Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64607

from seeds that have been irradiated

need not be labeled as treated by

irradiation where the sprouts

themselves have not been irradiated.

Based on the data and studies

submitted in the petition and other

information in the agency’s files, FDA

concludes that: (1) The proposed use of

irradiation on seeds for sprouting at

levels not to exceed 8 kGy is safe, (2) the

irradiation will achieve its intended

technical effect, and therefore, (3) the

regulations in § 179.26 should be

amended as set forth below.

In accordance with § 171.1(h) (21 CFR

171.1(h)), the petition and the

documents that FDA considered and

relied upon in reaching its decision to

approve the petition are available for

inspection at the Center for Food Safety

and Applied Nutrition by appointment

with the information contact person

listed above. As provided in § 171.1(h),

the agency will delete from the

documents any materials that are not

available for public disclosure before

making the documents available for

inspection.

This 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.

IV. Environmental Impact

The agency has determined under 21

CFR 25.32(j) 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. Objections

Any person who will be adversely

affected by this regulation may at any

time file with the Dockets Management

Branch (address above) written

objections by November 29, 2000. Each

objection shall be separately numbered,

and each numbered objection shall

specify with particularity the provisions

of the regulation to which objection is

made and the grounds for the objection.

Each numbered objection on which a

hearing is requested shall specifically so

state. Failure to request a hearing for

any particular objection shall constitute

a waiver of the right to a hearing on that

objection. Each numbered objection for

which a hearing is requested shall

include a detailed description and

analysis of the specific factual

information intended to be presented in

support of the objection in the event

that a hearing is held. Failure to include

such a description and analysis for any

particular objection shall constitute a

waiver of the right to a hearing on the

objection. Three copies of all documents

shall be submitted and shall be

identified with the docket number

found in brackets in the heading of this

document. Any objections received in

response to the regulation may be seen

in the Dockets Management Branch

between 9 a.m. and 4 p.m., Monday

through Friday.

VI. References

The following references have been

placed on display at the Dockets

Management Branch (address above)

and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday

through Friday.

1. FDA Memorandum, K. Morehouse to J.

Ziyad, February 23, 2000.

2. FDA Memorandum, I. Chen to J. Ziyad,

February 28, 2000.

3. FDA Memorandum, M. Walderhaug to J.

Ziyad, December 15, 1999.

List of Subjects in 21 CFR Part 179

Food additives, Food labeling, Food

packaging, Radiation protection,

Reporting and recordkeeping

requirements, Signs and symbols.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, and redelegated to

the Director, Center for Food Safety and

Applied Nutrition, 21 CFR part 179 is

amended as follows:

PART 179—IRRADIATION IN THE

PRODUCTION, PROCESSING AND

HANDLING OF FOOD

1. The authority citation for 21 CFR

part 179 continues to read as follows:

Authority: 21 U.S.C. 321, 342, 343, 348,

373, 374.

2. Section 179.26 is amended in the

table in paragraph (b) by adding entry

‘‘10.’’ under the headings ‘‘Use’’ and

‘‘Limitations’’ to read as follows:

§ 179.26 Ionizing radiation for the

treatment of food.

* * * * *

(b) * * *

Use Limitations

*******

10. For control of microbial pathogens on seeds for sprouting. Not to exceed 8.0 kGy.

* * * * *

Dated: October 20, 2000.

L. Robert Lake,

Director of Regulations and Policy, Center

for Food Safety and Applied Nutrition.

[FR Doc. 00–27735 Filed 10–27–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 314 and 601

[Docket No. 99N–1852]

Postmarketing Studies for Approved

Human Drug and Licensed Biological

Products; Status Reports

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is revising the

requirements for annual postmarketing

status reports for approved human drug

and biological products, and is requiring

applicants to submit annual status

reports for certain postmarketing studies

of licensed biological products. This

rule describes the types of

postmarketing studies covered by these

status reports, the information to be

included in the reports, and the type of

information that FDA would consider

appropriate for public disclosure. This

action will implement the Food and

Drug Administration Modernization Act

of 1997 (FDAMA).

DATES: This rule is effective February

27, 2001.

