[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
