
[Federal Register Volume 79, Number 173 (Monday, September 8, 2014)]
[Rules and Regulations]
[Pages 53134-53138]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-20325]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 520, 522, and 558

[Docket No. FDA-2014-N-0002]


New Animal Drugs; Buprenorphine; Carprofen; Danofloxacin; 
Follicle Stimulating Hormone; Ractopamine; Salinomycin; Tylosin

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; technical amendment.

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

SUMMARY: The Food and Drug Administration (FDA) is amending the animal 
drug regulations to reflect approval actions for new animal drug 
applications (NADAs) and abbreviated new animal drug applications 
(ANADAs) during July 2014. FDA is also informing the public of the 
availability of summaries of the basis of approval and of environmental 
review documents, where applicable. The animal drug regulations are 
also being amended to add a cross reference to a tolerance.

DATES: This rule is effective September 8, 2014.

FOR FURTHER INFORMATION CONTACT: George K. Haibel, Center for 
Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855, 240-276-9019, 
george.haibel@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: FDA is amending the animal drug regulations 
to reflect approval actions for NADAs and ANADAs during July 2014, as 
listed in table 1. In addition, FDA is informing the public of the 
availability, where applicable, of documentation of environmental 
review required under the National Environmental Policy Act (NEPA) and, 
for actions requiring review of safety or effectiveness data, summaries 
of the basis of approval (FOI Summaries) under the Freedom of 
Information Act (FOIA). These public documents may be seen in the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, between 9 a.m. and 4 
p.m., Monday through Friday. Persons with access to the Internet may 
obtain these documents at the Center for Veterinary Medicine (CVM) FOIA 
Electronic Reading Room: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofFoods/CVM/CVMFOIAElectronicReadingRoom/default.htm. Marketing 
exclusivity and patent information may be accessed in FDA's 
publication, Approved Animal Drug Products Online (Green Book) at: 
http://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/default.htm.
    Also, the animal drug regulations are being amended in 21 CFR 
522.955 to add a cross reference to a tolerance for an inactive vehicle 
in an injectable dosage form product. This amendment is being made to 
improve the accuracy of the regulations.
    This rule does not meet the definition of ``rule'' in 5 U.S.C. 
804(3)(A) because it is a rule of ``particular applicability.'' 
Therefore, it is not subject to the congressional review requirements 
in 5 U.S.C. 801-808.

[[Page 53135]]



