2020-15760. New Animal Drugs; Approval of New Animal Drug Applications; Withdrawal of Approval of New Animal Drug Applications; Change of Sponsor

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Final rule; technical amendments.

SUMMARY:

The Food and Drug Administration (FDA or we) is amending the animal drug regulations to reflect application-related actions for new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs) during January, February, and March 2020. FDA is 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 make technical amendments to improve the accuracy of the regulations.

DATES:

This rule is effective July 28, 2020.

FOR FURTHER INFORMATION CONTACT:

George K. Haibel, Center for Veterinary Medicine (HFV-6), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-402-5689, [e-mail].

SUPPLEMENTARY INFORMATION:

I. Approvals

FDA is amending the animal drug regulations to reflect approval actions for NADAs and ANADAs during January, February, and March 2020, 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 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 office of the Dockets Management Staff (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. 240-402-7500. Persons with access to the internet may obtain these documents at the CVM FOIA Electronic Reading Room: https://www.fda.gov/​about-fda/​center-veterinary-medicine/​cvm-foia-electronic-reading-room. Marketing exclusivity and patent information may be accessed in FDA's publication, Approved Animal Drug Products Online (Green Book) at: https://www.fda.gov/​animal-veterinary/​products/​approved-animal-drug-products-green-book.

Table 1—Original and Supplemental NADAs and ANADAs Approved During January, February, and March 2020

Approval date	File No.	Sponsor	Product name	Species	Effect of the action	Public documents
January 28, 2020	141-466	Elanco US Inc., 2500 Innovation Way, Greenfield, IN 46140	Narasin and nicarbazin and avilamycin Type C medicated broiler feeds	Chickens	Supplemental approval of an increased age restriction and reduced withdrawal period in the use of MAXIBAN (narasin and nicarbazin) Type A medicated article) with INTEPRITY (avilamycin) Type A medicated articles in the manufacture of Type C medicated broiler feeds	FOI Summary.
February 7, 2020	200-614	Akorn Animal Health, Inc., 1925 West Field Ct., Suite 300, Lake Forest, IL 60045	Pentobarbital Sodium and Phenytoin Sodium Injectable Solution	Dogs	Original approval as a generic copy of NADA 119-807	FOI Summary.
February 27, 2020	141-521	Zoetis Inc., 333 Portage St., Kalamazoo, MI 49007	SIMPARICA TRIO (sarolaner, moxidectin, and pyrantel chewable tablets) Chewable Tablet	Dogs	Original approval for the prevention of heartworm disease; kills adult fleas and is indicated for the treatment and prevention of flea infestations, the treatment and control of tick infestations, and the treatment and control of roundworm and adult hookworm infections for one month	FOI Summary.
March 10, 2020	200-670	Chanelle Pharmaceuticals Manufacturing Ltd., Loughrea, County Galway, H62 FH90, Ireland	SENERGY (selamectin) Topical Solution	Dogs and cats	Original approval as a generic copy of NADA 141-152	FOI Summary.
March 23, 2020	200-586	Dechra Veterinary Products, LLC, 7015 College Blvd., Suite 525, Overland Park, KS 66211	MARBOQUIN (marbofloxacin) Tablets	Dogs	Original approval as a generic copy of NADA 141-151	FOI Summary.
March 27, 2020	141-322	Zoetis Inc., 333 Portage St., Kalamazoo, MI 49007	IMPROVEST (gonadotropin release factor analog-diphtheria toxoid conjugate) Injectable Solution	Swine	Supplemental approval for the temporary suppression of estrus in gilts intended for slaughter	FOI Summary EA/FONSI.

II. Withdrawals of Approval

Hikma International Pharmaceuticals LLC, P.O. Box 182400, Bayader Wadi Seer, Amman, Jordan 11118 has requested that FDA withdraw approval of ANADA 200-323 for a 1-gram phenylbutazone bolus because the product is no longer manufactured or marketed. Following this withdrawal of approval, Hikma International Pharmaceuticals LLC is no longer the sponsor of an approved application. As provided in the regulatory text of this document, the animal drug regulations are amended to reflect this action. Elsewhere in this issue of the Federal Register , FDA gave notice that approval of ANADA 200-323, and all supplements and amendments thereto, is withdrawn.

III. Changes of Sponsor

Dechra Veterinary Products LLC, 7015 College Blvd., Suite 525, Overland Park, KS 66211 has informed FDA that it has transferred ownership of, and all rights and interest in, approved NADA 008-760 for ADRENOMONE (corticotropin) Injection to Dechra, Ltd., Snaygill Industrial Estate, Keighley Rd., Skipton, North Yorkshire, BD23 2RW, United Kingdom.

