5.2.1	Is the sample centrifuged at 1500 x G (maximum 2000 x G) using a swinging bucket rotor?
                      13.2.1     and       NOTE     pg 46
                      13.2.1     and      NOTE     pg 37
                                       -
                        Method Procedure            GLP

    5.2.2	Are the centrifuge tubes properly balanced prior to centrifugation?
                                       -
                                    13.2.1
                                    3.15.4
                                   Critical

    5.2.3	Does lab have easily accessible method for determining relative centrifugal force of centrifuges?
                                       -
                                       -
                                    3.15.1
                   Critical                             GLP

    5.2.4	Is the sample centrifuged for 15 minutes, with time beginning when centrifuge reaches desired speed?
                                    13.2.1
                                    13.2.1
                                       -
                               Method Procedure

    5.2.5	Is the centrifuge slowly decelerated at the end without the brake?
                                    13.2.1
                                    13.2.1
                                       -
                               Method Procedure

    5.2.6	Is the pellet volume determined?
                                    13.2.1
                                    13.2.1
                                     5.2.3
                                  Requirement

    5.2.7	Is there a set of standards for comparison of pellet size?
                                       -
                                       -
                                     5.2.3
                             Recommendation    GLP

    5.2.8	Are SOPs for Envirochek[(R)] and Filta-Max[(R)] filter sample centrifugation available in the work area, and does laboratory practice reflect written procedures?

                  Critical                               GLP

    5.2.9	Other than issues noted for items 5.2.1 through 5.2.8 (if any) was Envirochek[(R)] HV or Filta-Max[(R)] filter sample centrifugation demonstrated successfully?

6	          Purification and Slide Preparation
Technician:
6.1	Is an approved IMS kit/manufacturer used?
                                      7.5
                                     7.7.1
                                       -
                       Method Procedure             GLP

6.2	Is the supernatant from the centrifuged sample aspirated no lower than 5 mL of supernatant above every 0.5 mL pellet or portion of 0.5 mL pellet?
                                    13.2.2
                               13.2.2     13.2.3
                                5.2.2    5.2.3
                                  Requirement

    6.2.1	Are the samples aspirated using the pipette, with the documented internal diameter, as specified in the SOP?
                                       -
                               NOTE       pg 37
                                       -
                                   Critical

    6.2.2	Is the proper rate (mL/min) or pressure (psi) maintained throughout aspiration?
                                       -
                                13.2.2   13.2.3
                                       -
                               Method Procedure

6.3	Is the pellet vortexed a sufficient time for resuspension?
                         13.2.3   <IP_ADDRESS>.3  <IP_ADDRESS>
                        <IP_ADDRESS>  <IP_ADDRESS>.2  <IP_ADDRESS>
                                       -
                               Method Procedure

6.4	Is the resuspended pellet volume quantitatively transferred to the flat-sided tube (2 rinses)?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                       -
                               Method Procedure

6.5	Are the IMS beads thoroughly resuspended prior to addition to the flat-sided tube?
                               <IP_ADDRESS> <IP_ADDRESS>
                              <IP_ADDRESS>   <IP_ADDRESS>
                                       -
                               Method Procedure

6.6	Is the flat-sided tube rotated at 18 rpm for 1 hour at room temperature?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                       -
                               Method Procedure

6.7	Is the rotating mixer calibrated annually?
                                       -
                                       -
                                    3.17.4
                   Critical                              GLP

6.8	Is flat-sided tube correctly placed in magnet and rocked through 90 degrees about once per second?
                               <IP_ADDRESS>-<IP_ADDRESS>
                               <IP_ADDRESS>-<IP_ADDRESS>
                                       -
                               Method Procedure

6.9	Is all the liquid removed when decanting is performed with the magnet up?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                       -
                               Method Procedure

6.10	Is the sample quantitatively transferred from the flat-sided tube to the microcentrifuge tube (2 rinses)?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                       -
                               Method Procedure

6.11   Are the beads rinsed with PBS while inside the microcentrifuge tube?
                                    13.3.4
                                   <IP_ADDRESS>
                                       -
                              1623 Recommendation
                              1623.1 Requirement

6.12 	Is standard NaOH (5 uL, 1N) and standard HCl (50 uL, 0.1N) used?
                           NOTE      pg 49 & 50
                                NOTE      pg 42
                                    3.17.5
                      Requirement                     GLP

6.13	Is sample vortexed vigorously for 50 seconds immediately after the addition of acid and 30 seconds after the sample has set for 10 minutes at room temperature?
                               <IP_ADDRESS>-<IP_ADDRESS>
                               <IP_ADDRESS>-<IP_ADDRESS>
                                       -
                               Method Procedure

6.14	Is a second dissociation performed?
                           <IP_ADDRESS> NOTE     pg 49
                           <IP_ADDRESS>  NOTE     pg 41
                                     5.2.4
                                  Requirement

6.15	When the second dissociation is performed, does the laboratory:
	(A) use a second slide
          	(B) add the additional volume to the original slide?
                                   <IP_ADDRESS>
                               <IP_ADDRESS>  13.4.5
                                       -
                                  Circle one:
                                A             B

6.16	Are the slides clearly labeled so they can be associated with the correct sample?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                       -
                                  Requirement

6.17	What type of slides is used?

                                      GLP

6.18	Is slide dried at: (A) room temperature, (B) 35º to 42ºC, or (C) in the refrigerator?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                       -
                                 Circle one:
                               A       B       C

6.19	If the slide is warmed, is incubator or slide warmer calibrated and labeled?
                                       -
                                       -
                                      3.4
                 Critical                                 GLP

6.20	Are SOPs available in the work area for sample purification and slide preparation, and does laboratory practice reflect written procedures?

                  Critical                                GLP

6.21	Other than issues noted for items 6.1 through 6.20 (if any) was purification and slide preparation demonstrated successfully?

7          Sample Staining
Technician:
7.1	What staining kit/manufacturer is used?
                                     14.2
                                     14.2
                                    3.18.1
                                      GLP

7.2	Is FITC stain applied according to manufacturer's directions?
                                     14.2
                                     14.2
                                     5.3.2
                               Method Procedure

7.3	Are positive and negative staining controls performed?
                                     14.1
                                     14.1
                                     5.3.5
                                  Requirement

7.4	Are the slides incubated in a humid chamber in the dark at room temperature for approximately 30 minutes or per manufacturer's directions?
                                     14.3
                                     14.3
                                     5.3.3
                               Method Procedure

7.5	Are the labeling reagents rinsed away properly after incubation, without disturbing the sample?
                                     14.5
                                     14.5
                                       -
                               Method Procedure

7.6	Was the working DAPI stain prepared the day it was used?
                                     7.7.2
                                     7.9.2
                                    3.19.2
                               Method Procedure

7.7	Is stock DAPI stored at 1 to 10[o]C in the dark?
                                     7.7.1
                                     7.9.1
                                    3.19.1
                               Method Procedure

7.8	Is the DAPI stain applied properly and allowed to stand for a minimum of 1 minute?
                                     14.6
                                     14.6
                                       -
                               Method Procedure

7.9	Is the DAPI stain rinsed away properly without disturbing the sample?
                                     14.7
                                     14.7
                                       -
                               Method Procedure

7.10	Is the mounting media applied properly?
                                     14.8
                                     14.8
                                       -
                               Method Procedure

    7.10.1	What type of mounting media is used?
                                      7.8
                                     7.10
                                       -
                                      GLP

    7.10.2	Are all the edges of the cover slip sealed well with clear fingernail polish, unless Elvanol[(R)] is used?
                             7.9       14.9
                             7.11     14.9
                                       -
                               Method Procedure

7.11	Are the finished slides stored in a humid chamber in the dark at 1 to 10[o]C (humid chamber not required for Elvanol[(R)])?
                                     14.10
                                     14.10
                                     5.3.6
                               Method Procedure

7.12	Are SOPs for sample staining available in the work area, and does laboratory practice reflect written procedures?

                   Critical                              GLP

7.13	Other than issues noted for items 7.1 through 7.12 (if any) was sample staining demonstrated successfully?

8      	Microscope and Examination
8.1	Is microscope equipped with appropriate excitation and band pass filters for examining FITC labeled specimens as demonstrated with lab, and auditor provided, positive staining control?
                                     6.9.2
                                     6.7.2
                                    3.22.3
                      Requirement                    GLP

