Removal of Regulations Regarding Certification of Drugs Composed Wholly or Partly of Insulin

SUMMARY: The Food and Drug Administration (FDA) is repealing its

regulations governing certification of drugs containing insulin and

making conforming amendments to other sections of its 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repealed the statutory provision in the Federal Food, Drug, and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.

FDA is using direct final rulemaking for this action because the agency

expects that there will be no significant adverse comment on the 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amendments repeal or update out-of-date, noncontroversial regulations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. Elsewhere in this issue of the Federal Register,

FDA is publishing a companion proposed rule under FDA's usual procedure

for notice-and-comment rulemaking to provide a procedural framework to

finalize the rule in the event the agency receives significant adverse

comments and withdraws this direct final rule.

DATES: This regulation is effective September 25, 1998. Submit written

comments on or before July 27, 1998. If no timely significant adverse

comments are received, the agency will publish a document in the

Federal Register before August 26, 1998, confirming the effective date

of the direct final rule. If timely significant adverse comments are

received, the agency will publish a document of significant adverse

comment in the Federal Register withdrawing this direct final rule

before August 25, 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

On November 21, 1997, the President signed FDAMA (Pub. L. 105-115).

Section 125(a) of FDAMA repealed section 506 of the act (21 U.S.C.

356). Section 506 was the section of the act under which the agency

certified drugs composed wholly or partly of insulin. Section 125(a) of

FDAMA also removed references to section 506 from section 301(i)(1) and

(j) of the act (21 U.S.C. 331(i)(1) and (j)). Section 301(i) of the act

prohibits fraudulent use of certain labeling required under various

provisions of the act; while section 301(j) prohibits any person from

using, or the unauthorized disclosure of, trade secret information

obtained under authority of various provisions of the act.

Section 125(a) of FDAMA also repealed section 502(k) of the act (21

U.S.C. 352(k)), which provided that any drug that is, or is represented

to be, composed wholly or partly of insulin is misbranded unless it has

been certified or released under authority of section 506 of the act.

FDAMA also removed references to section 506 of the act in section

510(j)(1)(A) and (j)(1)(D) of the act (21 U.S.C. 360(j)(1)(A) and

(j)(1)(D)), which is part of the drug listing provisions of the act,

and section 125(a) of FDAMA amended a law governing procurement of

drugs by certain Federal agencies (38 U.S.C. 8126(h)(2)) by removing a

reference to drugs certified under authority of section 506 of the act.

FDAMA added drugs composed wholly or partly of insulin to the

prohibition in section 801(d) of the act (21 U.S.C. 381(d)) against the

reimportation of prescription drugs except by the original

manufacturer. This amendment to section 801(d) of the act does not

require implementing regulations. FDA will, however, place language

reflecting this provision of FDAMA in relevant sections of a separate

rule implementing the Prescription Drug Marketing Act of 1987 (Pub. L.

100-293). That rulemaking was initiated with the proposed rule

published in the Federal Register of March 14, 1994 (59 FR 11842).

Finally, section 125(c) of FDAMA amended section 802 of the act (21

U.S.C. 382) to exempt insulin drugs from the export requirements of

section 802 if the drugs meet the requirements of section 801(e)(1) of

the act.

II. Direct Final Rulemaking

FDA has determined that the subjects of this rulemaking are

suitable for a direct final rule. The actions taken should be

noncontroversial, and the agency does not anticipate receiving any

significant adverse comments.

The repeal of section 506 of the act eliminated the statutory

provision on which the agency relied to certify drugs composed wholly

or partly of insulin. FDA will, therefore, remove all provisions of

title 21 of the Code of Federal Regulations (CFR) relating to the

certification of insulin products. FDA will also make various

ministerial changes to title 21, such as removing references to section

506 of the act in authority sections and regulations whose subjects are

not certification of insulin.