Kindred Biosciences, Inc., 1555 Bayshore Hwy., Suite 200, Burlingame, CA 94010 has informed FDA that it has transferred ownership of, and all rights and interest in, approved NADA 141-481 for MIRATAZ (mirtazapine) Transdermal Ointment to Dechra, Ltd., Snaygill Industrial Estate, Keighley Rd., Skipton, North Yorkshire, BD23 2RW, United Kingdom.

Accordingly, we are amending the regulations to reflect these changes.

IV. Technical Amendments

FDA is revising sections for efrotomycin, iodinated casein, maduramicin, mibolerone, nystatin, and poloxalene in 21 CFR part 558 to reflect a tabular format. The section for tiamulin oral dosage forms in 21 CFR part 520 is being revised to correct ownership of certain products. These amendments will improve the readability and accuracy of the animal drug regulations.

V. Legal Authority

This final rule is issued under section 512(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360b(i)), which requires Federal Register publication of “notice[s] . . . effective as a regulation,” of the conditions of use of approved new animal drugs. This rule sets forth technical amendments to the regulations to codify recent actions on approved new animal drug applications and corrections to improve the accuracy of the regulations, and as such does not impose any burden on regulated entities.

Although denominated a rule pursuant to the FD&C Act, this document 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. Likewise, this is not a rule subject to Executive Order 12866, which defines a rule as “an agency statement of general applicability and future effect, which the agency intends to have the force and effect of law, that is designed to implement, interpret, or prescribe law or policy or to describe the procedure or practice requirements of an agency.”

List of Subjects

21 CFR Part 510

• Administrative practice and procedure
• Animal drugs
• Labeling
• Reporting and recordkeeping requirements

21 CFR Parts 520, 522, and 524

• 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, 21 CFR parts 510, 520, 522, 524, and 558 are amended as follows:

PART 510—NEW ANIMAL DRUGS

1. The authority citation for part 510 continues to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.

§ 510.600

[Amended]

2. In § 510.600, in the table in paragraph (c)(1), remove the entry for “Hikma International Pharmaceuticals LLC”; and in the table in paragraph (c)(2), remove the entry for “059115”.

PART 520—ORAL DOSAGE FORM NEW ANIMAL DRUGS

3. The authority citation for part 520 continues to read as follows:

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

§ 520.1310

[Amended]

4. In § 520.1310, in paragraph (b), remove “No. 054771” and in its place add ” Nos. 026637 and 054771”.

§ 520.1720a

[Amended]

5. In § 520.1720a, remove paragraphs (b)(4) and (5) and redesignate paragraph (b)(6) as paragraph (b)(4).

6. Add § 520.2090 to read as follows:

§ 520.2090

Sarolaner, moxidectin, and pyrantel.

(a) Specifications. Each chewable tablet contains:

(1) 3.0 mg sarolaner, 0.06 mg moxidectin, and 12.5 milligrams (mg) pyrantel (as pamoate salt);

(2) 6.0 mg sarolaner, 0.12 mg moxidectin, and 25.0 mg pyrantel (as pamoate salt);

(3) 12.0 mg sarolaner, 0.24 mg moxidectin, and 50.0 mg pyrantel (as pamoate salt);

(4) 24.0 mg sarolaner, 0.48 mg moxidectin, and 100 mg pyrantel (as pamoate salt);

(5) 48.0 mg sarolaner, 0.96 mg moxidectin, and 200 mg pyrantel (as pamoate salt); or

(6) 72.0 mg sarolaner, 1.44 mg moxidectin, and 300 mg pyrantel (as pamoate salt).

(b) Sponsor. See No. 054771 in § 510.600(c) of this chapter.

(c) Conditions of use in dogs—(1) Amount. Administer orally, once a month, at the recommended minimum dose of 0.54 mg/lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

(2) Indications for use. Prevents heartworm disease caused by Dirofilaria immitis, kills adult fleas (Ctenocephalides felis) and is indicated for the treatment and prevention of flea infestations, the treatment and control of tick infestations with Amblyomma americanum (lone star tick), Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick), and Rhipicephalus sanguineus (brown dog tick), and the treatment and control of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and adult hookworm (Ancylostoma caninum and Uncinaria stenocephala) infections for 1 month in dogs and puppies 8 weeks of age and older, and weighing 2.8 pounds or greater.