8.2	Is microscope equipped with appropriate excitation and band pass filters for examining DAPI labeled specimens as demonstrated with lab, and auditor provided, positive staining control?
                                     6.9.3
                                     6.7.3
                                    3.22.3
                    Requirement                         GLP

8.3	Does the microscope have appropriate objectives and filters for DIC, which change easily to and from epifluorescence?
                                     6.9.1
                                     6.7.1
                                    3.22.4
                      Requirement                    GLP

8.4	Are all portions of the microscope, from the light sources to the oculars, properly adjusted?
                                 10.3
                            10.0        Appendix B
                                    3.22.6
                                  Requirement

8.5	Is the DIC image appropriate for each laboratory microscope?
                                       -
                                   Figure 4
                                 Visual Guide
                                  Requirement

8.6	Is microscope cleaned after every session?
                                     10.4
                                    10.9.8
                                    3.22.11
                       Requirement                  GLP

8.7	Does the microscope have a 20X scanning objective?
                                     6.9.1
                                     6.7.1
                                    3.22.8
                      Requirement                    GLP

8.8	Does the microscope have a 100X oil immersion objective?
                                     6.9.1
                                     6.7.1
                                    3.22.8
                      Requirement                    GLP

8.9	Is the microscope equipped with an ocular micrometer?
                                     6.9.1
                                     6.7.1
                                    3.22.9
                       Requirement                   GLP

8.10	Is a stage micrometer available to laboratory?
                                 6.9.1 10.3.5
                               6.7.1    App. B 3
                                    3.22.9
                                  Requirement

8.11	Is a calibration table for 100X objective located close to the microscope(s)?
                                   <IP_ADDRESS>
                                  App. B 3.7
                                    3.22.9
                                  Requirement

8.12	Has the mercury bulb been used less than the maximum hours recommended by the manufacturer?
                                   <IP_ADDRESS>
                                  App.B 1.11
                                    3.22.12
                                  Requirement

8.13	Does the laboratory have a preventative maintenance agreement in place to service the microscope annually?
                                       -
                                       -
                                    3.22.6
                   Critical                             GLP

8.14	Are SOPs for sample examination available in the work area, and does laboratory practice reflect written procedures?

                   Critical                              GLP

8.15	Other than issues noted for items 8.1 through 8.13 (if any) was Microscope and Examination demonstrated successfully?

9		Positive Staining Control and OPR Slides
9.1	Does the laboratory's positive staining control slide contain (oo)cysts at the appropriate fluorescence intensity for FITC?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                            5.4.8 <IP_ADDRESS> <IP_ADDRESS>
                                  Requirement

9.2	Does the laboratory's positive staining control slide contain (oo)cysts at the appropriate fluorescence intensity for DAPI?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                            5.4.8 <IP_ADDRESS> <IP_ADDRESS>
                                  Requirement

9.3	Does the laboratory's positive staining control slide contain an appropriate level of background fluorescence?
                                       -
                                       -
                                     5.4.3
                                Recommendation

9.4	Is concentration of oocysts on the positive staining control slide appropriate?
                                14.1.1 <IP_ADDRESS>
                               14.1.1   <IP_ADDRESS>
                                    <IP_ADDRESS>
                                  Requirement

9.5	Does the laboratory's positive staining control exhibit appropriate contrast and organism features by DIC?
                                       -
                                   Figure 4
                                 Visual Guide
                                  Requirement

9.6	Does the laboratory's OPR slide contain (oo)cysts at the appropriate fluorescence intensity for FITC?
                               <IP_ADDRESS> <IP_ADDRESS>
                               <IP_ADDRESS> <IP_ADDRESS>
                               <IP_ADDRESS> <IP_ADDRESS>
                                  Requirement

9.7	Does the laboratory's OPR slide contain (oo)cysts at the appropriate fluorescence intensity for DAPI?
                               <IP_ADDRESS> <IP_ADDRESS>
                               <IP_ADDRESS> <IP_ADDRESS>
                               <IP_ADDRESS> <IP_ADDRESS>
                                Recommendation

9.8	Does the laboratory's OPR slide contain an appropriate level of background fluorescence?
                                       -
                                       -
                                     5.4.3
                                  Requirement

9.9	Does the laboratory's OPR slide exhibit appropriate contrast and organism features by DIC?
                                    <IP_ADDRESS>
                               <IP_ADDRESS> Figure 4
                                 Visual Guide
                                  Requirement

9.10	Does the technical auditor's count of Cryptosporidium oocysts and Giardia cysts on the OPR slide sent by the laboratory agree within 10% of laboratory count?
                                   <IP_ADDRESS>
                                   <IP_ADDRESS>
                                    <IP_ADDRESS>
                                  Requirement

Comments:

10	Onsite Sample Processing
                                  Method Step
                                     Name
                                   Position
                      Demonstrated Technique Successfully
                                    yes/no
Spiking  -  (filter type)

Filtration - (filter type)

Spiking flat-sided tube, and processing IMS control

Aspiration and transfer from 250 mL bottle

11	Onsite Blind Spike Results
                                    Sample
                              Crypto Spike Value
                                 Crypto Count
                              Crypto Recovery (%)
                              Giardia Spike Value
                                 Giardia Count
                             Giardia Recovery (%)

12	Evaluation of Onsite Sample Processing and Blind Spike Results  -  Comments and Recommendations
                                Classification
                                   Comments
                              Response Requested

13	Was analyst microscope operation acceptable? (yes/no)

                                  Requirement
                             Method 1623: <IP_ADDRESS>
                             Method 1623.1: 10.7.1
                                  Requirement
                            Method 1623: <IP_ADDRESS>-3
                            Method 1623.1: 10.7.2-3
                                  Requirement
                              Method 1623: 10.3.6
                              Method 1623.1: 10.8
                                     Name
                                   Position
                        Adjust Interpupillary Distance
                             Focus both eyepieces
                         Establish Kohler Illumination

14	Slide Count and Analyst Verification Results (yes/no)

                                  Requirement
                             Method 1623: <IP_ADDRESS>
                            Method 1623.1: <IP_ADDRESS>
                                  Requirement
                             Method 1623: <IP_ADDRESS>
                            Method 1623.1: <IP_ADDRESS>
                                  Requirement
                               Method 1623: 15.2
                              Method 1623.1: 15.2
                                  Requirement
                        Method 1623: <IP_ADDRESS>  <IP_ADDRESS>
                       Method 1623.1: <IP_ADDRESS>  <IP_ADDRESS>
                                  Requirement
                        Method 1623: <IP_ADDRESS>  <IP_ADDRESS>
                       Method 1623.1: <IP_ADDRESS>  <IP_ADDRESS>
                                    Analyst
                   Crypto Count Within 10% of Target Count
                   Giardia Count Within 10% of Target Count
                      Examine and Record Characteristics
                              Measurement (100X)
                       Demonstrated Internal Structures

15	Evaluation of Analyst Microscopy and Examination Skills   -  Comments and Recommendations
                                Classification
                                   Comments
                              Response Requested

                                  Appendix H

              Positive Staining Control and OPR Slide Evaluation

Laboratory Name:

Date:

Technical Auditor:

Organism/Slide ID:  Cryptosporidium

                                       1
                                       2
                                       3
                                       4
                                     Score
                            Positive Stain Control
Number of Organisms
[Sections 14.1.1 & <IP_ADDRESS> (Sections 14.1.1 & <IP_ADDRESS>)]
               organisms in very low numbers (<~25 oo/cysts)
                organisms in low numbers (~25 to ~100 oo/cysts)
        organisms in relatively high numbers(~100 to <~200 oo/cysts)
                 organisms in high numbers (>~200 oo/cysts)

           FITC Fluorescence*
[Section <IP_ADDRESS> (Section <IP_ADDRESS>)]
                 consistently weak (1+); inadequate; not crisp
inconsistent; more weak (1+)  than strong (3+); less than adequate; more not crisp than crisp
inconsistent;  more strong (3+) than weak (1+); adequate; more crisp than not crisp
                   consistently strong (3+); superior; crisp

           DAPI Fluorescence**
[Section <IP_ADDRESS> (Section <IP_ADDRESS>)]
DAPI negative in majority of oocysts; nuclei stained consistently weak (1+); inadequate
distinct nuclei in less than half of the oocysts; nuclei stain inconsistent; more weak (1+)  than strong (3+); less than adequate
distinct nuclei stained in majority of oocysts; nuclei stain inconsistent;  more strong (3+) than weak (1+); adequate
distinct nuclei stained in majority of oocysts; nuclei stain consistently strong (3+); superior

