26690 Federal Register / Vol. 63, No. 92 /Wednesday, May 13, 1998 / Proposed Rules

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 3, 5, 10, 16, 25, 50, 56,

58, 71, 200, 201, 207, 210, 211, 310, 312,

314, 369, 429, 800, and 812

[Docket No. 98N–0210]

Removal of Regulations Regarding

Certification of Drugs Composed

Wholly or Partly of Insulin; Companion

Document to Direct Final Rule

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule.

SUMMARY: The Food and Drug

Administration (FDA) is publishing this

companion proposed rule to the direct

final rule, published elsewhere in this

issue of the Federal Register, which is

intended to repeal FDA’s regulations

governing certification of drugs

containing insulin and make

conforming amendments to other

sections of the agency’s regulations. The

agency is taking this action in

accordance with provisions of the Food

and Drug Administration Modernization

Act of 1997 (FDAMA). FDAMA repealed

the statutory provision in the Federal

Food, Drug, and Cosmetic Act (the act)

under which the agency certified drugs

containing insulin. FDAMA also made

conforming amendments to the act.

DATES: Comments must be received on

or before July 27, 1998.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Wayne H. Mitchell, Center for Drug

Evaluation and Research (HFD–7), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–594–

2041.

SUPPLEMENTARY INFORMATION:

I. Background

Section 125(a) of FDAMA (Pub. L.

105–115) repealed section 506 of the act

(21 U.S.C. 356) and made other

conforming amendments to the act and

another provision of Federal law.

Section 506 was the statutory provision

in the act under which the agency

certified drugs containing insulin. FDA

is proposing to remove all regulations

relating to the certification of insulin

products, remove citations to section

506 of the act in various authority

sections in title 21 of the Code of

Federal Regulations (CFR), and

eliminate citations to section 506 in

regulations that do not deal primarily

with the certification of insulin. FDA is

also proposing to eliminate out-of-date

provisions dealing with labeling and

testing of insulin and to update the

definition of insulin found in 21 CFR

200.15.

II. Additional Information

This proposed rule is a companion to

the direct final rule published elsewhere

in this issue of the Federal Register. The

companion proposed rule and the direct

final rule are identical. This companion

proposed rule will provide the

procedural framework to finalize the

rule in the event the direct final rule

receives significant adverse comment

and is withdrawn. The comment period

for the companion proposed rule runs

concurrently with the comment period

of the direct final rule. Any comments

received under the companion proposed

rule will be treated as comments

regarding the direct final rule.

Most of the amendments in this rule

are a direct result of the repeal of the

statutory certification provision. The

remainder of the amendments repeal or

update out-of-date, noncontroversial

regulations dealing with insulin. If no

significant adverse comment is received

in response to the direct final rule, no

further action will be taken related to

the companion proposed rule. Instead,

FDA will publish a confirmation

document within 30 days after the

comment period ends confirming that

the direct final rule will go into effect

on September 25, 1998. If FDA receives

significant adverse comments, the

agency will withdraw the direct final

rule. FDA will proceed to respond to all

of the comments received regarding the

rule and, if appropriate, the rule will be

finalized under this companion

proposed rule using usual notice-andcomment procedures.

For additional information, see the

corresponding direct final rule

published elsewhere in this issue of the

Federal Register. All persons who wish

to comment should review the detailed

rationale for these amendments set out

in the preamble discussion of the direct

final rule. A significant adverse

comment is one that explains why the

rule would be inappropriate, including

challenges to the rule’s underlying

premise or approach, or would be

ineffective or unacceptable without a

change. A comment recommending a

rule change in addition to this rule will

not be considered a significant adverse

comment, unless the comment states

why this rule would be ineffective

without the additional change.

III. Environmental Impact

The agency has determined under 21

CFR 25.30(h) that this action is of a type

that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment

nor an environmental impact statement

is required.