                                      Table 1--Original and Supplemental NADAs and ANADAs Approved During July 2014
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                    New animal drug                                21 CFR
       NADA/ANADA                Sponsor              product name              Action            sections        FOIA summary          NEPA  review
--------------------------------------------------------------------------------------------------------------------------------------------------------
013-076 \1\............  Elanco Animal Health,   TYLAN (tylosin         Supplemental approval        520.2640  yes...............  EA/FONSI \2\
                          A Division of Eli       tartrate) Soluble      for the control of
                          Lilly & Co., Lilly      Powder.                mortality caused by
                          Corporate Center,                              necrotic enteritis
                          Indianapolis, IN                               associated with
                          46285.                                         Clostridium
                                                                         perfringens in
                                                                         broiler chickens.
141-207................  Zoetis Inc., 333        ADVOCIN (danofloxacin  Supplemental approval         522.522  yes...............  CE \3\ \4\
                          Portage St.,            injection) Sterile     for control of
                          Kalamazoo, MI 49007.    Injectable Solution.   bovine respiratory
                                                                         disease (BRD) in
                                                                         beef cattle at high
                                                                         risk of developing
                                                                         BRD associated with
                                                                         Mannheimia
                                                                         haemolytica and
                                                                         Pasteurella
                                                                         multocida.
141-431................  Bioniche Animal Health  FOLLTROPIN (porcine    Original approval for        522.1002  yes...............  CE \3\ \5\
                          USA, Inc., 119 Rowe     pituitary-derived      the induction of
                          Rd., Athens, GA 30601.  follicle stimulating   superovulation in
                                                  hormone for            beef and dairy
                                                  injection).            heifers and cows.
141-434................  Abbott Laboratories,    SIMBADOL               Original approval for         522.230  yes...............  CE \3\ \6\
                          North Chicago, IL       (buprenorphine         control of
                          60064.                  injection).            postoperative pain
                                                                         associated with
                                                                         surgical procedures
                                                                         in cats.
200-520................  Norbrook Laboratories,  CARPRIEVE (carprofen)  Original approval as          522.304  yes...............  CE \3\ \7\
                          Ltd., Station Works,    Injection.             a generic copy of
                          Newry BT35 6JP,                                NADA 141-199.
                          Northern Ireland.
200-559................  Zoetis Inc., 333        ACTOGAIN 45            Original approval as          558.500  yes...............  CE \3\ \7\
                          Portage St.,            (ractopamine HCl)      a generic copy of
                          Kalamazoo, MI 49007.    plus RUMENSIN          NADA 141-225.
                                                  (monensin) Type B
                                                  and C medicated
                                                  feeds.
200-566 \1\............  Huvepharma AD, 5th      OPTAFLEXX 45           Original approval as          558.500  yes...............  CE \3\ \7\
                          Floor, 3A Nikolay       (ractopamine HCl)      a generic copy of
                          Haytov Str., 1113       plus RUMENSIN          NADA 141-224.
                          Sophia, Bulgaria.       (monensin) plus
                                                  TYLOVET (tylosin
                                                  phosphate) Type B
                                                  and C medicated
                                                  feeds.
200-567 \1\............  Huvepharma AD, 5th      OPTAFLEXX 45           Original approval as          558.500  yes...............  CE \3\ \7\
                          Floor, 3A Nikolay       (ractopamine HCl)      a generic copy of
                          Haytov Str., 1113       plus RUMENSIN          NADA 141-233.
                          Sophia, Bulgaria.       (monensin) plus
                                                  TYLOVET (tylosin
                                                  phosphate) plus MGA
                                                  (melengestrol
                                                  acetate) Type B and
                                                  C medicated feeds.
200-569 \1\............  Huvepharma AD, 5th      TYLAN (tylosin         Original approval as          558.550  yes...............  CE \3\ \7\
                          Floor, 3A Nikolay       phosphate) plus        a generic copy of
                          Haytov Str., 1113       SACOX (salinomycin     NADA 141-198.
                          Sophia, Bulgaria.       sodium) Type C
                                                  medicated feeds.
200-570 \1\............  Huvepharma AD, 5th      TYLOVET (tylosin       Original approval as          558.550  yes...............  CE \3\ \7\
                          Floor, 3A Nikolay       phosphate) plus BIO-   a generic copy of
                          Haytov Str., 1113       COX (salinomycin       NADA 141-198.
                          Sophia, Bulgaria.       sodium) Type C
                                                  medicated feeds.
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ The listed application is affected by guidance for industry (GFI) 213, ``New Animal Drugs and New Animal Drug Combination Products
  Administered in or on Medicated Feed or Drinking Water of Food-Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning Product
  Use Conditions with GFI 209'', December 2013.
\2\ The Agency has carefully considered an environmental assessment (EA) of the potential environmental impact of this action and has made a finding of
  no significant impact (FONSI).
\3\ The Agency has determined under 21 CFR 25.33 that this action is categorically excluded (CE) from the requirement to submit an environmental
  assessment or an environmental impact statement because it is of a type that does not individually or cumulatively have a significant effect on the
  human environment.
\4\ CE granted under 21 CFR 25.33(d)(5).
\5\ CE granted under 21 CFR 25.33(c).
\6\ CE granted under 21 CFR 25.33(d)(1).
\7\ CE granted under 21 CFR 25.33(a)(1).


[[Page 53136]]

List of Subjects

21 CFR Parts 520 and 522

    Animal drugs.

21 CFR Part 558

    Animal drugs, Animal feeds.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Center for Veterinary Medicine, 21 CFR parts 520, 
522, and 558 are amended as follows:

PART 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS

0
1. The authority citation for 21 CFR part 520 continues to read as 
follows:

    Authority: 21 U.S.C. 360b.