(3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

§ 520.2455

[Amended]

7. In § 520.2455, in paragraph (b)(2), remove “paragraph (a)(1)” and in its place add “paragraphs (a)(1) and (a)(3)”.

PART 522—IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS

8. The authority citation for part 522 continues to read as follows:

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

§ 522.480

[Amended]

9. In § 522.480, in paragraph (b)(2), remove “026637” and in its place add “043264”.

10. In § 522.1083, revise paragraphs (a) and (c) to read as follows:

§ 522.1083

Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

(a) Specifications. Each milliliter (mL) of solution contains 0.2 milligrams (mg) gonadotropin releasing factor analog-diphtheria toxoid conjugate.

* * * * *

(c) Conditions of use in swine—(1) Amount. Each intact male pig or gilt should receive two 2-mL (0.4 mg) doses by subcutaneous injection. Administer the first dose no earlier than 9 weeks of age. Administer the second dose at least 4 weeks after the first dose.

(2) Indications for use. (i) Intact male pigs intended for slaughter: For the temporary immunological castration (suppression of testicular function) and reduction of boar taint.

(ii) Gilts intended for slaughter: For the temporary suppression of estrus.

(3) Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. For reduction of boar taint, intact male pigs should be slaughtered no earlier than 3 weeks and no later than 10 weeks after the second dose.

§ 522.1697

[Amended]

11. In § 522.1697, in paragraph (b), remove “000061, 051311, and 054925” and in its place add “000061, 051311, 054925, and 059399”.

PART 524—OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS

12. The authority citation for part 524 continues to read as follows:

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

§ 524.1448

[Amended]

13. In § 524.1448, in paragraph (b), remove “086078” and in its place add “043264”.

14. In § 524.1484b, revise the section heading and paragraph (a) to read as follows:

§ 524.1484b

Neomycin, isoflupredone, and tetracaine powder.

(a) Specifications. Each 15-gram insufflator bottle contains 5 milligrams (mg) neomycin sulfate (equivalent to 3.5 mg neomycin base), 1 mg isoflupredone acetate, and 5 mg tetracaine hydrochloride in a powder base.

* * * * *

§ 524.2098

[Amended]

15. In § 524.2098, in paragraph (b), remove “Nos. 054771 and 055529” and in its place add “Nos. 054771, 055529, and 061651”.

PART 558—NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS

16. The authority citation for part 558 continues to read as follows:

Authority: 21 U.S.C. 354, 360b, 360ccc, 360ccc-1, 371.

17. In § 558.68, revise paragraph (e)(1)(iv) to read as follows:

§ 558.68

Avilamycin.

* * * * *

(e) * * *

(1) * * *

Avilamycin in grams/ton	Combination in grams/ton	Indications for use	Limitations	Sponsor
*         *         *         *         *         *         *
(iv) 13.6 to 40.9	Narasin, 27 to 45 plus nicarbazin, 27 to 45	Broiler chickens: For the prevention of mortality caused by necrotic enteritis associated with Clostridium perfringens; and for the prevention of coccidiosis caused by Eimeria necatrix, E. tenella, E. acervulina, E. brunetti, E. mivati, and E. maxima	Feed as the sole ration for 21 consecutive days to chickens that are at risk of developing, but not yet showing clinical signs of, necrotic enteritis associated with Clostridium perfringens. Avilamycin has not been demonstrated to be effective in broiler chickens showing clinical signs of necrotic enteritis prior to the start of medication. To assure responsible antimicrobial drug use in broiler chickens, treatment administration must begin on or before 18 days of age. The safety of avilamycin has not been established in chickens intended for breeding purposes. Do not allow adult turkeys, horses, or other equines access to narasin formulations. Ingestion of narasin by these species has been fatal. Do not feed to chickens producing eggs for human consumption. Narasin and nicarbazin as provided by No. 058198 in § 510.600(c) of this chapter	058198
*         *         *         *         *         *         *

* * * * *

18. In § 558.235, revise paragraph (d) to read as follows:

§ 558.235

Efrotomycin.

* * * * *

(d) Conditions of use in swine—

Efrotomycin in grams/ton	Indications for use	Limitations	Sponsor
(1) 3.6	Swine: For improved feed efficiency	Feed continuously as sole ration. Not to be used in swine weighing more than 250 pounds	000010
(2) 3.6 to 14.5	Swine: For increased rate of weight gain	Feed continuously as sole ration. Not to be used in swine weighing more than 250 pounds	000010

19. Revise § 558.295 to read as follows:

§ 558.295

Iodinated casein.

(a) Type A medicated articles containing grams iodinated casein per pound.

(b) Sponsor. See No. 017762 in § 510.600(c) of this chapter.