IV. Analysis of Impacts

FDA has examined the impacts of this

companion proposed rule under

Executive Order 12866, the Regulatory

Flexibility Act (5 U.S.C. 601–612), and

the Unfunded Mandates Reform Act of

1995 (Pub. L. 104–4). Executive Order

12866 directs agencies to assess all costs

and benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts; and equity). Executive Order

12866 classifies a rule as significant if

it meets any one of a number of

specified conditions, including having

an annual effect on the economy of $100

million or adversely affecting in a

material way a sector of the economy,

competition, or jobs, or if it raises novel

legal or policy issues. The agency

believes that this proposed rule is

consistent with the regulatory

philosophy and principles identified in

the Executive Order. In addition, the

proposed rule is not a significant

regulatory action as defined by the

Executive Order and so is not subject to

review under the Executive Order.

The Regulatory Flexibility Act

requires agencies to analyze regulatory

options to minimize any significant

impact on small entities. The only two

current manufacturers marketing insulin

drug products in the United States are

not small entities. Furthermore, by

eliminating the certification process,

this direct final rule would lower

market entry barriers for small entities.

The agency certifies that the proposed

rule will not have a significant impact

on a substantial number of small

entities. Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

The Unfunded Mandates Act requires

an agency to prepare a budgetary impact

statement before issuing any rule likely

to result in a Federal mandate that may

result in expenditures by State, local,

and tribal governments or the private

sector of $100 million (adjusted

annually for inflation) in any 1 year.

The elimination of the insulin

certification program will lower the
Federal Register / Vol. 63, No. 92 /Wednesday, May 13, 1998 / Proposed Rules 26691

costs of marketing insulin drug products

by eliminating both the direct cost of

applying for certification and the cost of

holding batches of insulin while

awaiting certification. Because this rule

will not result in an expenditure of $100

million or more on any governmental

entity or the private sector, no budgetary

impact statement is required.

V. Paperwork Reduction Act of 1995

FDA tentatively concludes that this

proposed rule contains no collections of

information. Therefore, clearance by the

Office of Management and Budget under

the Paperwork Reduction Act of 1995

(Pub. L. 104–13) is not required.

VI. Request for Comments

Interested persons may, on or before

September 27, 1998, submit to the

Dockets Management Branch (address

above) written comments regarding this

proposal. This comment period runs

concurrently with the comment period

for the direct final rule; any comments

received will be considered as

comments regarding the direct final

rule. Two copies of any comments are

to be submitted, except that individuals

may submit one copy. Comments are to

be identified with the docket number

found in brackets in the heading of this

document. Received comments may be

seen in the office above between 9 a.m.

and 4 p.m., Monday through Friday.

List of Subjects

21 CFR Part 3

Administrative practice and

procedure, Biologics, Drugs, Medical

devices.

21 CFR Part 5

Authority delegations (Government

agencies), Imports, Organization and

functions (Government agencies).

21 CFR Part 10

Administrative practice and

procedure, News media.

21 CFR Part 16

Administrative practice and

procedure.

21 CFR Part 25

Environmental impact statements,

Foreign relations, Reporting and

recordkeeping requirements.

21 CFR Part 50

Human research subjects, Prisoners,

Reporting and recordkeeping

requirements, Safety.

21 CFR Part 56

Human research subjects, Reporting

and recordkeeping requirements, Safety.

21 CFR Part 58

Laboratories, Reporting and

recordkeeping requirements.

21 CFR Part 71

Administrative practice and

procedure, Color additives, Confidential

business information, Cosmetics, Drugs,

Reporting and recordkeeping

requirements.

21 CFR Part 200

Drugs, Prescription drugs.

21 CFR Part 201

Drugs, Labeling, Reporting and

recordkeeping requirements.

21 CFR 207

Drugs, Reporting and recordkeeping

requirements.

21 CFR 210

Drugs, Packaging and containers.

21 CFR Part 211

Drugs, Labeling, Laboratories,

Packaging and containers, Prescription

drugs, Reporting and recordkeeping

requirements, Warehouses.

21 CFR Part 310

Administrative practice and

procedure, Drugs, Labeling, Medical

devices, Reporting and recordkeeping

requirements.

21 CFR Part 312

Drugs, Exports, Imports,

Investigations, Labeling, Medical

research, Reporting and recordkeeping

requirements, Safety.

21 CFR Part 314

Administrative practice and

procedure, Confidential business

information, Drugs, Reporting and

recordkeeping requirements.