                            Background Fluorescence
                            excessive, interfering
                                  distracting
                         exists but does not interfere
                            minimal to nonexistent

                Background and Organism Characteristics on DIC
                             interfering; atypical
                             distracting; atypical
                    exists but does not interfere; typical
                        minimal to nonexistent; typical

                                      OPR
          Number of Organisms
[Section <IP_ADDRESS> (Section <IP_ADDRESS>)]
                     difference in number counted >20%
                               16-20% difference
                               10-15% difference
                     difference in number counted <10%

           FITC Fluorescence*
[Section <IP_ADDRESS> (Section <IP_ADDRESS>)]
                 consistently weak (1+); inadequate; not crisp
inconsistent; more weak (1+)  than strong (3+); less than adequate; more not crisp than crisp
inconsistent;  more strong (3+) than weak (1+); adequate; more crisp than not crisp
                   consistently strong (3+); superior; crisp

           DAPI Fluorescence**
[Section <IP_ADDRESS> (Section <IP_ADDRESS>)]
DAPI negative in majority of oocysts; nuclei stained consistently weak (1+), inadequate
distinct nuclei in less than half of the oocysts; nuclei stain inconsistent; more weak (1+)  than strong (3+); less than adequate
distinct nuclei stained in majority of oocysts; nuclei stain inconsistent;  more strong (3+) than weak (1+); adequate
distinct nuclei stained in majority of oocysts; nuclei stain consistently strong (3+), superior

                            Background Fluorescence
                            excessive, interfering
                                  distracting
                         exists but does not interfere
                            minimal to nonexistent

          Background and Organism Characteristics on DIC
[(Figure 4)]
     interfering; <50% of oo/cysts undamaged and morphologically intact
      distracting; <50% oo/cysts undamaged and morphologically intact
exists but does not interfere;  >50% oo/cysts undamaged and morphologically intact
 minimal to nonexistent; >50% oo/cysts undamaged and morphologically intact

*FITC  Fluorescence: brilliant apple-green ovoid or spherical objects with brightly highlighted edges (referred to as crisp above); compared for all organisms over complete well slide at 200x
**DAPI Fluorescence: light blue internal staining (no distinct nuclei) with green rim, intense blue internal staining, or distinct, sky-blue nuclei; compared for all organisms over complete well slide at minimum of 400x
Fluorescence intensity scale:  1+ = weak, 2+=medium, 3+=strong
For visual comparisons, see FITC and DAPI staining examples in Method 1623.1 Microscopy Visual Guide (p. 61 in Method 1623.1) or the LT2 On-line Microscopy Training Module (http://water.epa.gov/lawsregs/rulesregs/sdwa/lt2/compliance.cfm#training). For descriptions, see Method 1623/1623.1 Sections 15.2.2 and 15.2.3.
Section references in [  ] refer to EPA Method 1623, and the corresponding section references in parentheses and italics refer to EPA Method 1623.1.
Satisfactory scores are >= 3. Any score <= 2 (shown in red font) indicates problems with slide preparation and should be investigated. If slide evaluation is conducted as part of the Assessment of Cryptosporidium Laboratory Quality Assurance under the Safe Drinking Water Act, scores, comments and any requirements, recommendations, or commendations should be included in Section 9 of Checklist C - Method 1623/1623.1 Technical Review - Sample Processing and Microscopy.
Comments:
PSC:

OPR:
Requirements, Recommendations, Commendations:

                                  Appendix I

                 Example Report from Online Analyst Evaluation

                                  Appendix J

Method 1623 Ongoing Precision and Recovery (OPR) and Initial Precision and Recovery (IPR) Quality Control Criteria Calculated from Five Rounds of Proficiency Testing (PT) Data

Method 1623 Ongoing Precision and Recovery (OPR) and Initial Precision and Recovery (IPR) Quality Control Criteria Calculated from Five Rounds of Proficiency Testing (PT) Data
                             Updated July 9, 2013
Introduction
The December 2005 Method 1623 Ongoing Precision and Recovery (OPR) and Initial Precision and Recovery (IPR) quality control and acceptance criteria were developed based on 293 Cryptosporidium OPR samples and 186 Giardia OPR samples analyzed by six laboratories during the Information Collection Rule Supplemental Surveys from March 1999 to February 2000.  In 2009, the minimum Cryptosporidium percent recovery for OPR samples was updated based on analysis of data from the February and May 2007 proficiency testing (PT) rounds as published in the Federal Register (Federal Register Notice, Vol. 74, No. 36 February 25, 2009).
To more accurately reflect current laboratory capability and provide better values for assessment of laboratory performance, data from five PT rounds (February and May 2007, July 2009, February 2010, and March 2011) were used to develop quality control criteria.  For each round, laboratories analyzed three blind reagent water samples spiked with flow-cytometer counted organisms prepared by the Wisconsin State Laboratory of Hygiene.  These updated criteria provide a better assessment of laboratory capability than the 2009 values  for the following reasons: 1) the data set is more recent; 2) the sample size is more than twice as large as the 2009 sample size; and 3) the updated value of 33% for Cryptosporidium OPR samples is consistent with the Quality Control Acceptance Criteria developed with Method 1623.1 (EPA Method 1623.1, January 2012 (PDF) (83 pp, 1MB).  A summary of the data set and proposed acceptance criteria are shown in Table 1.
Calculation of OPR Minimum Recovery Criteria
The minimum Cryptosporidium percent recovery criteria for OPR samples were calculated based on data from the February and May 2007, July 2009, February 2010, and March 2011 PT rounds, which were all of the PT rounds with protozoan suspensions in reagent water without any additional matrix material.  The remaining PT rounds had matrix additions and would not simulate an OPR or IPR.  The acceptance criteria were calculated using data from labs approved and participating in the Lab QA Program as of June 24, 2011.  The calculated lower limit of recovery was 33% for Cryptosporidium and 29% for Giardia.  When applying the criteria to the data from the five PT rounds, 51 samples or 6.8% of the 753 samples did not meet the criterion for Cryptosporidium, and 31 samples, or 5.8% of the 530 samples, did not meet the criterion for Giardia.
Details of the Calculation of OPR Minimum Recovery Criteria
To calculate OPR recovery criteria, estimates of variance attributable to four different sources were calculated: variability between laboratories, variability between PT rounds, variability between laboratory-and-round (i.e., attributable to an interaction between round and laboratory), and variability within round and laboratory (i.e., analytical variability).  There were a few laboratories that performed PT analyses using multiple filters.  For the purpose of these calculations, the two sets of analyses were two separate entities; in other words, the two lab/filter combinations were treated as two different laboratories.  The different variance components were calculated using PROC MIXED from SAS version 8 using the maximum likelihood method of estimation on recovery data.  Details on the maximum likelihood estimation can be found in SAS/STAT User's Guide.
Estimates of between laboratory variance, between round variance, between laboratory-and-round variance, and within laboratory-and-round variance were labeled s[2]L, s[2]R, s[2]LR and s[2]w, respectively.
The combined standard deviation (sc) is:

	Where:
		 = average number of laboratory/filter combinations per round
	 = average number of rounds per laboratory/filter combination
	n = average number of replicates per laboratory/filter and round (3 for Cryptosporidium, 2.2 for Giardia)
	C = total number of laboratories/filters/rounds
      R = number of rounds (5)
	L = number of laboratory/filter combinations
Lower recovery limits for OPR samples were then calculated as:

		Where:
		Xmean =	the mean recovery of all samples
		t(0.95,df) = 95[th] percentile of the student's t distribution with df degrees of freedom
		df is calculated using Satterthwaite's estimate as given below:

Calculation of IPR Minimum Mean Recovery and Maximum RSD Criteria
The QC acceptance criteria for IPR samples were calculated based on data from the February and May 2007, July 2009, February 2010, and March 2011 PT rounds.  The calculated lower limit of recovery was 36% for Cryptosporidium and 32% for Giardia.  When applying the criteria to the data from the five PT rounds, 16 (6.4%) of the 251 round/filter/laboratory combinations did not meet the criterion for minimum mean recovery for Cryptosporidium, and 17 (7.1%) of the 240 combinations did not meet the minimum mean recovery criterion for Giardia.  The maximum RSD of 34% for Cryptosporidium and 37% for Giardia was also calculated using data from the five PT rounds.  Applying the criteria to the data from all laboratories, 14 laboratory/filter/round combinations (5.6%) did not meet the Cryptosporidium criterion and 14 combinations (5.8%) did not meet the Giardia criterion.  Six of the 16 Cryptosporidium lab/round/filter combinations and 5 of the 17 Giardia combinations that failed the lower recovery criterion also failed the precision criterion.  It is worth noting that because the criteria are calculated for 4 samples, while the data included only 3 (Cryptosporidium) or 2 (Giardia) results per lab, the failure rates would be expected to be greater than the target 5%.  However, due to the large number of laboratory/filter/round combinations, the failure rate was ≈5%.
Details of the Calculation of IPR Criteria
Similar to the calculations for the OPR recovery criteria, IPR recovery criteria were calculated with estimates of variance attributable to four different sources: variability between laboratories, variability between PT rounds, variability between laboratory-and-round (i.e., attributable to an interaction between round and laboratory), and variability within round and laboratory (i.e., analytical variability).  There were a few laboratories that performed PT analyses using multiple filters.  For the purpose of these calculations, the two sets of analyses were two separate entities; in other words, the two lab/filter combinations were treated as two different laboratories.  The different variance components were calculated using PROC MIXED from SAS version 8 using the maximum likelihood method of estimation on recovery data.  Details on the maximum likelihood estimation can be found in SAS/STAT User's Guide.
Estimates of between laboratory variance, between round variance, between laboratory-and-round variance, and within laboratory-and-round variance were labeled s[2]L, s[2]R, s[2]LR and s[2]w, respectively.
The combined standard deviation (sc) is:

	Where:
		 = average number of laboratory/filter combinations per round
	 = average number of rounds per laboratory/filter combination
      n = average number of replicates per laboratory/filter and round (3 for Cryptosporidium, 2.2 for Giardia)
	C = total number of laboratories/filters/rounds
	R = number of rounds (5)
	L = number of laboratory/filter combinations
Lower recovery limits for the mean of IPR sample results were then calculated as:

		Where:
	 	Xmean =	the mean recovery of all samples
		t(0.95,df) = 95[th] percentile of the student's t distribution with df degrees of freedom
		df is calculated using Satterthwaite's estimate as given below:

The precision criterion for IPR samples was calculated as a maximum relative standard deviation (RSD). The maximum RSD was determined by first pooling the individual laboratory/round RSDs using the formula below:

	Where:
	RSDi = the RSD calculated for laboratory/filter/round i, and
	C = the number of laboratory/filter/round combinations.
The maximum RSD was then calculated as:

	Where:
	nT = the total number of results from all laboratories over all rounds, and
	C = the number of laboratory/filter/round combinations.

Table 1.  Summary of Acceptance Criteria

                                  Method 1623
                                 2005 version
                  Federal Register 74:36 (February 25, 2009)
                                    p. 8529
                                 Updated Value
OPR Criteria  -  Lower Limit
                             Cryptosporidium - 11%
                                 Giardia - 14%
                             Cryptosporidium - 22%
                            Cryptosporidium  - 33%
                                Giardia  - 29%
IPR Criteria  -  Lower Limit
                            Cryptosporidium  - 24%
                                Giardia -  24%
                                      NA
                            Cryptosporidium  - 36%
                                 Giardia - 32%
IPR Criteria  -  Precision (maximum RSD)
                            Cryptosporidium  - 55%
                                 Giardia - 49%
                                      NA
                            Cryptosporidium  - 34%
                                 Giardia - 37%
Data Set
                     ICRSS data generated in 1999 and 2000
           PT data generated during the February and May 2007 rounds
         PT data generated, as of June 24, 2011, during five PT rounds
Number of Laboratories/Filters
                                       6
                                      58
                             Cryptosporidium - 56
                                 Giardia - 55
Number of Samples
                                      293
                                      333
                             Cryptosporidium - 753
                                 Giardia - 530
Method Version Used
                1999 version of Method 1623  -  Envirochek only
                  2005 version of Method 1623  -  all filters
                  2005 version of Method 1623  -  all filters
Blind vs. Unblind
                                    Unblind
                                     Blind
                                     Blind

                                  Appendix K

                                 Burden Tables


[Federal Register Volume 82, Number 12 (Thursday, January 19, 2017)]
[Notices]
[Pages 6664-6667]
[FR Doc No: 2017-01141]

-----------------------------------------------------------------------

SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-79784; File No. SR-NASDAQ-2016-135]

Self-Regulatory Organizations; The NASDAQ Stock Market LLC;
Notice of Filing of Amendment No. 2 and Order Granting Accelerated
Approval of a Proposed Rule Change, as Modified by Amendment No. 2,
Relating to Continued Listing Requirements for Exchange-Traded Products

January 12, 2017.

I. Introduction

    On September 30, 2016, The NASDAQ Stock Market LLC (``Exchange'' or
``Nasdaq'') filed with the Securities and Exchange Commission
(``Commission''), pursuant to Section 19(b)(1) of the Securities
Exchange Act of 1934 (``Act'') \1\ and Rule 19b-4 thereunder,\2\ a
proposed rule change related to continued listing requirements and
delisting procedures for exchange-traded products listed pursuant to
the Nasdaq Rule 5700 Series. The proposed rule change was published for
comment in the Federal Register on October 17, 2016.\3\ On November 25,
2016, the Commission designated a longer period within which to approve
the proposed rule change, disapprove the proposed rule change, or
institute proceedings to determine whether to approve or disapprove the
proposed rule change.\4\ On January 9, 2017, the Exchange filed
Amendment No. 1 to the proposed rule change. On January 11, 2017, the
Exchange filed Amendment No. 2 to the proposed rule change, which
amended and replaced the original proposal as modified by

Amendment No. 1.\5\ The Commission received no comment letters on the
proposed rule change. The Commission is publishing this notice to
solicit comments on Amendment No. 2 from interested persons, and is
approving the proposed rule change, as modified by Amendment No. 2, on
an accelerated basis.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ See Securities Exchange Act Release No. 79081 (October 11,
2016), 81 FR 71548.
    \4\ See Securities Exchange Act Release No. 79399, 81 FR 86759
(December 1, 2016).
    \5\ In Amendment No. 2, the Exchange: (i) Amended proposed Rule
5701(d) to require a Company with securities listed under the Rule
5700 Series to provide the Exchange with prompt notification if the
Company (rather than an Executive Officer of the Company) becomes
aware of its non-compliance with the requirements of the Rule 5700
Series; (ii) further amended rules within the Rule 5700 Series to
reflect that certain listing requirements (including certain
statements or representations in rule filings for the listing and
trading of specific products) apply on an initial and ongoing basis;
(iii) further amended rules within the Rule 5700 Series to
consistently state that the Exchange will initiate delisting
proceedings if continued listing requirements are not maintained;
(iv) amended the Rule 5700 Series to provide that the Exchange would
initiate delisting proceedings due to an interruption to the
dissemination of index, reference asset, or intraday indicative
values (as applicable to the product) only if the interruption
persists past the trading day in which it occurred; (v) specified an
implementation date for the proposed changes; and (vi) made non-
substantive and conforming changes throughout the Rule 5700 Series
in order to provide consistency throughout these rules, update rule
numbering, and update cross-references. Amendment No. 2 is available
at https://www.sec.gov/comments/sr-nasdaq-2016-135/nasdaq2016135-1481751-130537.pdf.
---------------------------------------------------------------------------

II. Description of the Proposed Rule Change, as Modified by Amendment
No. 2

    The Exchange proposes to amend the Rule 5700 Series to specify
continued listing requirements for products listed under those rules,
which include products listed pursuant to Rule 19b-4(e) under the Act
(``generically-listed products'') and products listed pursuant to
proposed rule changes filed with the Commission (``non-generically-
listed products'').\6\
---------------------------------------------------------------------------

    \6\ See infra notes 13-15 and accompanying text. The Exchange
also proposes to amend certain listing requirements within the Rule
5700 Series. Specifically, the Exchange proposes to amend the
requirement to delist a product if, following the initial 12-month
period following commencement of trading on Nasdaq, there are fewer
than 50 record or beneficial holders of the listed product for 30 or
more consecutive trading days, by deleting the threshold of ``30 or
more consecutive trading days.'' See, e.g., proposed changes to Rule
5705(a)(9)(B)(c).
---------------------------------------------------------------------------