64608 Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations

FOR FURTHER INFORMATION CONTACT:

Sharon T. Risso, Center for Biologics

Evaluation and Research (HFM–

500), Food and Drug

Administration, 1401 Rockville

Pike, Rockville, MD 20852–1448,

301–827–5098; or

James L. Cobbs, Center for Drug

Evaluation and Research (HFD–

102), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–

5922.

SUPPLEMENTARY INFORMATION:

I. Background

A. Statutory Requirements

Section 130(a) of FDAMA (Public Law

105–115) amended the Federal Food,

Drug, and Cosmetic Act (the act) by

adding a new provision on reports of

postmarketing studies (section 506B of

the act (21 U.S.C. 356b)). Section 506B

of the act provides FDA with additional

authority for monitoring the progress of

postmarketing studies that applicants

have made a commitment to conduct

and requires the agency to make

publicly available information that

pertains to the status of these studies.

The following summary describes the

obligations of applicants and of FDA

under section 506B of the act.

1. Submission of Annual Reports to

FDA Under Section 506B of the Act

Any applicant that has committed to

conduct a postmarketing study for a

drug or biological product that is

approved for marketing must submit to

FDA a report on the progress of the

study or the reasons for the failure of the

applicant to conduct the study. The

applicant must submit the report within

a year after the approval of the product

and annually thereafter on the

anniversary of the product’s U.S.

approval until the study is completed or

terminated. This provision applies to

commitments for postmarketing studies

that were made on or after enactment of

FDAMA, as well as commitments made

before enactment of FDAMA.

2. Special One-Time Reporting

Requirement Under Section 506B of the

Act

An applicant must submit an initial

report to FDA for study commitments

made before November 21, 1997, within

6 months after the effective date of the

final rule. Subsequent to the initial

report, an applicant must submit an

annual report to the agency on the

anniversary of the product’s U.S.

approval. For those applicants required

to submit an annual report 7 to 12

months after the effective date of the

final rule, the submission of the initial

report to FDA within 6 months after the

effective date of the final rule is an

additional one-time burden.

3. FDA Obligations Under Section

506B(c) of the Act

FDA must develop and publish

annually in the Federal Register a

report on the status of postmarketing

study commitments.

4. FDA Obligation Under FDAMA

(Section 130(b))

FDA must submit a specific report to

Congress by October 1, 2001, that

contains the following:

1. A summary of the status reports

submitted under section 506B of the act;

2. An evaluation of the performance

of applicants in fulfilling their

commitments to conduct postmarketing

studies under this provision;

3. FDA’s timeliness in reviewing these

postmarketing studies; and

4. Any legislative recommendations

regarding postmarketing studies.

B. Proposed Rule

FDA published a proposed rule in the

Federal Register of December 1, 1999

(64 FR 67207), that would revise the

requirements for annual postmarketing

status reports for drug and biological

products, and that would require

applicants to submit annual status

reports for certain postmarketing studies

of licensed biological products. The

proposed rule described the types of

postmarketing studies covered by these

status reports, the information to be

included in the reports, and the type of

information that FDA would consider

appropriate for public disclosure. The

agency proposed this action to

implement section 130 of FDAMA. In

proposed §§ 314.81(b)(2)(vii) and

(b)(2)(viii), and 601.70(b), FDA would

require that a status report for a

postmarketing study contain the

following information:

1. Applicant’s name.

2. Product name. This would include

the approved product’s established/

proper name and proprietary name, if

applicable.

3. New drug application (NDA)

number, abbreviated new drug

application (ANDA) number, biologics

license application (BLA) reference

number, or supplement number for the

approved product.

4. Date of product’s U.S. approval.

5. Date of postmarketing study

commitment.

6. Description of postmarketing study

commitment. For clinical studies, this

section would include the purpose of

the postmarketing study, the patient

population addressed by the study, the

number of patients and/or subjects to be

included in the study, and the

indication and dosage(s) that are to be

studied. For nonclinical studies, this

section would include the type and

purpose of the study (e.g.,

carcinogenicity study to determine

effects of chronic dosing).

