrary and unreasonable hardship.
IX.?
Narrative Description of the Proposed Adjusted Standard
35 IAC 104.406(0 requires that the Petition provide a narrative description of the
proposed adjusted standard
as
well as proposed language for a Board order that would
impose the standard. The Adjusted Standard would simply involve formally recognizing
the appropriateness of both the Certified and Chemical Indicators in Table B of 35 IAC
1422 for the validation of dry heat and chemical sterilization processes, respectively. The
proposed language for a Board order would involve amending Item 1 of Table B from "1.
Bacillus subtilis (ATCC 19659)" to "1. Bacillus subtilis (ATCC 19659) or Bacillus
atrophaeus (ATCC 9372)". This language recognizes the recent change in classification
of this particular isolate of Bacillus subtilis.
35 IAC 104.406(0 further requires the Petition to describe efforts necessary to
achieve this proposed standard and the corresponding costs must also be presented.
BMTS has already completed an Initial Efficacy Test demonstrating a 6 log
i o reduction
of
B. atrophaeus
(ATCC 9372) under varying load conditions. Thus, no additional
efforts are required by the Petitioner if the proposed standard is adopted.
22
X.
No Environmental Impact
35 IAC 104.406(g) requires that the Petition describe the quantitative and
qualitative description of the impact of the petitioner's activity on the environment if the
Petitioner were to comply with the regulation of general applicability as compared to the
quantitative and qualitative impact on the environment if the Petitioner were to comply
only with the proposed Adjusted Standard. BMTS' activities, operating under either the
regulation of general applicability or the proposed Adjusted Standard, have no adverse
impact on human, plant, or animal life. This is established by the studies described
herein. There are no emissions, discharges or releases from the use of the Demolize®
technology. All infectious waste treated in a Demolizer® system meets the requirements
for sterilization and final disposal outlined in the regulations.
XI.
Justification for the Adjusted Standard
35 1AC 104.406(h) requires that the Petition explain how the Petitioner seeks to
justify, pursuant to the applicable level of justification, the proposed adjusted standard.
As presented in Section IV of this Petition, the regulation of general applicability does
not describe a specific level of justification therefore the level of justification outlined in
35 IAC 104.426 applies. The following outlines a statement of justification for each of
the four conditions outlined in 35 IAC 104.426.
A.
Change in Factors Relied Upon by the are Substantially Different
35 104.426(a)(1) requires that the Petitioner demonstrate that factors relating to that
petitioner are substantially and significantly different from the factors relied upon by the
Board in adopting the general regulation applicable to that petitioner. At the time the
23
Illinois regulations were drafted (1992-1993), infectious waste treatment technologies
available both domestically and internationally primarily consisted of autoclave or steam
sterilization, chemical disinfection, and radiation. The Agency identified scientifically
recognized indicator organisms for these classes of sterilization technologies.
Bacillus
stearothermophilus
is the internationally recognized indicator organism for the validation
of steam sterilization technologies in the same manner that the Certified Indicator is the
USP and ISO recognized indicator organism for dry heat.
Bacillus subtilis
(ATCC
19659), the Chemical Indicator, is commonly used for the validation of chemical
disinfection processes, disinfectants and handwashing procedures.
Bacillus pumilis
is
generally recognized as the appropriate indicator organism for radiation sterilization
technologies. During the time period of the adoption of the Illinois regulation, the
STAATT committee, a group of state regulatory personnel and infection control
scientists, strongly recommended that the specific subspecies
(Bacillus subtilis, Bacillus
stearothermophilus, and Bacillus pumilis)
are for example purposes only and should not
be integrated directly into regulations since future technologies may warrant the use of
better suited indicator organisms. Section VIII and Exhibit F hereto provides additional
supporting evidence to this effect.
In the late 1990s, the Demolizer® technology and other dry heat based systems were
formally introduced in the United States for the treatment of infectious wastes. The
regulations were, in fact, promulgated in 1993 before the Demolizer technology was
formally introduced. Further, published standards for the validation of dry heat
sterilization technologies both domestically and internationally converged on the
selection of the Certified Indicator in the mid to late 1990s as the most appropriate
24
indicator organism for the validation of such technologies. The specific selection of
biological indicators in Table B is consistent with chemical disinfection, steam
sterilization, and radiation-based technologies. Table B does not, however, include the
Certified Indicator which is specifically optimal for the validation of dry heat sterilization
processes.