0
2. In Sec.  520.2640, revise paragraphs (b) and (e)(1) to read as 
follows:


Sec.  520.2640  Tylosin.

* * * * *
    (b) Sponsors. (1) No. 000986 for use as in paragraphs (e)(1), 
(e)(2)(i), (e)(2)(ii)(A), (e)(2)(iii), (e)(3), and (e)(4) of this 
section.
    (2) No. 016592 for use as in paragraphs (e)(1)(i)(A), (e)(1)(ii), 
(e)(2)(i), (e)(2)(ii)(A), (e)(2)(iii), (e)(3), and (e)(4) of this 
section.
    (3) No. 061623 for use as in paragraphs (e)(1)(i)(A), (e)(1)(ii), 
(e)(2)(i), (e)(2)(ii)(B), (e)(2)(iii), (e)(3), and (e)(4) of this 
section.
* * * * *
    (e) * * *
    (1) Chickens--(i) Amounts and indications for use.--(A) Administer 
2 grams per gallon (528 parts per million (ppm)) for 1 to 5 days as an 
aid in the treatment of chronic respiratory disease (CRD) associated 
with Mycoplasma gallisepticum in broiler and replacement chickens. For 
the control of CRD associated with M. gallisepticum at time of 
vaccination or other stress in chickens. For the control of CRD 
associated with Mycoplasma synoviae in broiler chickens. Treated 
chickens should consume enough medicated drinking water to provide 50 
milligrams (mg) tylosin per pound of body weight per day.
    (B) Administer 851 to 1,419 mg/gallon (225 to 375 ppm) for 5 days 
for the control of mortality caused by necrotic enteritis associated 
with Clostridium perfringens in broiler chickens.
    (ii) Limitations. Do not use in layers producing eggs for human 
consumption. Do not administer within 24 hours of slaughter.
* * * * *

PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS

0
3. The authority citation for 21 CFR part 522 continues to read as 
follows:

    Authority: 21 U.S.C. 360b.


0
4. Add Sec.  522.230 to read as follows:


Sec.  522.230  Buprenorphine.

    (a) Specifications. Each milliliter of solution contains 1.8 
milligrams (mg) buprenorphine.
    (b) Sponsor. See No. 000044 in Sec.  510.600(c) of this chapter.
    (c) Conditions of use in cats--(1) Amount. Administer 0.24 mg per 
kilogram (0.11 mg per pound) by subcutaneous injection once daily, for 
up to 3 days. Administer the first dose approximately 1 hour prior to 
surgery.
    (2) Indications for use. For the control of postoperative pain 
associated with surgical procedures in cats.
    (3) Limitations. Federal law restricts this drug to use by or on 
the order of a licensed veterinarian.


Sec.  522.304  [Amended]

0
5. In Sec.  522.304, paragraph (b), remove ``No. 054771'' and in its 
place add ``Nos. 054771 and 055529''.

0
6. In Sec.  522.522, remove paragraph (d)(2); redesignate paragraph 
(d)(3) as paragraph (d)(2); and revise paragraph (d)(1) to read as 
follows:


Sec.  522.522  Danofloxacin.

* * * * *
    (d) * * *
    (1) Amount and indications for use. Administer by subcutaneous 
injection either:
    (i) 6 mg per kilogram (/kg) of body weight, repeated in 48 hours, 
for the treatment of bovine respiratory disease (BRD) associated with 
Mannheimia haemolytica and Pasteurella multocida; or
    (ii) 8 mg/kg of body weight as a single dose for the treatment of 
BRD associated with M. haemolytica and P. multocida and for the control 
of BRD in beef cattle at high risk of developing BRD associated with M. 
haemolytica and P. multocida.
* * * * *

0
7. In Sec.  522.955, revise paragraph (c) to read as follows:


Sec.  522.955  Florfenicol.

* * * * *
    (c) Related tolerances. See Sec. Sec.  500.1410 and 556.283 of this 
chapter.
* * * * *

0
8. In Sec.  522.1002, add paragraph (c) to read as follows:


Sec.  522.1002  Follicle stimulating hormone.

