[Federal Register Volume 63, Number 92 (Wednesday, May 13, 1998)]
[Rules and Regulations]
[Pages 26694-26699]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-12452]


      

  Federal Register / Vol. 63, No. 92 / Wednesday, May 13, 1998 / Rules 
and Regulations  

[[Page 26694]]



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

AGENCY: Food and Drug Administration, HHS.

ACTION: Direct final rule.

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

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repealed the statutory provision in the Federal Food, Drug, and 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amendments repeal or update out-of-date, noncontroversial regulations 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