21 CFR Part 369

Labeling, Medical devices, Over-thecounter drugs.

21 CFR Part 429

Administrative practice and

procedure, Drugs, Labeling, Packaging

and containers, Reporting and

recordkeeping requirements.

21 CFR Part 800

Administrative practice and

procedure, Medical devices,

Ophthalmic goods and services,

Packaging and containers, Reporting

and recordkeeping requirements.

21 CFR Part 812

Health records, Medical devices,

Medical research, Reporting and

recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, it is proposed that

21 CFR parts 3, 5, 10, 16, 25, 50, 56, 58,

71, 200, 201, 207, 210, 211, 310, 312,

314, 369, 429, 800, and 812 be amended

as follows:

PART 3—PRODUCT JURISDICTION

1. The authority citation for 21 CFR

part 3 is revised to read as follows:

Authority: 21 U.S.C. 321, 351, 352, 353,

355, 357, 360, 360c–360f, 360h–360j, 360gg–

360ss, 371(a), 379e, 381, 394; 42 U.S.C. 216,

262.

PART 5—DELEGATIONS OF

AUTHORITY AND ORGANIZATION

2. The authority citation for 21 CFR

part 5 continues to read as follows:

Authority: 5 U.S.C. 504, 552, App. 2; 7

U.S.C. 138a, 2271; 15 U.S.C. 638, 1261–1282,

3701–3711a; 15 U.S.C. 1451–1461; 21 U.S.C.

41–50, 61–63, 141–149, 321–394, 467f,

679(b), 801–886, 1031–1309; 35 U.S.C. 156;

42 U.S.C. 241, 242, 242a, 242l, 242n, 243,

262, 263, 264, 265, 300u–300u–5, 300aa–1;

1395y, 3246b, 4332, 4831(a), 10007–10008;

E.O. 11921, 41 FR 24294, 3 CFR, 1977 Comp.,

p. 124–131; E.O. 12591, 52 FR 13414, 3 CFR,

1988 Comp., p. 220–223.

§ 5.31 [Amended]

3. Section 5.31 Petitions under part 10

is amended by removing and reserving

paragraphs (f)(2)(iii) and (f)(2)(iv).

§ 5.73 [Removed]

4. Section 5.73 Certification of insulin

is removed.

§ 5.74 [Removed]

5. Section 5.74 Issuance, amendment,

or repeal of regulations pertaining to

drugs containing insulin is removed.

PART 10—ADMINISTRATIVE

PRACTICES AND PROCEDURES

6. The authority citation for 21 CFR

part 10 continues to read as follows:

Authority: 21 U.S.C. 41–50, 141–149, 321–

394, 467f, 679, 821, 1034; 42 U.S.C. 201, 262,

263b, 264; 15 U.S.C. 1451–1461; 5 U.S.C.

551–558, 701–721; 28 U.S.C. 2112.

§ 10.50 [Amended]

7. Section 10.50 Promulgation of

regulations and orders after an

opportunity for a formal evidentiary

public hearing is amended by removing

and reserving paragraph (c)(10).

PART 16—REGULATORY HEARING

BEFORE THE FOOD AND DRUG

ADMINISTRATION

8. The authority citation for 21 CFR

part 16 continues to read as follows:
26692 Federal Register / Vol. 63, No. 92 /Wednesday, May 13, 1998 / Proposed Rules

Authority: 21 U.S.C. 41–50, 141–149, 321–

394, 467f, 679, 821, 1034; 42 U.S.C. 201, 262,

264; 15 U.S.C. 1451–1461; 28 U.S.C. 2112.

§ 16.1 [Amended]

9. Section 16.1 Scope is amended in

paragraph (b)(2) by removing the entry

for ‘‘§ 429.50.’’

PART 25—ENVIRONMENTAL IMPACT

CONSIDERATIONS

10. The authority citation for 21 CFR

part 25 continues to read as follows:

Authority: 21 U.S.C. 321–393; 42 U.S.C.