* * * * *
    (c)(1) Specifications. Each package contains 2 vials. One vial 
contains 700 international units (IU) porcine-pituitary derived 
follicle stimulating hormone (FSH) equivalent to 400 milligrams NIH-
FSH-P1, as a dry powder. The other vial contains 20 milliliters (mL) of 
bacteriostatic sodium chloride injection. When reconstituted, each 
milliliter of constituted solution contains 35 IU FSH.
    (2) Sponsor. See No. 064847 in Sec.  510.600(c) of this chapter.
    (3) Conditions of use--(i) Dosage. Administer 2.5 mL (87.5 IU) 
intramuscularly, twice daily at 12-hour intervals, for 4 consecutive 
days. In conjunction with the 6th dose, administer an approved 
prostaglandin product for cattle (cloprostenol sodium or dinoprost 
tromethamine), using the labeled dosage and administration instructions 
to cause luteolysis and induce estrus. See Sec.  522.460 for use of 
cloprostenol sodium or Sec.  522.690 for use of dinoprost tromethamine.
    (ii) Indications for use. For the induction of superovulation in 
beef and dairy heifers and cows.
    (iii) Limitations. Federal law restricts this drug to use by or on 
the order of a licensed veterinarian.

PART 558--NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS

0
9. The authority citation for 21 CFR part 558 continues to read as 
follows:

    Authority: 21 U.S.C. 360b, 371.


0
10. In Sec.  558.500, revise paragraphs (e)(2)(ii), (e)(2)(iv), 
(e)(2)(vii), (e)(2)(ix), (e)(2)(x), (e)(2)(xii), and (e)(2)(xiii), to 
read as follows:


Sec.  558.500  Ractopamine.

* * * * *
    (e) * * *
    (2) * * *

[[Page 53137]]



----------------------------------------------------------------------------------------------------------------
                                   Combination in    Indications for
    Ractopamine in grams/ton         grams/ton             use            Limitations             Sponsor
----------------------------------------------------------------------------------------------------------------
 
                                                  * * * * * * *
(ii) 8.2 to 24.6...............  Monensin 10 to 40  Cattle fed in      As in paragraph    000986, 054771
                                  to provide 0.14    confinement for    (e)(2)(i) of
                                  to 0.42 mg         slaughter: As in   this section;
                                  monensin/lb of     paragraph          see paragraph
                                  body weight,       (e)(2)(i) of       Sec.  Sec.
                                  depending on       this section;      558.355(d) of
                                  severity of        for prevention     this chapter.
                                  coccidiosis        and control of     Ractopamine as
                                  challenge, up to   coccidiosis due    provided by Nos.
                                  480 mg/head/day.   to Eimeria bovis   000986 or 054771
                                                     and E zuernii.     in Sec.
                                                                        510.600(c) of
                                                                        this chapter;
                                                                        monensin as
                                                                        provided by No.
                                                                        000986 in Sec.
                                                                        510.600(c) of
                                                                        this chapter.
 
                                                  * * * * * * *
(iv) 8.2 to 24.6...............  Monensin 10 to 40  Cattle fed in      As in paragraph    000986, 016592, 054771
                                  to provide 0.14    confinement for    (e)(2)(i) of
                                  to 0.42 mg         slaughter: As in   this section;
                                  monensin/lb of     paragraph          see Sec.  Sec.
                                  body weight,       (e)(2)(i) of       558.355(d) and
                                  depending on       this section;      558.625(c) of
                                  severity of        for prevention     this chapter.
                                  coccidiosis        and control of     Ractopamine as
                                  challenge, up to   coccidiosis due    provided by No.
                                  480 mg/head/day,   to Eimeria bovis   000986 with
                                  plus tylosin 8     and E zuernii;     tylosin as
                                  to 10.             and for            provided by Nos.
                                                     reduction of       000986 or 016592
                                                     incidence of       in Sec.
                                                     liver abscesses    510.600(c) of
                                                     caused by          this chapter; or
                                                     Fusobacterium      ractopamine as
                                                     necrophorum and    provided by No.
                                                     Arcanobacterium    054771 with
                                                     (Actinomyces)      tylosin as
                                                     pyogenes.          provided by No.
                                                                        000986 in Sec.
                                                                        510.600(c) of
                                                                        this chapter.
 