7. Schedule for conduct, completion,

and reporting of the postmarketing

study commitment. This section would

include projected dates for initiation of

the different phases of the study, for

completion of the study, and for

submission of the final study report to

FDA. If the original schedule is revised

under section 9 of this status report, the

revised schedule would also be reported

in this section (i.e., section 7) in the

next status report with a note indicating

that the schedule has been revised as

reported in the previous status report.

8. Current status of the postmarketing

study commitment. Applicants would

categorize the status of each

postmarketing study using one of the

following terms that describe the study’s

status on the U.S. anniversary date of

approval of the application or other

agreed date:

a. Pending. The study has not been

initiated (i.e., first patient has not been

enrolled).

b. Ongoing. The study is proceeding

according to, or ahead of, the original

schedule described in section 7 of the

status report. If a study has been

completed but the final study report has

not been submitted to FDA, the date the

study was completed would be

provided.

c. Delayed. The study is proceeding

but is behind the original schedule

described in section 7 of the status

report.

d. Terminated. The study was ended

before completion.

e. Submitted. The study has been

completed (i.e., last patient finished the

protocol) or terminated and a final study

report has been submitted to FDA. This

category would include the date the

final study report was submitted to

FDA.

9. Explanation of the study’s status.

This section would include a brief

description of the status of the study,

including the number of patients and/or

subjects enrolled to date and an

explanation of the study’s status

identified under section 8 of the status

report (e.g., delayed due to difficulty in

patient accrual, terminated because

study would no longer provide useful

information, terminated because study

is no longer feasible, terminated because

of adverse events or other safety issues

associated with the use of the product).

Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64609

If the schedule under section 7 of the

status report has changed since the last

annual report, this section would also

include a revised schedule, as well as

the reason(s) for the revision.

FDA invited the public to submit

written comments on the proposed rule

by February 14, 2000, and on the

information collection provisions by

January 3, 2000. Comments received

have been considered and are discussed

in section III of this document. No

comments were received on the

information collection provisions.

C. Availability of Guidance

To help applicants comply with the

requirements of this final rule, the

agency is developing a guidance for

industry entitled ‘‘Reports on the Status

of Postmarketing Studies—

Implementation of section 130 of the

Food and Drug Administration

Modernization Act of 1997.’’ FDA

intends to make a draft of this guidance

available shortly after publication of this

final rule.

II. Description of the Final Rule

This final rule amends parts 314 and

601 (21 CFR parts 314 and 601) to revise

the status reports section of

postmarketing annual reports for drug

and licensed biological products

(§§ 314.81(b)(2)(vii) and 601.28). This

final rule also amends part 601 to

require applicants with licensed

biological products to submit a separate

annual report that describes the status of

certain postmarketing studies (§ 601.70).

The major provisions of the final rule

are summarized below.

Under §§ 314.81(b)(2)(vii) and

601.70(a), the final rule defines

postmarketing studies for which status

reports must be submitted to FDA under

section 506B of the act as those that

concern: (1) Clinical safety; (2) clinical

efficacy; (3) clinical pharmacology; and

(4) nonclinical toxicology studies that

are either required by FDA (e.g.,

accelerated approval clinical benefit

studies, pediatric studies) or committed

to by the applicant, in writing, at the

time of approval of an application or a

supplement or after approval of an

application or supplement. FDA is

including clinical safety and efficacy

and clinical pharmacology studies

within the scope of this rule because

these types of studies provide the most

relevant and useful additional

information about the risks, benefits,

and optimal use of an approved drug or

licensed biological product. FDA also is

including nonclinical toxicology studies

within the scope of this rule, although

such studies are not performed on

human subjects, because they are

important to the further evaluation of

the safety of a marketed drug or

biological product. For the purpose of

this rule, clinical safety and clinical

efficacy studies include human

epidemiological studies. Clinical

pharmacology studies include

pharmacokinetic and pharmacodynamic

studies.