262, 263b–264; 42 U.S.C. 4321, 4332; 40 CFR

parts 1500–1508; E.O. 11514, 35 FR 4247, 3

CFR, 1971 Comp., p. 531–533 as amended by

E.O. 11991, 42 FR 26967, 3 CFR, 1978 Comp.,

p. 123–124 and E.O. 12114, 44 FR 1957, 3

CFR, 1980 Comp., p. 356–360.

§ 25.31 [Amended]

11. Section 25.31 Human drugs and

biologics is amended in paragraph (f) by

removing the words ‘‘or insulin.’’

PART 50—PROTECTION OF HUMAN

SUBJECTS

12. The authority citation for 21 CFR

part 50 is revised to read as follows:

Authority: 21 U.S.C. 321, 346, 346a, 348,

352, 353, 355, 357, 360, 360c–360f, 360h–

360j, 371, 379e, 381; 42 U.S.C. 216, 241, 262,

263b–263n.

§ 50.1 [Amended]

13. Section 50.1 Scope is amended in

the last sentence of paragraph (a) by

removing the number ‘‘506,’’.

PART 56—INSTITUTIONAL REVIEW

BOARDS

14. The authority citation for 21 CFR

part 56 is revised to read as follows:

Authority: 21 U.S.C. 321, 346, 346a, 348,

351, 352, 353, 355, 357, 360, 360c–360f,

360h–360j, 371, 379e, 381; 42 U.S.C. 216,

241, 262, 263b–263n.

PART 58—GOOD LABORATORY

PRACTICE FOR NONCLINICAL

LABORATORY STUDIES

15. The authority citation for 21 CFR

part 58 is revised to read as follows:

Authority: 21 U.S.C. 342, 346, 346a, 348,

351, 352, 353, 355, 357, 360, 360b–360f,

360h–360j, 371, 379e, 381; 42 U.S.C. 216,

262, 263b–263n.

PART 71—COLOR ADDITIVE

PETITIONS

16. The authority citation for 21 CFR

part 71 is revised to read as follows:

Authority: 21 U.S.C. 321, 342, 348, 351,

355, 357, 360, 360b–360f, 360h–360j, 361,

371, 379e, 381; 42 U.S.C. 216, 262.

PART 200—GENERAL

17. The authority citation for 21 CFR

part 200 is revised to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352,

353, 355, 357, 358, 360e, 371, 374, 375.

18. Section 200.15 is revised to read

as follows:

§ 200.15 Definition of term ‘‘insulin.’’

For purposes of sections 801 and 802

of the act and this title, the term insulin

means the active principle of the

pancreas that affects the metabolism of

carbohydrates in the animal body and

which is of value in the treatment of

diabetes mellitus. The term includes

synthetic and biotechnologically

derived products that are the same as,

or similar to, naturally occurring

insulins in structure, use, and intended

effect and are of value in the treatment

of diabetes mellitus.

PART 201—LABELING

19. The authority citation for 21 CFR

part 201 is revised to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352,

353, 355, 357, 358, 360, 360b, 360gg–360ss,

371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.

§ 201.50 [Amended]

20. Section 201.50 Statement of

identity is amended in paragraph (b) by

removing the second sentence.

§ 201.100 [Amended]

21. Section 201.100 Prescription drugs

for human use is amended in paragraph

(c)(2) by removing the number ‘‘, 506,’’.

PART 207—REGISTRATION OF

PRODUCERS OF DRUGS AND LISTING

OF DRUGS IN COMMERCIAL

DISTRIBUTION

22. The authority citation for 21 CFR

part 207 is revised to read as follows:

Authority: 21 U.S.C. 331, 351, 352, 355,

357, 360, 360b, 371, 374; 42 U.S.C. 262.

§ 207.25 [Amended]

23. Section 207.25 Information

required in registration and drug listing

is amended in paragraphs (b)(2), (b)(5),

and (b)(6) by removing the number

‘‘506,’’ and in paragraph (b)(4) by

removing the number ‘‘, 506,’’.

§ 207.31 [Amended]

24. Section 207.31 Additional drug

listing information is amended in

paragraph (a)(1) by removing the

number ‘‘, 506,’’, and in paragraphs

(a)(2), (a)(3), and (c) by removing the

number ‘‘506,’’.