    The Exchange also proposes to amend the Rule 5700 Series to specify
issuer notification requirements related to failures to comply with
continued listing requirements. Specifically, the Exchange proposes to
add Rule 5701(d) to require an issuer with securities listed under the
Rule 5700 Series to promptly notify the Exchange of any non-compliance
with the requirements of the Rule 5700 Series. In addition, with
respect to non-generically-listed products, the Exchange proposes to
require an issuer to notify the Exchange of its failure to comply with
any continued listing requirements that were specified in the proposals
to list those products. As proposed, the Exchange would initiate
delisting proceedings for a product listed under the Rule 5700 Series
if any of its continued listing requirements (including those set forth
in a Nasdaq Rule and those set forth in an applicable proposed rule
change) are not continuously maintained.\7\
---------------------------------------------------------------------------

    \7\ Unlike failures to comply with other continued listing
requirements, if there is an interruption to the dissemination of
the reference asset, index, or intraday indicative values for a
listed product, the Exchange would initiate delisting proceedings
under the Rule 5800 Series only if the interruption persists past
the trading day in which it occurred. See, e.g., proposed changes to
Rules 5705(a)(9)(B)(i)(d)-(e) and 5705(b)(9)(B)(i)(d)-(e).
---------------------------------------------------------------------------

    The Exchange also proposes to amend Rule 5810 to specify the
delisting procedures for products listed under the Rule 5700 Series.
Under proposed Rule 5810(c)(2)(A), unless the issuer is currently under
review by an Adjudicatory Body for a Staff Delisting Determination, the
Listing Qualifications Department may accept and review a plan to
regain compliance when an issuer fails to meet a continued listing
requirement contained in the Rule 5700 Series. The issuer would be
required to submit its compliance plan within 45 calendar days of the
Exchange staff's notification of deficiencies, and certain issuers
would be required to pay a compliance plan review fee.
    Finally, the Exchange proposes to make conforming and technical
changes throughout the Rule 5700 Series to maintain consistency in its
rules. For example, the Exchange proposes to consistently use the
language ``initiate delisting proceedings under the Rule 5800 Series''
when describing the delisting process for a product that fails to meet
continued listing requirements; \8\ consistently state in the Portfolio
Depository Receipts and Index Fund Shares rules that, if the index that
underlies a series of Portfolio Depository Receipts or Index Fund
Shares is maintained by a broker-dealer or fund advisor, the index
shall be calculated by a third party who is not a broker-dealer or fund
advisor; \9\ and consistently reflect that delisting ``following the
initial 12-month period following commencement of trading on Nasdaq''
only applies to the record/beneficial holder, number of shares issued
and outstanding, and the market value of shares issued and outstanding
requirements.\10\
---------------------------------------------------------------------------

    \8\ See, e.g., proposed changes to Rules 5705(a)(9)(B)(i) and
5705(b)(9)(B)(i).
    \9\ See proposed changes to Rules 5705(a)(4)(B)(i),
5705(a)(5)(A)(i), 5705(b)(4)(B)(i), and 5705(b)(5)(A)(i); see also
Rule 5705(a)(3)(B)(i) (currently stating that, for certain Portfolio
Depository Receipts, ``[i]f the index is maintained by a broker-
dealer or fund advisor . . . the index shall be calculated by a
third party who is not a broker-dealer or fund advisor'') and
5705(b)(3)(B)(i) (currently stating that, for certain Index Fund
Shares, ``[i]f the index is maintained by a broker-dealer or fund
advisor . . . the index shall be calculated by a third party who is
not a broker-dealer or fund advisor'').
    \10\ See, e.g., proposed changes to Rule 5711(d)(vi)(B); see
also, e.g., Rule 5711(h)(iv)(B)(1) (currently applying the 12-month
threshold only to the record/beneficial holder, number of units
issued and outstanding, and market value of units issued and
outstanding requirements for Partnership Units).
---------------------------------------------------------------------------

    The Exchange proposes to implement the rule changes by August 1,
2017.

III. Discussion and Commission Findings

    The Commission finds that the proposed rule change, as modified by
Amendment No. 2, is consistent with the requirements of the Act and the
rules and regulations thereunder applicable to a national securities
exchange.\11\ In particular, the Commission finds that the proposed
rule change is consistent with Section 6(b)(5) of the Act,\12\ which
requires, among other things, that the rules of a national securities
exchange be designed to prevent fraudulent and manipulative acts and
practices, to promote just and equitable principles of trade, to remove
impediments to and perfect the mechanism of a free and open market and
a national market system and, in general, to protect investors and the
public interest.
---------------------------------------------------------------------------

    \11\ In approving this proposed rule change, the Commission has
considered the proposed rule's impact on efficiency, competition,
and capital formation. See 15 U.S.C. 78c(f).
    \12\ 15 U.S.C. 78f(b)(5).
---------------------------------------------------------------------------

    The Commission does not believe that the proposal raises unique or
novel regulatory issues. As the Commission previously stated, the
development, implementation, and enforcement of standards governing the
initial and continued listing of securities on an exchange are
activities of critical importance to financial markets and the
investing public. Once a security has been approved for initial
listing, continued listing criteria allow an exchange to monitor the
status and trading characteristics of that issue to ensure that it
continues to meet the exchange's standards for market depth and
liquidity so that fair and orderly markets can be maintained.
    Currently, certain rules within the Rule 5700 Series impose
specific listing requirements on an initial basis, without

imposing ongoing listing requirements that are intended to achieve the
same goals as these initial listing requirements.\13\ To fill this gap,
the proposal would specify that certain listing requirements within the
Rule 5700 Series apply both on an initial and ongoing basis, rather
than only at a single point in time (i.e., at the time of initial
listing).\14\ Also, with respect to non-generically listed products,
the Exchange proposes to amend the Rule 5700 Series to provide that any
of the statements or representations in a proposed rule change
regarding: (i) The description of the index, holdings, or reference
asset (as applicable to a specific product); (ii) limitations on index
composition, holdings, or reference assets (as applicable to a specific
product); (iii) dissemination and availability of index, reference
asset, or intraday indicative values (as applicable to a specific
product); or (iv) the applicability of Exchange rules and surveillance
procedures, constitute continued listing requirements.\15\
---------------------------------------------------------------------------

    \13\ Moreover, certain of the listing requirements do not
explicitly state that they apply on an ongoing, as well as initial,
basis. In these cases, the proposal would make explicit that the
requirements apply both on an initial and ongoing basis. See, e.g.,
proposed changes to Rule 5705(a)(3)(B)-(C) (making explicit that,
for Portfolio Depository Receipts, requirements related to index
methodology and index value dissemination, as well as intraday
indicative value dissemination, apply on an initial and ongoing
basis); proposed changes to Rule 5710(e) (making explicit that, for
Linked Securities, requirements related to tangible net worth and
earnings apply on an initial and ongoing basis); proposed changes to
Rule 5711(c), Commentary .03 (making explicit that, for Trust
Certificates, requirements related to the qualifications of a
trustee and changes to a trustee apply on an initial and ongoing
basis).
    \14\ For example, current Rule 5705(a)(3)(A)(i) sets forth
requirements for component stocks of an index or portfolio
underlying a series of generically-listed Portfolio Depository
Receipts, which apply upon initial listing. These requirements
include, for example, minimum market value, minimum monthly trading
volume, and concentration limits for the component stocks. The
proposal would specify that these requirements apply both on an
initial and continued basis.
    \15\ See, e.g., proposed Rule 5705(a)(9)(B)(i)(b). The
Commission notes that it has approved proposed rule changes for the
listing and trading of exchange-traded products that included
similar representations. See, e.g., Securities Exchange Act Release
No. 77548 (April 6, 2016), 81 FR 21626 (April 12, 2016) (SR-NASDAQ-
2015-161). The Commission also notes that similar types of
requirements exist in the Rule 5700 Series. See, e.g., Rule
5705(a)(3) (setting forth, among other things, index composition
requirements and intraday indicative value dissemination
requirements for certain generically-listed Portfolio Depository
Receipts).
---------------------------------------------------------------------------