Under §§ 314.81(b)(2)(vii) and 601.70,

the final rule requires applicants to

provide status reports to FDA regarding

the progress of the postmarketing

studies described above. In addition,

under § 314.81(b)(2)(viii), applicants

with approved NDA’s and ANDA’s must

provide status reports for any

postmarketing study not reported under

§ 314.81(b)(2)(vii) (e.g., chemistry,

manufacturing, controls, product

stability). These include postmarketing

studies performed by, or on behalf of,

the applicant on its own initiative.

Section 314.81(b)(2)(viii) does not

represent a new reporting burden for

applicants with approved NDA’s or

ANDA’s because these applicants are

currently required to provide status

reports on postmarketing studies in

annual reports. FDA is not requiring a

similar reporting requirement for

postmarketing studies of licensed

biologicals in this rule. However,

applicants with licensed biological

products may voluntarily submit status

reports to FDA for postmarketing

studies that are not required to be

reported under § 601.70.

The agency is committed to

harmonizing its reporting requirements

for drugs and biologics as much as

possible. FDA considered amending its

biologics regulations to require the

submission of information in

postmarketing annual reports currently

submitted to the agency by applicants

with approved NDA’s and ANDA’s

under § 314.81(b)(2)(i) through (b)(2)(vi).

FDA also considered combining

postmarketing annual reports required

under §§ 601.12(d), 601.28, and

proposed 601.70 into a single annual

report that would include additional

information as required in

§ 314.81(b)(2)(i) through (b)(2)(vi).

However, FDA has determined that

requiring such additional information is

beyond the scope of this rulemaking,

and that it is appropriate, at this time,

to harmonize only the drugs and

biologics postmarketing annual

reporting requirements as they relate to

section 506B of the act.

III. Comments on the Proposed Rule

and FDA Responses

FDA received seven comments on the

proposed rule from representatives of

pharmaceutical companies and

associations. While most comments

agreed that the proposed rule

appropriately implements section 130 of

FDAMA, many comments expressed

concern about what information should

be included in the status reports and

what information should be disclosed to

the public.

A discussion of the comments on the

proposed rule and the agency’s

responses follows.

A. Status Reports

(Comment 1) One comment claimed

that the proposed content of status

reports exceeds that necessary to

determine, as stated in section 130 of

FDAMA, ‘‘the progress of the study or

the reasons for the failure of the sponsor

to conduct the study.’’ The comment

said that the agency turns the simple

reporting requirement contemplated by

FDAMA into a potentially complicated

and burdensome exercise. For example,

the comment noted that applicants must

provide detailed information on a

postmarketing study commitment

regarding the purpose of the study, the

patient population addressed by the

study, the indication and dosage(s) that

are to be studied, the projected dates for

initiation of the different phases of the

study and completion of the study, the

status of patient accrual, as well as an

explanation of the study’s status (which

would be categorized separately). The

comment recommended that the

proposed rule be revised to require

applicants to simply identify a pertinent

postmarketing study commitment and

report on its status using a standardized

description. The comment added that

additional details regarding the

postmarketing study commitment

should be provided at the discretion of

the applicant.

FDA has reviewed the proposed

content for status reports and has

decided to make several changes. In

§§ 314.81(b)(2)(vii)(a)(6) and

601.70(b)(6), the agency is revising the

requirements for the ‘‘Description of

postmarketing study commitment’’

section of status reports to permit an

applicant to determine the type of

information that is necessary to identify

a postmarketing study commitment.

Instead of specifying the elements that

would be required to be included in this

section, the provision now provides

examples of the type of information that

applicants may choose to use to

describe a postmarketing study

commitment. This section, as revised,

now reads:

The description must include sufficient

information to uniquely describe the study.

This information may include the purpose of

the study, the type of study, the patient

64610 Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations

population addressed by the study and the

indication(s) and dosage(s) that are to be

studied.

The list of examples does not contain

‘‘the number of patients and/or subjects

to be included in the study.’’ However,

an applicant is required to include

patient accrual information (by

providing the number of patients or

subjects enrolled to date and the total

planned enrollment) in the section

requiring an explanation of the study’s

status.

The agency recognizes that the extent

of information necessary to identify

various postmarketing study

commitments will vary. In most cases,

it will be sufficient to use the language

provided in the FDA document

describing the postmarketing study

commitment (e.g., action letter). In other

cases, such as when multiple studies are

required to fulfill a postmarketing study

commitment, additional information is

likely to be needed to describe each of

the studies.