                                                  * * * * * * *
(vii) 9.8 to 24.6..............  Monensin 10 to 40  Cattle fed in      As in paragraph    000986, 054771
                                  to provide 0.14    confinement for    (e)(2)(vi) of
                                  to 0.42 mg         slaughter: As in   this section;
                                  monensin/lb of     paragraph          see paragraph
                                  body weight,       (e)(2)(vi) of      Sec.  Sec.
                                  depending on       this section;      558.355(d) of
                                  severity of        for prevention     this chapter.
                                  coccidiosis        and control of     Ractopamine as
                                  challenge, up to   coccidiosis due    provided by Nos.
                                  480 mg/head/day.   to Eimeria bovis   000986 or 054771
                                                     and E zuernii.     in Sec.
                                                                        510.600(c) of
                                                                        this chapter;
                                                                        monensin as
                                                                        provided by No.
                                                                        000986 in Sec.
                                                                        510.600(c) of
                                                                        this chapter.
 
                                                  * * * * * * *
(ix) 9.8 to 24.6...............  Monensin 10 to 40  Cattle fed in      As in paragraph    000986, 016592, 054771
                                  to provide 0.14    confinement for    (e)(2)(vi) of
                                  to 0.42 mg         slaughter: As in   this section;
                                  monensin/lb of     paragraph          see Sec.  Sec.
                                  body weight,       (e)(2)(vi) of      558.355(d) and
                                  depending on       this section;      558.625(c) of
                                  severity of        for prevention     this chapter.
                                  coccidiosis        and control of     Ractopamine and
                                  challenge, up to   coccidiosis due    monensin as
                                  480 mg/head/day,   to Eimeria bovis   provided by No.
                                  plus tylosin 8     and E zuernii;     000986 with
                                  to 10.             and for            tylosin as
                                                     reduction of       provided by Nos.
                                                     incidence of       000986 or 016592
                                                     liver abscesses    in Sec.
                                                     caused by          510.600(c) of
                                                     Fusobacterium      this chapter; or
                                                     necrophorum and    ractopamine as
                                                     Arcanobacterium    provided by No.
                                                     (Actinomyces)      054771 with
                                                     pyogenes.          monensin and
                                                                        tylosin as
                                                                        provided by No.
                                                                        000986 in Sec.
                                                                        510.600(c) of
                                                                        this chapter.

[[Page 53138]]

 
(x) 9.8 to 24.6................  Monensin 10 to 40  Heifers fed in     As in paragraph    000986, 016592, 054771
                                  to provide 0.14    confinement for    (e)(2)(vi) of
                                  to 0.42 mg         slaughter: As in   this section;
                                  monensin/lb of     paragraph          see paragraphs
                                  body weight,       (e)(2)(vi) of      Sec.  Sec.
                                  depending on       this section;      558.342(d),
                                  severity of        for prevention     558.355(d) and
                                  coccidiosis        and control of     558.625(c) of
                                  challenge, up to   coccidiosis due    this chapter.
                                  480 mg/head/day,   to Eimeria bovis   Ractopamine,
                                  plus tylosin 8     and E zuernii;     monensin, and
                                  to 10, plus        for reduction of   tylosin as
                                  melengestrol       incidence of       provided by No.
                                  acetate to         liver abscesses    000986 with
                                  provide 0.25 to    caused by          melengestrol
                                  0.5 mg/head/day.   Fusobacterium      acetate as
                                                     necrophorum and    provided by Nos.
                                                     Arcanobacterium    000986 or 054771
                                                     (Actinomyces)      in Sec.
                                                     pyogenes; and      510.600(c) of
                                                     for suppression    this chapter; or
                                                     of estrus (heat).  ractopamine and
                                                                        monensin as
                                                                        provided by No.
                                                                        000986 with
                                                                        tylosin as
                                                                        provided by Nos.
                                                                        000986 or 016592
                                                                        and melengestrol
                                                                        acetate as
                                                                        provided by No.
                                                                        054771 in Sec.
                                                                        510.600(c) of
                                                                        this chapter; or
                                                                        ractopamine as
                                                                        provided by No.
                                                                        054771 with
                                                                        monensin and
                                                                        tylosin as
                                                                        provided by No.
                                                                        000986 and
                                                                        melengestrol
                                                                        acetate provided
                                                                        by No. 054771 in
                                                                        Sec.
                                                                        510.600(c) of
                                                                        this chapter.
 
