[Federal Register Volume 62, Number 199 (Wednesday, October 15, 1997)]
[Rules and Regulations]
[Pages 53536-53538]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-27298]


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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]
RIN 0910-AA93


Revision of the Requirements for a Responsible Head for 
Biological Establishments

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the 
biologics regulations by deleting the requirements for a biologics 
establishment to name a ``responsible head'' or ``designated qualified 
person'' to exercise control of the establishment in all matters 
relating to compliance with regulatory requirements and 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 or possess 
expertise in all matters. This change will provide manufacturers with 
more flexibility in assigning control and oversight responsibility 
within a company. This final 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.

EFFECTIVE DATE: October 15, 1997.

FOR FURTHER INFORMATION CONTACT: Astrid L. Szeto, Center for Biologics 
Evaluation and Research (HFM-17), Food and Drug Administration, 1401 
Rockville Pike, Rockville, MD 20852-1448, 301-594-3074.

SUPPLEMENTARY INFORMATION:

I. Introduction

    In the Federal Register of January 29, 1997 (62 FR 4221), FDA 
published a proposed rule 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.
    Under Sec. 600.10(a) (21 CFR 600.10(a)), a manufacturer of 
biological products currently is required to name a responsible head 
who is to exercise control of the 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 involved in 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 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 better qualified and in a better position to enforce or 
direct the enforcement of discipline and the 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 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 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), 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 revision to the definition of ``manufacturer'' 
in Sec. 600.3 (see 61 FR 24227, May 14, 1996), an applicant may apply 
for and obtain a license for a biological product to be manufactured at 
more than one manufacturing site that may or may not be owned by the 
applicant. Therefore, applicants 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. 
CDER's regulations do not contain an analogous requirement for a 
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. Highlights of the Final Rule

    Under the final rule, an authorized official may be chosen by the 
applicant

[[Page 53537]]

to receive and send correspondence to CBER. The applicant may choose to 
have more than one authorized official. Accordingly, the agency is 
amending Sec. 600.10 by removing and reserving paragraph (a) and 
revising the heading of paragraph (b) to read ``Personnel.'' The agency 
is also amending 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 is amending 
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 removing 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 is removing and reserving Sec. 606.20(a).

III. Comments on the Proposed Rule and FDA Responses

    FDA received 11 comments on the proposed rule, which included 
comments from biological product manufacturers, including blood 
establishments. Eight of the comments fully supported the proposed 
rule.
    Three comments received from the blood industry expressed concern 
that they would no longer have a single responsible head through whom 
they would interact with FDA, and that the responsible persons in the 
organization will have diminished authority and responsibility in 
communication and decisionmaking because their responsibilities and 
authority will no longer be mandated by the regulations.
    FDA does not agree. In the final rule, only the requirement to 
retain a single responsible head is being eliminated. Any applicant 
wishing to have a single authorized representative who would serve the 
function of the responsible head as previously set forth in 
Sec. 600.10(a), may do so. In the past, FDA has often encountered 
circumstances where the responsible head of an establishment was unable 
to adequately carry out her or his responsibilities in assuring that 
the establishment complies with FDA requirements. This failure was 
often due, in part, to the responsible head having inadequate knowledge 
in an area to determine whether FDA's requirements were being met or 
the responsible head was too remote in location or corporate structure 
to adequately monitor activities to assure requirements were being met. 
Removal of this requirement will allow organizations to designate 
responsible individuals with appropriate training and experience to 
provide better communication to the agency as functional experts in 
their respective areas of responsibility. FDA believes that the 
industry should have the flexibility to assign responsibility in a way 
that best fits each applicant's organizational structure as long as the 
public health protection is not diminished.
    Furthermore, the elimination of the requirement for a responsible 
head or designated qualified person does not decrease the duty that 
responsible corporate officers have to ensure compliance with the law. 
(Park, and Dotterweich, supra.)

IV. Effective Date

    The final rule is effective October 15, 1997. As provided under 5 
U.S.C. 553(d) and Sec. 10.40(c)(4) (21 CFR 10.40(c)(4)), the effective 
date of a final rule may not be less than 30 days after the date of 
publication, except for, among other things, ``a regulation that grants 
an exemption or relieves a restriction'' (Sec. 10.40(c)(4)(i)). Because 
this rule will provide greater flexibility in assigning control and 
oversight responsibility within a biological product establishment by 
eliminating the responsible head requirement, FDA believes that an 
immediate effective date is appropriate.

V. Analysis of Impacts

    FDA has examined the impacts of the final 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 final rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the 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.
    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 final 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 final rule will not have a 
significant economic impact on a substantial number of small entities. 
No further analysis is required.

VI. 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.

Lists 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, 21 CFR parts 600, 601, and 606 are 
amended as follows:

[[Page 53538]]

PART 600--BIOLOGICAL PRODUCTS: GENERAL

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

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 360i, 371, 
374; 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 
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: 21 U.S.C. 321, 351, 352, 353, 355, 360, 360c-360f, 
360h-360j, 371, 374, 379e, 381; 42 U.S.C. 216, 241, 262, 263; 15 
U.S.C. 1451-1461.

    4. Section 601.2 is amended by adding a sentence before the last 
sentence in the introductory text of 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: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371, 
374; 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: September 4, 1997.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 97-27298 Filed 10-14-97; 8:45 am]
BILLING CODE 4160-01-F