FDA has also determined that it is appropriate to use direct final

rulemaking to update the definition of insulin in Sec. 200.15 (21 CFR

200.15). The statutory references in the definition are being changed

to reflect changes in the law and the scope of the definition is being

clarified to reflect the existence of new forms of insulin that have

been introduced since the definition was originally issued.

If FDA does not receive significant adverse comment on or before

July 27, 1998, the agency will publish a document in the Federal

Register before August 25, 1998, confirming the effective date 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. If timely significant adverse comments are received,

the agency will publish a document of significant adverse comment in

the Federal Register withdrawing this direct final rule before August

26, 1998.

The companion proposed rule, which is identical to the direct final

rule, provides a procedural framework within which the rule may be

finalized in the event the direct final rule is withdrawn because of

significant adverse comment. The comment period for the direct final

rule runs concurrently with that of the

[[Page 26695]]

companion proposed rule. Any comments received under the companion

proposed rule will be treated as comments regarding the direct final

rule. Likewise, significant adverse comments submitted to the direct

final rule will be considered comments to the companion proposed rule,

and the agency will consider such comments in developing a final rule.

FDA will not provide additional opportunity for comment on the

companion proposed rule.

If a significant adverse comment applies to part of this rule and

that part may be severed from the remainder of the rule, FDA may adopt

as final those parts of the rule that are not the subject of a

significant adverse comment. A full description of FDA's policy on

direct final rule procedures may be found in a guidance document

published in the Federal Register of November 21, 1997 (62 FR 62466).

III. Description of the Rule

The rule eliminates references to section 506 of the act in all

authority citations in 21 CFR, chapter I.

The rule amends the delegation of authority provisions in 21 CFR

part 5 to eliminate provisions dealing with the authority to sign

citizen petitions regarding the certification of insulin, the authority

to certify batches of insulin, and the authority to issue regulations

under section 506 of the act pertaining to drugs containing insulin.

The rule eliminates a reference to section 506(c) of the act in 21

CFR 10.50, which deals with issuance of regulations and orders after an

opportunity for a formal evidentiary public hearing. Former section

506(c) of the act dealt with the issuance of insulin regulations

prescribing tests or methods of assay for batch certification that

differed from those specified in an official compendium.

The rule removes a reference to 21 CFR 429.50, which relates to

suspension of certification services for certain persons, in 21 CFR

16.1, which defines the scope of 21 CFR part 16.

The regulations in 21 CFR 25.31 (see 62 FR 40570 at 40595, July 29,

1997) are amended to eliminate testing and certification of batches of

insulin under section 506 of the act from a list of actions that are

categorically excluded from the requirement to prepare an environmental

assessment or an environmental impact statement.

The rule removes a reference to section 506 of the act in 21 CFR

50.1, which defines the scope of 21 CFR part 50.

This rule amends the statutory references in the definition of

insulin found in Sec. 200.15 to reflect the repeal of sections 502(k)

and 506 of the act; the addition of insulin drug products to the

reimportation provision of section 801(d) of the act by FDAMA; the use

of the term ``insulin'' in the export labeling provisions of section

801(f) of the act, which was added by the Technical Amendments to the

FDA Export Reform and Enhancement Act of August 6, 1996 (Pub. L. 104-

180); and FDAMA's addition of section 802(i) to the act, which exempts

insulin drugs from the export requirements of section 802 of the act.

The new definition also clarifies the scope of the term ``insulin'' to

reflect the existence of synthetic and biotechnologically derived human

insulin. The definition is designed to encompass chemical analogs of

insulin, the first of which, insulin lispro (an Eli Lilly & Co.

product), was recently approved.

The labeling requirements found in part 201 (21 CFR part 201) are

being amended by this rule. Section 201.50(b) is amended to remove a

sentence that refers to labeling requirements contained in part 429 (21

CFR part 429), which is also being eliminated by this rule. A reference

to section 506 of the act is being removed from Sec. 201.100(c)(2).