The Agency acknowledged that an Adjusted Standard may be necessary to address
emerging technologies in the Second Notice for Rulemaking (R91-20) published on
March 25, 1993. On Pages 19 and 20 of this Notice, the Agency specifically cites the
following:
"The record shows that the Study Group and the Agency proposed these provisions to
allow easy consideration for new technologies that do not fit the definition of chemical,
thermal or irradiation treatment. The Board supports this concept." (Note, dry heat is not
specifically listed in the definition of thermal treatment provided in the regulation.)
"The Board emphasizes that it is sympathetic with the concerns of the Agency
regarding the administrative burden of adjusted standards. An adjusted standard
proceeding is resource consuming not only for the Board, but for the Agency and the
petitioning party as well. Accordingly, reliance on the adjusted standard process must be
contemplated with care that an unnecessary and onerous administrative burden is not
created."
"By requiring the Board to grant adjusted standards consistent with Section 27(a), the
statute requires the Board to consider the implications of certain site-specific conditions
when granting an adjusted standard. As long as information requirements are met to the
extent applicable, a technology-specific adjusted standard may be granted."
25
Therefore, at the time of adoption of the general regulation, dry heat sterilization had
not been adapted for the treatment of infectious waste and was not included in the
definition of thermal treatment. In the late 1990s, the Demolizer® and other dry heat
treatment technologies became available in the U.S. and the international community.
The specific organisms listed in Table B of 35 IAC 1422 are consistent with technologies
available in the U.S. in the early 1990s. Table B, however, is not consistent with the
application of dry heat to treat infectious waste. The Agency and the Board envisioned
that adjusted standards may be warranted to include alternative biological indicators on a
technology-specific basis. Therefore, the absence of dry heat alternatives at the time of
drafting of the regulations is a factor that is substantially and significantly different than
factors existing today and warrant adoption of a technology-specific, adjusted standard.
B. Existence of Those Factors Justifies an Adjusted Standard
35 104.406(a)(2) requires that the Petitioner demonstrate that existence of such
factors justifies an adjusted standard. As stated above, 35 IAC 1422 is not consistent
with the large body of scientific evidence for the selection of appropriate indicator
microorganisms for the validation of dry heat medical waste treatment technologies. The
scientific consensus in the domestic and international scientific community and the
overwhelming body of evidence justify the use of the Certified Indicator for the
validation of dry heat sterilization technologies. Use of a different indicator organism,
such as
B. stearothermophilus
or
B. pumilis, are
not recognized in the scientific
community for the validation of dry heat technologies. The Chemical Indicator,
Bacillus
subtilis
(ATCC 19659) is recognized in the scientific literature for the verification of
chemical disinfectants, chemical disinfectant processes and hand washing procedures.
26
The Chemical Indicator is not recognized in the scientific community for the validation
of dry heat treatment processes. Similarly,
Bacillus atrophaeus
(ATCC 9372), the
Certified or Dry Heat Indicator, is the biological indicator of choice for dry heat
sterilization technologies due to its enhanced heat resistance under such conditions.
Further, the use of certified carriers for the validation of sterilization technologies
represents best practices in the scientific community since such certified carriers are
manufactured under strict international standards for quality and certification. The
Chemical Indicator is not commercially available in a certified form, thus insistence on
the use of a carrier that is not recognized for the validation of dry heat technologies and
must be grown under non-controlled conditions actually results in a lower quality result.
For these reasons, the factors presented hereto justify the proposed Adjusted Standard.
C.
No Environmental or Health Effects
35 104.406(a)(3) requires that the Petitioner demonstrate that the requested standard
will not result in environmental or health effects substantially and significantly more
adverse than the effects considered by the Board in adopting the rule of general
applicability. The extensive body of scientific evidence presented herein provides proof
that the proposed Adjusted Standard has no adverse environmental or health effect
compared to the standard stipulated in the regulation of general applicability. In fact, the
proposed Adjusted Standard is more beneficial. The proposed Adjusted Standard, the
Certified Indicator, poses a more difficult challenge for the Demolizer® technology than
the Chemical Indicator. BMTS has demonstrated that the Demolizer® technology
delivers a minimum 6 log /0
reduction of the Certified Indicator consistent with the
regulatory disinfection standard.
