[Federal Register Volume 62, Number 19 (Wednesday, January 29, 1997)]
[Proposed Rules]
[Pages 4221-4223]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-2238]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 600, 601, and 606

[Docket No. 96N-0395]


Revision of the Requirements for a Responsible Head for 
Biological Establishments

AGENCY:  Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the biologics regulations by deleting the requirements for a biologics 
establishment to name a ``responsible head'' or ``designated qualified 
person'' to represent the establishment in its dealings with FDA. 
Because many manufacturers of biological products are firms that have 
more than one manufacturing location and complex corporate structures, 
it may no longer be practical for one individual to represent a 
manufacturer in all matters. The proposed rule would provide 
manufacturers with more flexibility in assigning control and oversight 
responsibility within a company. This proposed rule is part of FDA's 
continuing effort to achieve the objectives of the President's 
``Reinventing Government'' initiative, and it is intended to reduce the 
burden of unnecessary regulations on industry without diminishing 
public health protection.

DATES:  Comments must be submitted on or before April 29, 1997.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
Rockville, MD 20857. Corporations should submit two copies of any 
comments and individuals may submit one copy. Comments should be 
identified with the docket number found in brackets in the heading of 
this document. Received comments are available for public examination 
in the office above between 9 a.m. and 4 p.m., Monday through Friday.
FOR FURTHER INFORMATION CONTACT: Sharon A. Carayiannis, Center for 
Biologics Evaluation and Research (HFM-630), Food and Drug 
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, 301-594-3074.

SUPPLEMENTARY INFORMATION:

I. Background

    Under Sec. 600.10(a) (21 CFR 600.10(a)), a manufacturer of 
biological products is required to name a ``responsible head'' who is 
to exercise control of the manufacturing establishment in all matters 
relating to compliance with regulations in parts 600 through 680 (21 
CFR parts 600 through 680) and who is to represent the manufacturer in 
all pertinent matters with the Center for Biologics Evaluation and 
Research (CBER). This individual must also have an understanding of the 
scientific principles and techniques related to the manufacture of 
biological products. When FDA announced in the Federal Register of June 
3, 1994 (59 FR 28821 and 28822), the review by CBER of certain 
biologics regulations to identify those regulations that are outdated, 
burdensome, inefficient, duplicative, or otherwise unsuitable or 
unnecessary, Sec. 600.10(a) was included. FDA also held a public 
meeting on January 26, 1995, to discuss the retrospective review effort 
and to provide a forum for the public to voice its comments on the 
retrospective review.
    Many of the comments submitted requested revision or elimination of 
the requirements for a ``responsible head'' in Sec. 600.10(a). The 
majority of the comments supported deletion of the regulation. The 
comments stated that the requirement for a responsible head to be an 
expert in multiple functions and to be responsible for a number of 
facility locations is incompatible with current industry practice. The 
comments added that the list of activities in Sec. 600.10(a) is 
extremely broad and this regulation could be interpreted to require the 
responsible head to have an intimate understanding of a wide variety of 
extremely complex activities. All of these activities require specific 
expertise, and it may not be practical to expect one person to be an 
expert in all of those areas. Some comments addressed the requirement 
that the responsible head be responsible for training and have the 
authority to enforce discipline, stating that direct line supervision 
and management personnel are much better qualified and in a better 
position to ``enforce or direct the enforcement of discipline and 
performance of assigned functions by employees engaged in the 
manufacture of products.'' Many comments requested the designation of 
an alternate responsible head, especially in the situation of multiple 
locations.
    As part of the President's ``Reinventing Government'' initiative, a 
report entitled ``Reinventing the Regulation of Drugs Made From 
Biotechnology'' was issued in November 1995. The report announced 
several initiatives to reduce the burden of FDA regulations on the 
biologics industry without reducing public health protection, including 
a proposal to remove the requirements in Sec. 600.10(a) for a 
``responsible head.'' The proposed revision, reflecting comments 
submitted in response to the January 26, 1995, public meeting, would 
enable firms to designate more than one person to communicate directly 
with FDA on official matters related to the biological products they 
manufacture. The commitment to remove requirements for a ``responsible 
head'' was based on FDA's determination that, with the many changes 
that have occurred in science, technology, and corporate structure, it 
no longer may be practical for most biologics manufacturers to rely on 
one individual to meet the requirements included in Sec. 600.10(a). In 
addition, the responsible corporate officer doctrine, e.g., United 
States v. Park, 421 U.S. 658 (1975); United States v. Dotterweich, 320 
U.S. 277 (1943),

