[Federal Register Volume 63, Number 92 (Wednesday, May 13, 1998)]
[Proposed Rules]
[Pages 26690-26693]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-12452]



[[Page 26689]]

_______________________________________________________________________

Part III





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



_______________________________________________________________________



21 CFR Parts 3, et al.



Removal of Regulations Regarding Certification of Drugs Composed Wholly 
or Partly of Insulin; Proposed Rule and Rule

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

[[Page 26690]]



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 FDAMA repealed the statutory provision in the Federal 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 L. 105-115) repealed section 506 of 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-and-comment 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

[[Page 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-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, 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.


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:


[[Page 26692]]


    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,''.

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

[[Page 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.


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

    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