                                                  * * * * * * *
(xii) Not to exceed 800; to      Monensin 10 to 40  Cattle fed in      Top dress          000986, 054771
 provide 70 to 400 mg/head/day.   to provide 0.14    confinement for    ractopamine in a
                                  to 0.42 mg         slaughter: As in   minimum of 1.0
                                  monensin/lb of     paragraph          lb of medicated
                                  body weight,       (e)(2)(i) of       feed during the
                                  depending on       this section;      last 28 to 42
                                  severity of        for prevention     days on feed.
                                  coccidiosis        and control of     Not for animals
                                  challenge, up to   coccidiosis due    intended for
                                  480 mg/head/day.   to Eimeria bovis   breeding. See
                                                     and E zuernii.     Sec.
                                                                        558.355(d).
                                                                        Ractopamine as
                                                                        provided by Nos.
                                                                        000986 or 054771
                                                                        in Sec.
                                                                        510.600(c) of
                                                                        this chapter;
                                                                        monensin as
                                                                        provided by No.
                                                                        000986 in Sec.
                                                                        510.600(c) of
                                                                        this chapter.
(xiii) Not to exceed 800; to     Monensin 10 to 40  Cattle fed in      Top dress          000986, 016592, 054771
 provide 70 to 400 mg/head/day.   to provide 0.14    confinement for    ractopamine in a
                                  to 0.42 mg         slaughter: As in   minimum of 1.0
                                  monensin/lb of     paragraph          lb of medicated
                                  body weight,       (e)(2)(i) of       feed during the
                                  depending on       this section;      last 28 to 42
                                  severity of        for prevention     days on feed.
                                  coccidiosis        and control of     Not for animals
                                  challenge, up to   coccidiosis due    intended for
                                  480 mg/head/day,   to Eimeria bovis   breeding. See
                                  plus tylosin 8     and E zuernii;     Sec.  Sec.
                                  to 10.             and for            558.355(d) and
                                                     reduction of       558.625(c).
                                                     incidence of       Ractopamine and
                                                     liver abscesses    monensin as
                                                     caused by          provided by No.
                                                     Fusobacterium      000986 with
                                                     necrophorum and    tylosin as
                                                     Arcanobacterium    provided by Nos.
                                                     (Actinomyces)      000986 or 016592
                                                     pyogenes.          in Sec.
                                                                        510.600(c) of
                                                                        this chapter; or
                                                                        ractopamine as
                                                                        provided by No.
                                                                        054771 with
                                                                        monensin and
                                                                        tylosin as
                                                                        provided by No.
                                                                        000986 in Sec.
                                                                        510.600(c) of
                                                                        this chapter.
----------------------------------------------------------------------------------------------------------------

* * * * *

0
11. In Sec.  558.550, revise the last sentence in paragraph 
(d)(1)(xxii)(B) to read as follows:


Sec.  558.550  Salinomycin.

* * * * *
    (d) * * *
    (1) * * *
    (xxii) * * *
    (B) * * * Salinomycin as provided by Nos. 016592 and 054771; 
tylosin phosphate as provided by Nos. 000986 and 016592 in Sec.  
510.600(c) of this chapter.
* * * * *

    Dated: August 21, 2014.
Bernadette Dunham,
Director, Center for Veterinary Medicine.
[FR Doc. 2014-20325 Filed 9-5-14; 8:45 am]
BILLING CODE 4164-01-P