27
D. Consistency with Applicable Federal Law
35 IAC 104.406(a)(4) requires that the Petitioner demonstrate that the adjusted
standard is consistent with any applicable federal law. The treatment of infectious waste
and the approval of alternative treatment technologies are not regulated at the federal
level. However, state, federal, and international authorities recognize the use of the
Certified Indicator as an appropriate indicator microorganism for dry heat sterilization
validation procedures.
BMTS' Demolizer® devices have been approved or meet statutory requirements
in 46 states based on the results of the KSU Efficacy Test. While some of the states that
have approved Demolizer® technology do not specify a particular strain of indicator
microorganism, e.g., California, New York, Michigan, Connecticut, North Carolina,
South Carolina, Georgia, and Louisiana, others such as Florida specify only that the
species
B. subtilis
be used to validate sterilization treatments. Of the three states that
particularly identify the Chemical Indicator in their regulations, Arizona, Delaware, and
Illinois, BMTS has already received approval from both Arizona and Delaware based on
the KSU Efficacy Test. The State of New Mexico regulations have recently been
updated effective August 2, 2007. The previous draft of the New Mexico Administrative
Code, Solid Waste Regulations cited the
B. subtilis
ATCC 19659 (the Chemical
Indicator) as an indicator organism to demonstrate initial efficacy of alternative treatment
technologies. In the recently amended N.M.A.C. 20.9.8.13, the State of New Mexico
specifically recognizes
Geobacillus stearothermophilus
or
Bacillus atrophaeus
(the
Certified Indicator) as appropriate and scientifically recognized indicator organisms for
28
the validation of alternative technologies consistent with the facts and the evidence of
scientific consensus described hereto.
The federal government recognizes the appropriateness of using the Certified
Indicator to validate sterilization procedures. The U.S. Food and Drug Administration
identifies the Certified Indicator as the appropriate test organism for dry-heat based
sterilization procedures.
See
Group Exhibit H,
Guidance on Premarket Notification
[510(k)] Submissions for Sterilizers Intended for Use in Health Care Facilities
(March
1993);
Guidance on Premarket Notification [510(k)] Submissions for Sterilizers Intended
for Use in Health Care Facilities; Draft Guidance for Industry and FDA Reviewers
(May
2001),
supra.
In addition, the U.S. Pharmacopeia states that an appropriate biological
indicator for dry-heat sterilization should "compl[y] substantially with the morphological,
cultural, and biochemical characteristics of the strain of
Bacillus subtilis,
ATCC No.
9372 [the Certified Indicator], designated subspecies
niger . . ."
Group Exhibit H, U.S.
Pharmacopeia, Monographs: Biological Indicator for Dry-Heat Sterilization, Paper
Carrier, USP28-NF23 USP (2005),
infra.
Moreover, the international community has identified the Certified Indicator as
the standard indicator microorganism for validating dry-heat processes. For example, the
British Pharmacopoeia, the European Pharmacopoeia, the Japanese Pharmacopoeia, and
the International Organization for Standardization all list the Certified Indicator
as
the
biological indicator to validate dry-heat sterilization treatments. The world-wide
acceptance of the Certified Indicator
as
the industry standard further supports BMTS'
assertion that the Certified Indicator is the most appropriate organism for the validation
of dry heat sterilization technologies.
29
XII.
Consistency with Federal Law
35 IAC 104.406(i) requires that the Petition provide supporting reasons that the Board
may grant the proposed standard consistent with federal Law. Section XI-D of this
Petition provides such a statement. Infectious waste treatment standards are not governed
at the federal level. There are no procedural requirements applicable to the Board's
decision on the petition that are imposed by federal law.