    Because the proposal specifies continued listing requirements for
products listed pursuant to the Rule 5700 Series, the Commission
believes the proposal is designed to achieve on a continuing basis the
goals of the listing requirements, including ensuring that the Exchange
lists products that are not susceptible to manipulation and maintaining
fair and orderly markets for the listed products. In particular, the
Commission believes that the proposal is designed to ensure that stocks
with a substantial market capitalization and trading volume account for
a substantial portion of the weight of an index or portfolio underlying
a listed product; \16\ provide transparency regarding the components of
an index or portfolio underlying a listed product; \17\ ensure that
there is adequate liquidity in the listed product itself; \18\ and
provide timely and fair disclosure of useful information that may be
necessary to price the listed product.\19\ Moreover, the Commission
believes that the proposal to require an issuer to notify the Exchange
of its failures to comply with continued listing requirements would
supplement the Exchange's own surveillance of the listed products.\20\
---------------------------------------------------------------------------

    \16\ For example, as proposed, the requirements under Rule
5705(a)(3)(A), including minimum market value and minimum monthly
trading volume requirements for components of the index or portfolio
underlying Portfolio Depository Receipts, would apply both on an
initial and ongoing basis. Also, for non-generically listed
products, the proposal would provide that statements or
representations made in the proposed rule changes relating the
description of the portfolio, among other things, constitute
continued listing requirements. See, e.g., proposed Rule
5705(a)(9)(B)(i)(b).
    \17\ For example, as proposed, the requirements under Rule
5705(a)(3)(A), including the requirement that components of the
index or portfolio underlying Portfolio Depository Receipts be
exchange-listed and NMS stocks, would apply both on an initial and
ongoing basis.
    \18\ For example, the Exchange proposes to amend Rule 5715(b)(2)
to explicitly state that listing requirements for Selected Equity-
Linked Debt Securities (``SEEDS'') apply both on an initial and
ongoing basis, including, for example, the minimum public
distribution and the minimum market value of an issue of SEEDS.
     The Commission also believes that the proposal to delete the
threshold of ``30 or more consecutive trading days'' in the
requirements for the number of beneficial or record holders is
consistent with the goal of ensuring that there is adequate
liquidity in the listed product on an ongoing basis. As proposed,
the Exchange would initiate delisting proceedings for a product if
it fails to comply with the minimum number of beneficial holders
requirement, even if the non-compliance does not continue for 30
consecutive trading days. See supra note 6.
    \19\ For example, the proposed changes to Rule 5705(a)(3)(B)-(C)
would make explicit that the requirements related to the
dissemination of the value of the index underlying Portfolio
Depository Receipts and the Intraday Indicative Value for Portfolio
Depository Receipts apply on an initial and ongoing basis.
    \20\ The Commission notes that this concept of issuer
notification is not novel. For example, in connection with its
proposal to adopt generic listing standards for Managed Fund Shares,
the Exchange stated that, prior to listing pursuant to the generic
listing standards, an issuer would be required to represent to the
Exchange that it will advise the Exchange of any failure by a series
of Managed Fund Shares to comply with the continued listing
requirements, and, pursuant to its obligations under Section
19(g)(1) of the Act, the Exchange will monitor for compliance with
the continued listing requirements. See Securities Exchange Act
Release No. 78918 (September 23, 2016), 81 FR 67033, 67036
(September 29, 2016) (SR-NASDAQ-2016-104).
---------------------------------------------------------------------------

    As noted above, the proposal specifies the delisting procedures for
products listed pursuant to the Rule 5700 Series. The Commission
believes that the proposed amendments to Rule 5810 provide transparency
regarding the process that the Exchange will follow if a listed product
fails to meet its continued listing requirements. The Commission also
notes that the process surrounding compliance plans already exists in
Rule 5810. As a result, the proposed delisting procedures are not
novel.
    Finally, the Commission believes that the conforming and technical
proposed changes do not raise novel issues, are designed to further the
goals of the listing standards, and provide clarity and consistency in
the Exchange's rules.
    For the reasons discussed above, the Commission finds that the
proposed rule change, as modified by Amendment No. 2, is consistent
with the Act.

IV. Accelerated Approval of Amendment No. 2

    As noted above, in Amendment No. 2, the Exchange: (i) Amended
proposed Rule 5701(d) to require a Company with securities listed under
the Rule 5700 Series to provide the Exchange with prompt notification
if the Company (rather than an Executive Officer of the Company)
becomes aware of its non-compliance with the requirements of the Rule
5700 Series; (ii) further amended rules within the Rule 5700 Series to
reflect that certain listing requirements (including certain statements
or representations in rule filings for the listing and trading of
specific products) apply on an initial and ongoing basis; (iii) further
amended rules within the Rule 5700 Series to consistently state that
the Exchange will initiate delisting proceedings if continued listing
requirements are not maintained; (iv) amended rules within the Rule
5700 Series to provide that the Exchange will initiate delisting
proceedings due to an interruption to the dissemination of index,
reference asset, or intraday indicative values (as applicable to the
product) only if the interruption persists past the trading day in
which it occurred; (v) specified an implementation date for the
proposed changes; and (vi) made conforming and non-substantive changes
throughout the

Rule 5700 Series. The Commission believes that Amendment No. 2 furthers
the goals of the proposed rule change and does not raise novel
regulatory issues. Accordingly, the Commission finds good cause,
pursuant to Section 19(b)(2) of the Act,\21\ to approve the proposed
rule change, as modified by Amendment No. 2, on an accelerated basis.
---------------------------------------------------------------------------

    \21\ 15 U.S.C. 78s(b)(2).
---------------------------------------------------------------------------

V. Solicitation of Comments on Amendment No. 2

    Interested persons are invited to submit written data, views, and
arguments concerning the foregoing, including whether Amendment No. 2
is consistent with the Act. Comments may be submitted by any of the
following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to<EMAIL_ADDRESS>Please include
File Number SR-NASDAQ-2016-135 on the subject line.

Paper Comments

     Send paper comments in triplicate to Brent J. Fields,
Secretary, Securities and Exchange Commission, 100 F Street NE.,
Washington, DC 20549-1090.

All submissions should refer to File Number SR-NASDAQ-2016-135. This
file number should be included on the subject line if email is used. To
help the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's Internet Web site (http://www.sec.gov/rules/sro.shtml). Copies of the submission, all subsequent amendments, all
written statements with respect to the proposed rule change that are
filed with the Commission, and all written communications relating to
the proposed rule change between the Commission and any person, other
than those that may be withheld from the public in accordance with the
provisions of 5 U.S.C. 552, will be available for Web site viewing and
printing in the Commission's Public Reference Room, 100 F Street NE.,
Washington, DC 20549, on official business days between the hours of
10:00 a.m. and 3:00 p.m. Copies of the filing also will be available
for inspection and copying at the principal office of the Exchange. All
comments received will be posted without change; the Commission does
not edit personal identifying information from submissions. You should
submit only information that you wish to make available publicly. All
submissions should refer to File Number SR-NASDAQ-2016-135 and should
be submitted on or before February 9, 2017.

VI. Conclusion

    It is therefore ordered, pursuant to Section 19(b)(2) of the
Act,\22\ that the proposed rule change (SR-NASDAQ-2016-135), as
modified by Amendment No. 2, be, and hereby is, approved on an
accelerated basis.
---------------------------------------------------------------------------

    \22\ 15 U.S.C. 78s(b)(2).

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\23\
---------------------------------------------------------------------------

    \23\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Brent J. Fields,
Secretary.
[FR Doc. 2017-01141 Filed 1-18-17; 8:45 am]
 BILLING CODE 8011-01-P


			  UNITED STATES OF AMERICA

		        DEPARTMENT OF TRANSPORTATION

			  OFFICE OF THE SECRETARY

			          WASHINGTON, D.C.

                     Issued by the Department of Transportation on June
28XX, 2005

NOTICE OF ACTION TAKEN -- DOCKET OST-2005-216050878

________________________________________________________________________
________________________________________________________

This serves as notice to the public of the action described below, taken
by the Department official indicated (no additional confirming order
will be issued in this matter).

Applicant: AEROVIAS COMPANIA MEXICANA DE MEXICOAVIACION, S.A. de C.V.
(AeromexicoMexicana)				Date Filed: June 16,April 1, 2005

Leon/Morelia, Mexico, and Chicago, Illinois.Las Vegas, Nevada.

If renewal, date and citation of last action:  New Authority

Applicant representative:  William C. Evans, Charles F. Donley II,
202-861-6459626-6840	     DOT analyst:  Daniel M. Wolfert,
202-366-64502405

Responsive pleadings:  None.

	DISPOSITION

Action:  Approved.
                                          			Action date:  June 28XX,,
2005

(We acted on Aeromexico’s request in less than the full 15-day period
for filing answers with the consent of all parties served)

Effective dates of authority granted:  June 28XX, 2005, through June
28XX, 2006.