(c) Conditions of use— (1) Ducks—

Amount in grams/ton	Indications for use	Limitations	Sponsor
(i) 100 to 200	Growing ducks: For increased rate of weight gain		017762
(ii) [Reserved]

(2) Dairy cows—

Amount in grams/pound	Indications for use	Limitations	Sponsor
(1) 0.5 to 1.5 per 100 lb of body weight	Dairy cows: For increased milk production	This drug is effective for limited periods of time, and the effectiveness is limited to the declining phase of lactation. Administration must be accompanied with increased feed intake. Administration may increase heat sensitivity of the animal	017762
(2) [Reserved]

20. Revise § 558.340 to read as follows:

§ 558.340

Maduramicin.

(a) Specifications. Type A medicated articles containing 4.54 grams maduramicin per pound.

(b) Sponsor. See No. 054771 in § 510.600(c) of this chapter.

(c) Tolerances. See § 556.375 of this chapter.

(d) Conditions of use in chickens—

Amount in grams/ton	Indications for use	Limitations	Sponsor
(1) 4.54 to 5.45	Broiler chickens: For prevention of coccidiosis caused by Eimeria acervulina, E. tenella, E. brunetti, E. maxima, E. necatrix, and E. mivati	Feed continuously as sole ration. For broiler chickens only. Do not feed to laying hens. Withdraw 5 days before slaughter	054771
(2) [Reserved]

21. Revise § 558.348 to read as follows:

§ 558.348

Mibolerone.

(a) Specifications. Each 6.5 ounce can contains 30 or 60 micrograms (µg) of mibolerone.

(b) Sponsor. See No. 054771 in § 510.600(c) of this chapter.

(c) Conditions of use in dogs— (1) Amount. 30 µg for animals weighing up to 25 pounds; 60 µg for animals weighing 26 to 50 pounds; 120 µg for animals weighing 51 to 100 pounds; 180 µg for animals weighing over 100 pounds, or German Shepherds or German Shepherd mix weighing 30 to 80 pounds. Administer daily at least 30 days before expected initiation of heat and continue as long as desired, but for not more than 12 months.

(2) Indications for use. For the prevention of estrus (heat) in adult female dogs not intended primarily for breeding purposes.

(3) Limitations. Mibolerone should not be used in bitches before first estrous period or in purebred Bedlington terriers. It is not intended for animals being used primarily for breeding purposes. Use orally in adult female dogs only. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

22. Revise In § 558.430, revise paragraph (d) to read as follows:

§ 558.430

Nystatin.

* * * * *

(d) Conditions of use—

Amount in grams/ton	Indications for use	Limitations	Sponsor
(1) 50	Growing and laying chickens and growing turkeys: As an aid in the control of crop mycosis and mycotic diarrhea (Candida albicans)		054771
(2) 100	Growing and laying chickens and growing turkeys: For the treatment of crop mycosis and mycotic diarrhea (Candida albicans)	To be fed for 7 to 10 days	054771

23. Revise § 558.465 to read as follows:

§ 558.465

Poloxalene.

(a) Specifications. Dry Type A medicated articles containing 53 percent poloxalene or liquid Type A medicated articles containing 99.5 percent poloxalene.

(b) Sponsor. See No. 066104 in § 510.600(c) of this chapter.

(c) Tolerances. See § 556.517 of this chapter.

(d) Special considerations. Poloxalene dry Type A article and liquid Type A article must be thoroughly blended and evenly distributed in feed prior to use. This may be accomplished by adding the Type A article to a small quantity of feed, mixing thoroughly, then adding this mixture to the remaining feed and again mixing thoroughly.

(e) Conditions of use in cattle—

Poloxalene in grams/ton	Indications for use	Limitations	Sponsor
(1) To deliver 1 to 2 grams per 100 pounds of body weight	Cattle: For prevention of legume (alfalfa, clover) and wheat pasture bloat in cattle	Dosage is 1 gram of poloxalene per 100 pounds of body weight daily and continued during exposure to bloat producing conditions. If bloating conditions are severe, the dose is doubled. Treatment should be started 2 to 3 days before exposure to bloat-producing conditions. Repeat dosage if animals are exposed to bloat-producing conditions more than 12 hours after the last treatment. Do not exceed the higher dosage levels in any 24-hour period	054771
(2) [Reserved]

§ 558. 500

[Amended]

24. In § 558.500, remove reserved paragraphs (e)(1)(iii) and (iv).

Dated: July 15, 2020.

Lauren K. Roth,

Associate Commissioner for Policy.