XIII. Supporting Documents
35 IAC 104.406(k) requires that the Petition cite supporting documents and legal
authority. With respect to documents, Exhibits A through I are attached to this Petition
and are specifically referenced herein. In addition, for the convenience of the Board, true
and correct copies of relevant portions of the scientific authorities cited in this Petition
are attached collectively hereto as Group Exhibit H. The scientific literature discussed in
this Petition establishes that the Chemical and Certified Indicators are very similar°, if
10
1n
the scientific community, both the Certified and Chemical Indicators have been used to demonstrate
efficacy of a particular sterilization technology. The two substrains are very similar with the exception of
pigmentation response to certain culture conditions and, prior to 2004,
were
classified in the same
Bacillus
species. Nakamura and others state that, "Ielxcept for colour of the soluble pigment, all of the strains were
indistinguishable by the standard characterization method; i.e., they exhibited the traits typical of
B.
subtilis."
Group Exhibit Nakamura,
supra.
Blackwood reported that the RNA sequences of various
substrains of
B. subtilis are
indistinguishable with a reported sequence mapping of over 99%.
See
Group
Exhibit H, Blackwood,
supra.
Moreover, Blackwood also reported that the only way to differentiate
between the substrains would be to observe oxidative activity since they are identical with the exception of
pigmentation differences.
See id.
In 2000, the European Commission Health and Consumer Protection
Directorate-General stated that
"B. atrophaeus
is distinguishable from
B. subtilis
only by pigmentation."
Group Exhibit H, European Commission, Health and Consumer Protection Directorate-General,
Opinion of
the Scientific Committee on Animal Nutrition on the Safety of Use of Bacillus Species in Animal Nutrition
(Feb. 17, 2000).
Both strains have been used in the validation studies for various oxidative sterilization technologies. In
all cases, there was no reported difference in the performance of the two substrains. The Chemical
Indicator is broadly used for the validation of disinfectants and chemical disinfection processes. The
Certified Indicator is broadly
used
and recognized
as the
preferred indicator organism for dry heat
sterilization processes due to its demonstrated superior dry heat resistance. The Certified Indicator is also
recognized for the validation of certain gas sterilization technologies, including ethylene oxide disinfection.
See generally,
Group Exhibit IT;
see Gurney and Quesnel, see
U.S. Food and Drug Administration,
Guidance on Premarket Notification [510(k)] Submissions for Sterilizers Intended for Use in Health Care
Facilities
(March 1993) (listing both the ATCC 9372 and the ATCC 19659
B. subtilis
samples as
30
not equivalent, with the Certified Indicator recognized internationally as the
most
appropriate
biological indicator for the validation of dry heat sterilization processes.
Most importantly, Gurney and Quesnel established that the Certified Indicator is
the preferred biological microorganism for the validation of dry heat treatment processes
in a definitive comparative study. This work surveyed the compendium of published
literature on dry heat resistance of
Bacillus subtilis
spores. Further, the authors
completed extensive comparative resistance studies on the Certified Indicator and a
generic
Bacillus subtilis
organism, typical of the Chemical Indicator, over a temperature
range of
140
to
170°C.
At all temperatures, the Certified Indicator demonstrated superior
heat resistance properties. Group Exhibit H, Gurney, T.R. & Quesnel, L.B.,
Thermal
Activation and Dry-heat Inactivation of Spores of Bacilus subtilis MD2 and Bacillus
subtilis var. niger, J.
APPLIED BACTERIOLOGY,
48, 231-247 (1980).
The following domestic and international standards list the Certified Indicator for
the validation of dry-heat processes. Each standard is developed by an expert panel of
equivalent indicator organisms to validate dry-heat sterilizers);
see also
U.S. Food and Drug
Administration,
Guidance on Premarket Notification 11510(k)] Submissions for Sterilizers Intended for Use
in Health Care Facilities; Draft Guidance for Industry and FDA Reviewers (May
2001) (updated
publication listing only the Certified Indicator (ATCC 9372) to validate dry-heat sterilization treatments).
In a 2004 Environmental Technology Verification Report conducted by Battelle, both the Chemical
and Certified Indicators were used to validate the effectiveness of a formaldehyde-based decontamination
technology, and there were no reported qualitative differences in the resistance of the two samples.
See
Group Exhibit H, Battelle,
Environmental Technology Verification Report prepared for CERTEK, Inc.
(Aug. 2004).
In a 2001 comparative study by Khadre and Yousef, the resistance of both the Certified and Chemical
Indicators were shown to be equivalent during an evaluation of ozone and hydrogen peroxide sterilization
technologies.