[[Page 4222]]

places the burden of ensuring compliance with the statutes and 
regulations applicable to biological products on corporate officials 
``standing in responsible relation to a public danger.'' (Dotterweich, 
320 U.S. at 281.) Thus, it is not necessary to require manufacturers to 
designate a ``responsible head'' in order to enforce the duty 
responsible corporate officials have to implement measures to ensure 
that violations do not occur. (Park, 421 U.S. at 672.)
    In accordance with a recent revision to the definition of 
``manufacturer'' in Sec. 600.3 (see 61 FR 24227, May 14, 1996), a 
biologics applicant may apply for and obtain a license for a product to 
be manufactured at more than one manufacturing site that may or may not 
be owned by the applicant. Therefore, firms may want to designate more 
than one person with primary responsibility to maintain adequate 
oversight of multiple manufacturing sites and ensure that each is 
conforming to FDA's requirements for current good manufacturing 
practices and the applicable biologics standards. Many biologics 
manufacturers also manufacture drugs that are regulated by the Center 
for Drug Evaluation and Research (CDER) under the Federal Food, Drug, 
and Cosmetic Act whose regulations do not contain an analogous 
requirement for the responsible head. FDA's proposal to revise the 
requirements with respect to a responsible head is an effort to 
harmonize CBER's and CDER's policies and requirements and to keep pace 
with changes in science, technology, and corporate structure.

II. Proposed Rule

     Under the proposed revision, an authorized official would be 
chosen by the applicant to receive and send correspondence to CBER. The 
applicant could choose to have more than one authorized official. 
Accordingly, the agency proposes to amend Sec. 600.10 by removing and 
reserving paragraph (a) and revising the heading of paragraph (b) to 
read ``Personnel''. The agency also proposes to amend Sec. 601.2 
Applications for establishment and product licenses; procedures for 
filing by adding the statement ``The applicant, or the applicant's 
attorney, agent, or other authorized official shall sign the 
application'' in paragraph (a) and new paragraph (c)(6). Finally, the 
agency proposes to amend Sec. 601.25(b)(3)(VIII) by replacing ``signed 
by the responsible head (as defined in Sec. 600.10 of this chapter of 
the licensee)'' with ``signed by an authorized official of the 
licensee''.
    FDA is also proposing to remove Sec. 606.20(a), which contains 
language similar to that in Sec. 600.10(a) and applies to all blood 
establishments, including registered, unlicensed blood establishments. 
Like other components of the biologics industry, the blood industry has 
experienced changes in science, technology, and corporate structure. 
Complex donor and transfusion recipient issues, the evolution of 
sophisticated computerized laboratory and donor equipment, complicated 
serology problems, and state-of-the-art laboratory techniques have all 
contributed to changes within the structure of blood establishments, 
regardless of size. To ensure the quality and safety of the blood 
supply, many blood establishments employ personnel who are experts in 
donor issues, infectious disease, computers, molecular biology, 
serology, transfusion issues, quality control, administration, and 
management. It is no longer practical to expect one individual to have 
expertise in all the subspecialties of transfusion medicine. 
Accordingly, to provide sufficient flexibility for a blood 
establishment to select a person with appropriate training and 
experience to be responsible for each facet of its operation, the 
agency proposes to remove and reserve Sec. 606.20(a).
    FDA intends that a final rule would become effective as soon as 
possible after publication in the Federal Register.