Basis for approval (bilateral agreement/reciprocity): United
States-Mexico Air Transport Services Agreement.

Except to the extent exempted/waived, this authority is subject to the
terms, conditions, and limitations of our standard exemption conditions
(attached) and to the otherwise applicable terms, conditions, and
limitations of Mexicana’s foreign air carrier permit (Order
91-5-2578-6-127).

Action taken by:   Paul L. Gretch, Director, Office of International
Aviation

________________________________________________________________________
_______________________

Under authority assigned by the Department in its regulations, 14 CFR
Part 385, we found that (1) our action was consistent with Department
policy; (2) the applicant was qualified to perform its proposed
operations; (3) grant of the authority was consistent with the public
interest; and (4) grant of the authority would not constitute a major
regulatory action under the Energy Policy and Conservation Act of 1975.
To the extent not granted/deferred/dismissed, we denied all requests in
the referenced Docket.  We may amend, modify, or revoke the authority
granted in this Notice at any time without hearing at our discretion.

Persons entitled to petition the Department for review of the action set
forth in this Notice under the Department’s regulations, 14 CFR
§385.30, may file their petitions within seven (7) days after the date
of issuance of this Notice.  This action was effective when taken, and
the filing of a petition for review will not alter such effectiveness.

An electronic version of this document is available on the World Wide
Web at:

  HYPERLINK "http://dms.dot.gov//reports/reports_aviation.asp"
http://dms.dot.gov//reports/reports_aviation.asp

FOREIGN CARRIER EXEMPTION CONDITIONS
                              ATTACHMENT

In the conduct of the operations authorized, the foreign carrier
applicant(s) shall:

1) Not conduct any operations unless it holds a currently effective
authorization from its homeland for such operations, and it has filed a
copy of such authorization with the Department;

2) Comply with all applicable requirements of the Federal Aviation
Administration, including, but not limited to, 14 CFR Parts 129, 91, and
36, and with all applicable U.S. Government requirements concerning
security, including, but not limited to, 49 CFR Part 1546 or 1550, as
applicable.  To assure compliance with all applicable U.S. Government
requirements concerning security, the holder shall, before commencing
any new service (including charter flights) from a foreign airport that
would be the holder’s last point of departure for the United States,
contact its International Principal Security Inspector (IPSI) to advise
the IPSI of its plans and to find out whether the Transportation
Security Administration has determined that security is adequate to
allow such airport(s) to be served;

3) Comply with the requirements for minimum insurance coverage contained
in 14 CFR Part 205, and, prior to the commencement of any operations
under this authority, file evidence of such coverage, in the form of a
completed OST Form 6411, with the Federal Aviation Administration’s
Program Management Branch (AFS-260), Flight Standards Service (any
changes to, or termination of, insurance also shall be filed with that
office);

4) Not operate aircraft under this authority unless it complies with
operational safety requirements at least equivalent to Annex 6 of the
Chicago Convention;

5) Conform to the airworthiness and airman competency requirements of
its Government for international air services;

6) Except as specifically exempted or otherwise provided for in a
Department Order, comply with the requirements of 14 CFR Part 203,
concerning waiver of Warsaw Convention liability limits and defenses;

7) Agree that operations under this authority constitute a waiver of
sovereign immunity, for the purposes of 28 U.S.C. 1605(a), but only with
respect to those actions or proceedings instituted against it in any
court or other tribunal in the United States that are: a) based on its
operations in international air transportation that, according to the
contract of carriage, include a point in the United States as a point of
origin, point of destination, or agreed stopping place, or for which the
contract of carriage was purchased in the United States; or b) based on
a claim under any international agreement or treaty cognizable in any
court or other tribunal of the United States.  In this condition, the
term “international air transportation” means “international
transportation” as defined by the Warsaw Convention, except that all
States shall be considered to be High Contracting Parties for the
purpose of this definition;

8) Except as specifically authorized by the Department, originate or
terminate all flights to/from the United States in its homeland;

9) Comply with the requirements of 14 CFR Part 217, concerning the
reporting of scheduled, nonscheduled, and charter data;

10) If charter operations are authorized, except as otherwise provided
in the applicable aviation agreement, comply with the Department’s
rules governing charters (including 14 CFR Parts 212 and 380); and

11) Comply with such other reasonable terms, conditions, and limitations
required by the public interest as may be prescribed by the Department,
with all applicable orders or regulations of other U.S. agencies and
courts, and with all applicable laws of the United States.

This authority shall not be effective during any period when the holder
is not in compliance with the conditions imposed above.  Moreover, this
authority cannot be sold or otherwise transferred without explicit
Department approval under Title 49 of the U.S. Code.

5/2004

Dan, Charlie did not say in his pleading that these are coterminal
points, meaning that they are interchangeable in the order of flight,
but the “on the one hand” language usually indicates such intent.  I
would double check with George, but I would think that we should mention
that they are coterminals, for specificity’s sake.  Otherwise, I would
add the “on the one hand” language.


[Federal Register Volume 83, Number 186 (Tuesday, September 25, 2018)]
[Notices]
[Pages 48437-48439]
[FR Doc No: 2018-20772]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-0007]

Fee for Using a Tropical Disease Priority Review Voucher in
Fiscal Year 2019

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the fee rates for using a tropical disease priority review
voucher for fiscal year (FY) 2019. The Federal Food, Drug, and Cosmetic
Act (FD&C Act), as amended by the Food and Drug Administration
Amendments Act of 2007 (FDAAA), authorizes FDA to determine and collect
priority review user fees for certain applications for review of drug
or biological products when those applications use a tropical disease
priority review voucher. These vouchers are awarded to the applicants
of certain tropical disease product applications, submitted after
September 27, 2007, upon FDA approval of such applications. The amount
of the fee submitted to FDA with applications using a tropical disease
priority review voucher is determined each fiscal year based on the
difference between the average cost incurred by FDA to review a human
drug application designated as priority review in the previous fiscal
year and the average cost incurred in the review of an application that
is not subject to priority review in the previous fiscal year. This
notice establishes the tropical disease priority review fee rate for FY
2019.

FOR FURTHER INFORMATION CONTACT:
Lola Olajide, Office of Financial Management, Food and Drug
Administration, 8455 Colesville Rd., COLE-14541B, Silver Spring, MD
20993-0002,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    Section 1102 of FDAAA (Pub. L. 110-85) added section 524 to the
FD&C Act (21 U.S.C. 360n). In section 524, Congress encouraged
development of new drug and biological products for prevention and
treatment of tropical diseases by offering additional incentives for
obtaining FDA approval of such products. Under section 524, the
applicant of an eligible human drug application submitted after
September 27, 2007, for a tropical disease (as defined in section
524(a)(3) of the FD&C Act) shall receive a priority review voucher upon
approval of the tropical disease product application (assuming other
criteria are met). The recipient of a tropical disease priority review
voucher may either use the voucher with a future submission to FDA
under section 505(b)(1) of the FD&C Act (21 U.S.C. 355(b)(1)) or
section 351(a) of the Public Health Service Act (42 U.S.C. 262), or
transfer (including by sale) the voucher to another party. The voucher
may be transferred (including by sale) repeatedly until it ultimately
is used for a human drug application submitted to FDA under section
505(b)(1) of the FD&C Act or section 351(a) of the Public Health
Service Act. A priority review is a review conducted with a
Prescription Drug User Fee Act (PDUFA) goal date of 6 months after the
receipt or filing date, depending upon the type of application.
Information regarding the PDUFA goals is available at: https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm511438.pdf.
    The applicant that uses a priority review voucher is entitled to a
priority review but must pay FDA a priority review user fee in addition
to any other fee required by PDUFA. FDA published guidance on its
website about how this tropical disease priority review voucher program
operates (available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080599.pdf).
    This notice establishes the tropical disease priority review fee
rate for FY 2019 as $2,457,140 and outlines FDA's process for
implementing the collection of the priority review user fees. This rate
is effective on October 1, 2018, and will remain in effect through
September 30, 2019, for applications submitted with a tropical disease
priority review voucher. The payment of this priority review user fee
is required in addition to the payment of any other fee that would
normally apply to such an application under PDUFA before FDA will
consider the application complete and acceptable for filing.