See
Group Exhibit H, M.A. Khadre, A.E. Yousef,
Sporicidal Action of Ozone
and Hydrogen
Peroxide: A Comparative Study,
INT'L. J. OF
FOOD MICROBIOLOGY,
71, 131-138 (2001). In fact, IChadre
and Yousef concluded that "differences among these strains were not significant (p<0.05)."
Id.
Similarly, in a study by Sagripanti,
et at,
the Chemical and Certified Indicators were evaluated along with
other various strains for sporicidal activity against a broad range of oxidative treatment technologies and
found
to have resistances "within I Log
i°
of each other." Group Exhibit H, .1
-L. Sagripanti,
et al., Virulent
Spores of Bacillus Anthracis and other Bacillus Species Deposited on Solid Surfaces Have Similar
Sensitivity to Chemical Decontaminants, J.
APPLIED MICROBIOLOGY,
102, 11-21 (2007).
31
microbiologists and sterility assurance specialists who review the body of scientific and
published literature to make recommendations based on overall resistance of organisms
to a specific sterilization technology. Manufacturers of certified carriers, such as those
used in the KSU Efficacy Study, must test each production lot of carriers to meet specific
heat resistance targets, as measured in D-value and z-values under specific conditions, to
ensure the proper standardization.
1.
US
Pharmacopoeia.
USP28-NF23 USP. Monographs: Biological Indicator for
Dry-Heat Sterilization, Paper Carrier; Rockville, MD; 2005.
2.
FDA. Guidance on Premarket Notification [510(k)] Submissions for Sterilizers
Intended for Use in Health Care Facilities. Infection Control Devices Branch,
Division of General and Restorative Devices (March 1993).
3.
FDA. Premarket Notifications [510(k)] for Biological Indicators Intended to
Monitor Sterilizers Used in Health Care Facilities; Draft Guidance for Industry
and FDA Reviewers; U.S. Department of Health and Human Services, Food and
Drug Administration, Center for Devices and Radiological Health, Infection
Control Devices Branch (March 2001).
4.
British Pharmacopoeia Commission.
Methods of sterilization. London, UK:
British Pharmacopoeia Commission; British Pharmacopoeia Appendix XVIII
(2003).
5.
European Pharmacopoeia Commission.
Biological indicators of sterilization.
Strasbourg, France: European Pharmacopoeia Commission; European
Pharmacopoeia EP 5.1.2 (1997).
6.
Japanese Pharmacopoeia.
JP14e.partI1.15 JP. Terminal Sterilization and
Sterilization Indicators.
7.
ISO and ANSI.
Sterilization of health care products — Biological indicators; Part
4: Biological indicators for dry heat processes. Geneva (Switzerland):
International Organization for Standardization/ANSI; ISO 11138-4:2006.
See
Group Exhibit H.
32
e of Its Attorneys
XIV. Affidavit Verifying Facts
The affidavit of BMTS' Director of Regulatory Compliance, Diane Gorder,
verifying both that the facts stated in this Petition are true and that the attached exhibits
are true and accurate copies, is attached hereto as Exhibit I.
CONCLUSION
BMTS
therefore asks that this Board, pursuant to its authority under Section 35 of
the Act and the Board's regulations under 35 IAC 104, grant BMTS an Adjusted
Standard from the provisions of 35 IAC 1422.Table B recognizing the Certified Indicator
as the most appropriate biological indicator organism for the validation of dry heat
sterilization technologies.
Specifically, BMTS requests that an Adjusted Standard be granted for the use of
Bacillus atrophaeus
(formerly
Bacillus subtilis var. niger,
also scientifically recognized
as ATCC 9372 or NRRL B4418) for the IET of dry heat treatment technologies.
Respectfully Submitted,
BIOMEDICAL TECHNOLOGY
SOLUTIONS, INC.
By:
Dated: January 7, 2008
Neal H. Weinfield
Jason B. Elster
GREENBERG TRAURIG, LLP
Firm No. 36511
77 West Wacker Drive, Suite 2500
Chicago, Illinois 60601
312-456-8400 (Telephone)
312-456-8435
(Facsimile)
weinfieldn@gtlaw.com
elsterj@gtlaw.com
33