Several references to section 506 of the act are being removed from

21 CFR parts 207 and 314.

FDA is repealing all of part 429 and those portions of part 369 (21

CFR part 369) that deal with insulin drug products.

Part 429 contains the primary provisions the agency has relied on

to carry out the batch certification of drugs composed wholly or partly

of insulin. Subpart A of part 429 defines key terms used in the insulin

certification regulations; subpart B of part 429 contains packaging and

labeling requirements for products subject to batch certification;

subparts C and D of part 429 contain applicable standards and tests and

methods of assay for determining whether batches of insulin may be

certified; subpart E of part 429 contains the requirements for

submitting a request for certification; subpart F of part 429 contains

the administrative procedures and fees applicable to insulin

certification; and subpart G of part 429 imposes additional

recordkeeping requirements applicable to batch certified insulin

products. With the repeal of section 506 of the act, and the

elimination of the insulin batch certification program, the agency is

eliminating these subparts.

The agency notes that several of the provisions in part 429, such

as those covering packaging and labeling and tests and methods of

assay, could be retained under provisions of the act other than section

506 of the act. However, the agency has determined, as explained in

this section of this document, that it would not be appropriate or

necessary to do so at this time.

The current regulations in Sec. 429.10 require insulin drug

products to be packaged in sterile immediate containers with closures

through which the insulin may be withdrawn with a conventional

hypodermic syringe and needle. Section 429.10 also provides for

distinctive containers for certain insulin drug products, none of which

is currently marketed. Although all insulin drug products are currently

marketed in immediate containers that meet the requirements contained

in Sec. 429.10, there is no assurance that a new, safe, and effective

container/closure system would conform to the regulation. To avoid

having to amend the regulation each time a new, acceptable container/

closure system is developed, the agency is removing Sec. 429.10 and,

instead, will rely on the new drug approval process to approve

appropriate container/closure systems for drug products containing

insulin. Applicants for drug products containing insulin submit

descriptions of the container/closure system with the new drug

application (NDA); FDA reviews the container/closure system for use

with the drug product and, if appropriate, approves its use with the

drug product as part of the NDA approval. This system is used to

approve container/closure systems for most new drug products on the

market today, and it provides the flexibility necessary to provide for

approval of new, safe, and effective container/closure systems.

The current regulations in Secs. 369.21, 429.11, and by cross

reference Sec. 369.5, set out detailed requirements for the labeling of

insulin drug products. The current regulations require, among other

information and warnings, information on potency of the drug product,

expiration date of the lot, storage instructions, instructions on

injecting insulin, and descriptions of how the type of insulin-

containing drug product differs from other types of insulin drug

products.

FDA is removing Secs. 369.5 and 429.11 and those portions of

Sec. 369.21 that apply to insulin drug products, and will rely on the

new drug approval process, in conjunction with the general drug

labeling requirements found in part 201, to establish appropriate

labeling requirements for each drug product containing insulin.

Applicants submit copies of proposed labeling with the

[[Page 26696]]

marketing applications for all new drug products, including those

containing insulin; FDA then reviews the application and, if

appropriate, approves it, after the applicant has made necessary

changes. This system is used to establish labeling for most new drug

products and provides the flexibility necessary to provide adequate

labeling for new types of insulin drug products. Because all currently

marketed insulin drug products are the subject of effective NDA's under

section 505(b) of the act, the labeling of these products is not

expected to change as a result of the removal of these rules.

The current regulations in Sec. 429.12 contain a distinguishing

color scheme, which is outdated. The current system includes

distinguishing colors for 40 units per milliliter strengths of insulin

drug products, which are no longer being marketed. It also provides an

identifying color scheme for insulin zinc globin, which is also not

marketed. Under Sec. 429.12, most of the currently marketed insulin

drug products are identified by the color combination of black and

white, which provides limited usefulness. No provisions are made for

either of the two types of mixtures of human insulin and insulin

suspension isophane currently being marketed or insulin lispro, a human

insulin analogue. Accordingly, FDA is removing Sec. 429.12.