II. Tropical Disease Priority Review User Fee for FY 2019

    FDA interprets section 524(c)(2) of the FD&C Act as requiring that
FDA determine the amount of the tropical disease priority review user
fee each fiscal year based on the difference between the average cost
incurred by FDA in the review of a human drug application subject to
priority review in the previous fiscal year and the average cost
incurred by FDA in the review of a human drug application that is not
subject to priority review in the previous fiscal year.
    A priority review is a review conducted with a PDUFA goal date of 6
months after the receipt or filing date, depending on the type of
application. Under the PDUFA goals letter, FDA has committed to
reviewing and acting on 90 percent of the applications granted priority
review status within this expedited timeframe. Normally, an application
for a human drug or biological product will qualify for priority review
if the product is intended to treat a serious condition and, if
approved, would provide a significant improvement in safety or
effectiveness. An application that does not receive a priority
designation receives a standard review. Under the

PDUFA goals letter, FDA committed to reviewing and acting on 90 percent
of standard applications within 10 months of the receipt or filing
date, depending on the type of application. A priority review involves
a more intensive level of effort and a higher level of resources than a
standard review.
    FDA is setting fees for FY 2019, and the previous fiscal year is FY
2018. However, the FY 2018 submission cohort has not been closed out
yet, and the cost data for FY 2018 are not complete. The latest year
for which FDA has complete cost data is FY 2017. Furthermore, because
FDA has never tracked the cost of reviewing applications that get
priority review as a separate cost subset, FDA estimated this cost
based on other data that the Agency has tracked. FDA uses data that the
Agency estimates and publishes on its website each year--standard costs
for review. FDA does not publish a standard cost for ``the review of a
human drug application subject to priority review in the previous
fiscal year.'' However, we expect all such applications would contain
clinical data. The standard cost application categories with clinical
data that FDA does publish each year are: (1) New drug applications
(NDAs) for a new molecular entity (NME) with clinical data and (2)
biologics license applications (BLAs).
    The worksheets for standard costs for FY 2017 show a standard cost
of $5,340,560 for an NME NDA and $4,596,936 for a BLA. Based on these
standard costs, the total cost to review the 57 applications in these
two categories in FY 2017 (31 NME NDAs with clinical data and 26 BLAs)
was $285,077,688. (Note: These numbers exclude the President's
Emergency Plan for AIDS Relief NDAs; no investigational new drug review
costs are included in this amount.) Of these applications 33 (20 NDAs
and 13 BLAs) received priority review, which would mean that the
remaining 24 received standard reviews. Because a priority review
compresses a review that ordinarily takes 10 months into 6 months, FDA
estimates that a multiplier of 1.67 (10 months divided by 6 months)
should be applied to non-priority review costs in estimating the effort
and cost of a priority review as compared to a standard review. This
multiplier is consistent with published research on this subject, which
supports a priority review multiplier in the range of 1.48 to 2.35
(Ref. 1). Using FY 2017 figures, the costs of a priority and standard
review are estimated using the following formula:

(33 [alpha] x 1.67) + (24 [alpha]) = $285,077,688

where ``[alpha]'' is the cost of a standard review and ``[alpha] times
1.67'' is the cost of a priority review. Using this formula, the cost
of a standard review for NME NDAs and BLAs is calculated to be
$3,603,561 (rounded to the nearest dollar) and the cost of a priority
review for NME NDAs and BLAs is 1.67 times that amount, or $6,017,946
(rounded to the nearest dollar). The difference between these two cost
estimates, or $2,414,386, represents the incremental cost of conducting
a priority review rather than a standard review.
    For the FY 2019 fee, FDA will need to adjust the FY 2017
incremental cost by the average amount by which FDA's average costs
increased in the 3 years prior to FY 2018, to adjust the FY 2017 amount
for cost increases in FY 2018. That adjustment, published in the
Federal Register on August 1, 2018 (83 FR 37504), setting FY 2019 PDUFA
fees, is 1.7708 percent for the most recent year, not compounded.
Increasing the FY 2017 incremental priority review cost of $2,414,386
by 1.7708 percent (or 0.017708) results in an estimated cost of
$2,457,140 (rounded to the nearest dollar). This is the tropical
disease priority review user fee amount for FY 2019 that must be
submitted with a priority review voucher for a human drug application
in FY 2019, in addition to any PDUFA fee that is required for such an
application.

III. Fee Schedule for FY 2019

    The fee rate for FY 2019 is set out in table 1:

     Table 1--Tropical Disease Priority Review Schedule for FY 2019
------------------------------------------------------------------------
                                                         Fee rate for FY
                      Fee category                             2019
------------------------------------------------------------------------
Application submitted with a tropical disease priority       $2,457,140
 review voucher in addition to the normal PDUFA fee....
------------------------------------------------------------------------

IV. Implementation of Tropical Disease Priority Review User Fee

    Under section 524(c)(4)(A) of the FD&C Act, the priority review
user fee is due upon submission of a human drug application for which
the priority review voucher is used. Section 524(c)(4)(B) of the FD&C
Act specifies that the application will be considered incomplete if the
priority review user fee and all other applicable user fees are not
paid in accordance with FDA payment procedures. In addition, FDA may
not grant a waiver, exemption, reduction, or refund of any fees due and
payable under section 524 of the FD&C Act (see section 524(c)(4)(C)),
and FDA may not collect priority review voucher fees ``except to the
extent provided in advance in appropriation Acts.'' (Section
524(c)(5)(B) of the FD&C Act.)
    The tropical disease priority review fee established in the new fee
schedule must be paid for any application that is received on or after
October 1, 2018, and submitted with a priority review voucher. This fee
must be paid in addition to any other fee due under PDUFA. Payment
should be made in U.S. currency by electronic check, check, bank draft,
wire transfer, credit card, or U.S. postal money order payable to the
order of the Food and Drug Administration. The preferred payment method
is online using electronic check (Automated Clearing House (ACH) also
known as eCheck). Secure electronic payments can be submitted using the
User Fees Payment Portal at https://userfees.fda.gov/pay. (Note: only
full payments are accepted. No partial payments can be made online).
Once you search for your invoice, select ``Pay Now'' to be redirected
to Pay.gov. Note that electronic payment options are based on the
balance due. Payment by credit card is available for balances that are
less than $25,000. If the balance exceeds this amount, only the ACH
option is available. Payments should be made using U.S bank accounts as
well as U.S. credit cards.
    FDA has partnered with the U.S. Department of the Treasury to use
Pay.gov, a web-based payment application, for online electronic
payment. The Pay.gov feature is available on the FDA website after the
user fee identification (ID) number is generated.
    If paying with a paper check, the user fee ID number should be
included on the check, followed by the words ``Tropical Disease
Priority Review.'' All paper checks should be in U.S. currency from a
U.S. bank made payable and

mailed to: Food and Drug Administration, P.O. Box 979107, St. Louis, MO
63197-9000.
    If checks are sent by a courier that requests a street address, the
courier can deliver the checks to: U.S. Bank, Attention: Government
Lockbox 979107, 1005 Convention Plaza, St. Louis, MO 63101. (Note: This
U.S. Bank address is for courier delivery only.) If you have any
questions concerning courier delivery, contact the U.S. Bank at 314-
418-4013. (This telephone number is only for questions about courier
delivery.) The FDA post office box number (P.O. Box 979107) must be
written on the check. If needed, FDA's tax identification number is 53-
0196965.
    If paying by wire transfer, please reference your unique user fee
ID number when completing your transfer. The originating financial
institution may charge a wire transfer fee. If the financial
institution charges a wire transfer fee, it is required to add that
amount to the payment to ensure that the invoice is paid in full. The
account information is as follows: U.S. Dept. of Treasury, TREAS NYC,
33 Liberty St., New York, NY 10045, Account Number: 75060099, Routing
Number: 021030004, SWIFT: FRNYUS33.

V. Reference

    The following reference is on display with the Dockets Management
Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852, and is available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; it is not
available electronically at https://www.regulations.gov as this
reference is copyright protected. FDA has verified the website address,
as of the date this document publishes in the Federal Register, but
websites are subject to change over time.

1. Ridley, D.B., H.G. Grabowski, and J.L. Moe, ``Developing Drugs
for Developing Countries,'' Health Affairs, vol. 25, no. 2, pp. 313-
324, 2006, available at: https://faculty.fuqua.duke.edu/~willm/
HSM_RA/Documents/HA2006_Ridley_Vouchers.pdf.

    Dated: September 19, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-20772 Filed 9-24-18; 8:45 am]
 BILLING CODE 4164-01-P