§ 207.37 [Amended]

25. Section 207.37 Inspection of

registrations and drug listings is

amended in paragraph (a)(2)(i) by

removing the number ‘‘506,’’.

PART 210—CURRENT GOOD

MANUFACTURING PRACTICE IN

MANUFACTURING, PROCESSING,

PACKING, OR HOLDING OF DRUGS;

GENERAL

26. The authority citation for 21 CFR

part 210 is revised to read as follows:

Authority: 21 U.S.C. 321, 351, 352, 355,

357, 360b, 371, 374.

PART 211—CURRENT GOOD

MANUFACTURING PRACTICE FOR

FINISHED PHARMACEUTICALS

27. The authority citation for 21 CFR

part 211 is revised to read as follows:

Authority: 21 U.S.C. 321, 351, 352, 355,

357, 360b, 371, 374.

PART 310—NEW DRUGS

28. The authority citation for 21 CFR

part 310 is revised to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352,

353, 355, 357, 360b–360f, 360j, 361(a), 371,

374, 375, 379e; 42 U.S.C. 216, 241, 242(a),

262, 263b–263n.

PART 312—INVESTIGATIONAL NEW

DRUG APPLICATION

29. The authority citation for 21 CFR

part 312 is revised to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352,

353, 355, 357, 371; 42 U.S.C. 262.

30. The authority citation for 21 CFR

part 312, subpart E is revised to read as

follows:

Authority: 21 U.S.C. 351, 352, 353, 355,

357, 371; 42 U.S.C. 262.

PART 314—APPLICATIONS FOR FDA

APPROVAL TO MARKET A NEW DRUG

OR AN ANTIBIOTIC DRUG

31. The authority citation for 21 CFR

part 314 is revised to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352,

353, 355, 357, 371, 374, 379e.

§ 314.170 [Amended]

32. Section 314.170 Adulteration and

misbranding of an approved drug is

amended in the first sentence by

removing the phrase ‘‘under sections

505, 506, and 507’’ and adding in its

place the phrase ‘‘under sections 505(j)

and 507’’.

§ 314.430 [Amended]

33. Section 314.430 Availability for

public disclosure of data and
Federal Register / Vol. 63, No. 92 /Wednesday, May 13, 1998 / Proposed Rules 26693

information in an application or

abbreviated application is amended in

paragraph (f)(6) by removing the phrase

‘‘under sections 505(j), 506, and 507’’

and adding in its place the phrase

‘‘under sections 505(j) and 507’’.

PART 369—INTERPRETATIVE

STATEMENTS RE WARNINGS ON

DRUGS AND DEVICES FOR OVER–

THE–COUNTER SALE

34. The authority citation for 21 CFR

part 369 is revised to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352,

353, 355, 357, 371.

§ 369.5 [Removed]

35. Section 369.5 Warning required on

insulin intended for over-the-counter

sale is removed

§ 369.21 [Amended]

36. Section 369.21 Drugs; warning

and caution statements required by

regulations is amended by removing the

entry for ‘‘INSULIN’’.

PART 429—DRUGS COMPOSED

WHOLLY OR PARTLY OF INSULIN

37. Under authority of section 701(a)

of the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 371(a)) and section 125(a)

of the Food and Drug Modernization Act

(Pub. L. 105–115), amend Title 21 of the

Code of Federal Regulations by

removing part 429.

PART 800—GENERAL

38. The authority citation for 21 CFR

part 800 is revised to read as follows:

Authority: 21 U.S.C. 321, 334, 351, 352,

355, 357, 360e, 360i, 360k, 361, 362, 371.

PART 812—INVESTIGATIONAL

DEVICE EXEMPTIONS

39. The authority citation for 21 CFR

part 812 is revised to read as follows:

Authority: 21 U.S.C. 331, 351, 352, 353,

355, 357, 360, 360c–360f, 360h–360j, 371,

372, 374, 379e, 381, 382, 383; 42 U.S.C. 216,

241, 262, 263b–263n.

Dated: April 17, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98–12452 Filed 5–12–98; 8:45 am]

BILLING CODE 4160–01–F