III. Economic Impact

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612). 
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). 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.
    Under the Regulatory Flexibility Act, if a rule has a significant 
impact on a substantial number of small entities, an agency must 
analyze regulatory options that would minimize any significant impact 
of a rule on small entities. The proposed rule would have no compliance 
costs and would not result in any new requirements. Therefore, under 
the Regulatory Flexibility Act (5 U.S.C. 605(b)), the Commissioner of 
Food and Drugs certifies that the proposed rule will not have a 
significant economic impact on a substantial number of small entities. 
No further analysis is required.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.24(a)(8) 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.
    Interested persons may, on or before April 29, 1997, 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.

List of Subjects

21 CFR Part 600

    Biologics, Reporting and recordkeeping requirements.

21 CFR Part 601

    Administrative practice and procedure, Biologics, Confidential 
business information.

21 CFR Part 606

    Blood, Labeling, Laboratories, Reporting and recordkeeping 
requirements.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, it is proposed that 21 CFR parts 600, 
601, and 606 be amended as follows:

PART 600--BIOLOGICAL PRODUCTS: GENERAL

    1. The authority citation for 21 CFR part 600 continues to read as 
follows:

    Authority: Secs. 201, 501, 502, 503, 505, 510, 519, 701, 704 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 
353, 355, 360, 360i, 371, 374); secs. 215, 351, 352, 353, 361, 2125 
of the Public Health Service Act (42 U.S.C. 216, 262, 263, 263a, 
264, 300aa-25).

Sec. 600.10  [Amended]

    2.  Section 600.10 Personnel is amended by removing and reserving

[[Page 4223]]

paragraph (a) and by revising the heading of paragraph (b) to read 
``Personnel.''

PART 601--LICENSING

    3. The authority citation for 21 CFR part 601 continues to read as 
follows:

    Authority: Secs. 201, 501, 502, 503, 505, 510, 513-516, 518-520, 
701, 704, 721, 801 of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 321, 351, 352, 353, 355, 360, 360c-360f, 360h-360j, 371, 374, 
379e, 381); secs. 215, 301, 351, 352 of the Public Health Service 
Act (42 U.S.C. 216, 241, 262, 263); secs. 2-12 of the Fair Packaging 
and Labeling Act (15 U.S.C. 1451-1461).

    4. Section 601.2 is amended by adding a sentence before the last 
sentence in paragraph (a), and by adding new paragraph (c)(6) to read 
as follows:

Sec. 601.2  Applications for establishment and product licenses; 
procedures for filing.

    (a) * * * The applicant, or the applicant's attorney, agent, or 
other authorized official shall sign the application. * * *
 * * * * *
    (c) * * *
    (6) The applicant, or the applicant's attorney, agent, or other 
authorized official shall sign the application.

    5. Section 601.25 is amended by revising the first sentence of 
paragraph (b)(3)(VIII) to read as follows:


Sec. 601.25  Review procedures to determine that licensed biological 
products are safe, effective, and not misbranded under prescribed, 
recommended, or suggested conditions of use.

 * * * * *
    (b) * * * 
    (3) * * * 
    (VIII) If the submission is by a licensee, a statement signed by 
an authorized official of the licensee shall be included, stating 
that to the best of his or her knowledge and belief, it includes all 
information, favorable and unfavorable, pertinent to an evaluation 
of the safety, effectiveness, and labeling of the product, including 
information derived from investigation, commercial marketing, or 
published literature. * * *
 * * * * *

PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD 
COMPONENTS

    6. The authority citation for 21 CFR part 606 continues to read as 
follows:

    Authority: Secs. 201, 301, 501, 502, 505, 510, 520, 701, 704 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351, 
352, 355, 360, 360j, 371, 374); secs. 215, 351, 353, 361 of the 
Public Health Service Act (42 U.S.C. 216, 262, 263a, 264).

Sec. 606.20  [Amended]

    7. Section 606.20 Personnel is amended by removing and reserving 
paragraph (a).

    Dated: January 10, 1997.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 97-2238 Filed 1-28-97; 8:45 am]
BILLING CODE 4160-01-F