Major insulin manufacturers, working with the International

Diabetes Federation (IDF), have developed a new color coding system in

which each type of insulin would be identified with a distinctive

color. FDA has been favorably impressed with the IDF system. However,

the agency believes that it is administratively more efficient to

remove part 429 in its entirety at this time, and implement the IDF

system in a separate rulemaking proceeding or incorporate it into a

guidance issued under FDA's ``Good Guidance Practices'' published in

the Federal Register of February 27, 1997 (62 FR 8961).

FDA is also removing Sec. 429.25, which establishes standards of

quality and purity for protamine, and Sec. 429.26, which establishes

standards of quality and purity for globin hydrochloride. (No insulin

products using globin hydrochloride are currently being marketed.) FDA

does not, at this time, intend to issue regulations directly

establishing other product standards relating to drugs composed wholly

or partly of insulin. Insulin manufacturers and FDA laboratories use

the requirements set out in the approved NDA for analyzing an insulin

drug product and, where appropriate, the standards set out in the

United States Pharmacopeia (USP).

FDA is also removing Sec. 429.30, which sets out testing and assay

methods. Section 429.30 provides, generally, that insulin injection,

insulin suspension protamine zinc, insulin zinc globin, insulin

suspension isophane, insulin zinc suspension, insulin zinc suspension

prompt, and insulin zinc suspension extended be tested and assayed

according to methods set out in the USP. Section 429.30 also provides

tests for isophane ratio, chloride in globin hydrochloride, sulfate in

protamine, nitrogen, and zinc. At least one of these products (insulin

zinc globin) is no longer marketed. The tests and methods of assay for

the remaining products are either outdated or if still in use, have

been incorporated into the applicable NDA.

FDA intends to avoid the potential for this type of outdated,

codified specification by not proposing at this time regulations

specifying testing or assay methods. Instead, insulin will be required

to conform to all applicable USP monographs and the approved NDA for

each product. This will mean that insulin drug products will be

regulated just as other new drugs are regulated by FDA.

IV. Environmental Impact

The agency has determined under 21 CFR 25.24(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.

V. Analysis of Impacts

FDA has examined the impacts of the direct final 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. As discussed below, the agency believes that this final

rule is consistent with the regulatory philosophy and principles

identified in the Executive Order. In addition, the direct final 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 manufacturers currently 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 direct final 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 Reform 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 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.

VI. Paperwork Reduction Act of 1995

This direct final rule contains no collections of information.

Therefore, clearance by the Office of Management and Budget under the

Paperwork Reduction Act of 1995 is not required.

VII. Request for Comments

Interested persons may, on or before July 27, 1998, submit to the

Dockets Management Branch (address above) written comments regarding

this proposal. 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.

[[Page 26697]]

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-the-counter 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, 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 are 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.

Sec. 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).

Sec. 5.73 [Removed]

4. Section 5.73 Certification of insulin is removed.

Sec. 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.

Sec. 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:

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.

Sec. 16.1 [Amended]

9. Section 16.1 Scope is amended in paragraph (b)(2) by removing

the entry for ``Sec. 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.

Sec. 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.

Sec. 50.1 [Amended]

13. Section 50.1 Scope is amended in the last sentence of paragraph

(a) by removing the number ``506,''.

[[Page 26698]]

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:

Sec. 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.

Sec. 201.50 [Amended]

20. Section 201.50 Statement of identity is amended in paragraph

(b) by removing the second sentence.

Sec. 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.

Sec. 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,''.

Sec. 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,''.

Sec. 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.

Sec. 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''.

Sec. 314.430 [Amended]

33. Section 314.430 Availability for public disclosure of data and

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.

Sec. 369.5 [Removed]

35. Section 369.5 Warning required on insulin intended for over-

the-counter sale is removed.

Sec. 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

Part 429 [Removed]

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.

[[Page 26699]]

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