In §§ 314.81(b)(2)(vii)(a)(7) and

601.70(b)(7), the agency is revising the

‘‘Schedule of conduct, completion and

reporting of the postmarketing study

commitment’’ section of the status

report to require inclusion of only the

information that is most important in

determining the progress of a study and

to clarify that information. FDA is

replacing the phrase ‘‘projected dates for

initiation of the different phases of the

study’’ with the phrase ‘‘actual or

projected dates for submission of the

study protocol to FDA, completion of

patient accrual or initiation of an animal

study’’ and adding ‘‘any additional

milestones or submissions for which

projected dates were specified as part of

the commitment.’’ FDA recognizes

study phases may vary depending on

the type of study and the study design.

Because information on some phases of

a study may not be meaningful in

establishing study progress, FDA is

limiting the information for this section

to the projected, or actual, dates for the

submission of the study protocol to

FDA; for completion of patient accrual

into a clinical study or initiation of an

animal study; for completion of the

study; and for submission of the final

study report to FDA. In addition, FDA

recognizes that some study

commitments include an agreement to

report important intermediate

timepoints or early study endpoints

(e.g., evaluation of surrogate endpoints

in a study also measuring clinical

benefit). If a study commitment includes

reporting at such intermediate

timepoints, these timepoints should be

included in the projected schedule

submitted under

§§ 314.81(b)(2)(vii)(a)(7) and

601.70(b)(7).

FDA is requiring that the schedule in

this section include actual dates, if they

represent milestones that have already

been reached, in addition to projected

dates. This is particularly appropriate

for studies that were started before the

effective date of this final rule and for

which a particular aspect of the study

has already been completed by the

effective date. Actual dates are also

appropriate if a particular aspect of the

study (e.g., submission of study

protocol) was completed prior to

approval of the drug or agreement on

the postmarketing commitment.

The agency is revising the section title

‘‘Schedule for conduct, completion and

reporting of the postmarketing study

commitment’’ by removing the word

‘‘conduct’’ from the section heading.

FDA is making this revision because the

word ‘‘conduct’’ is not necessary.

FDA is modifying the section

‘‘Current status of the postmarketing

study commitment’’ at

§§ 314.81(b)(2)(vii)(a)(8) and

601.70(b)(8), by removing from the

paragraph ‘‘Ongoing’’ the requirement to

include the date the study was

completed, and removing from the

paragraph ‘‘Submitted’’ the requirement

to provide the date the final study report

was submitted to FDA. These date

requirements have been added to the

section ‘‘Explanation of the study’s

status’’ at §§ 314.81(b)(2)(vii)(a)(9) and

601.70(b)(9) to consolidate under this

section all information providing

clarification of the status of individual

studies. The paragraph ‘‘Pending’’ has

been clarified to state that studies that

have not been initiated will be

categorized as delayed if the study is

behind the original schedule for

completion and reporting of the

postmarketing commitment. FDA is

modifying the paragraph ‘‘Terminated’’

to clarify that this category is to be used

if a study has been terminated before

completion, but a final study report has

not yet been submitted to the agency.

FDA is requiring, as proposed, that

annual status reports include the

applicant’s name, product name,

application (NDA, ANDA, BLA, and

supplement) number, date of

postmarketing commitment, and the

product approval date. However, in

§§ 314.81(b)(2)(vii)(a)(4) and

601.70(b)(4), the agency is replacing the

‘‘Date of product’s U.S. approval’’

section heading with the heading ‘‘Date

of U.S. approval of NDA, ANDA, or

BLA.’’ This change is being made to

clarify identification of the

postmarketing commitment because the

product may be included in more than

one application.

FDA is keeping all other sections of

the status reports as proposed, because

the agency believes that the information

that is being requested in them is

necessary to identify a postmarketing

study commitment, to establish the

progress of a postmarketing study

commitment, or to identify the reasons

for the failure of the applicant to

conduct the study. The agency will use

these status reports to review the

progress of postmarketing study

commitments and to meet its statutory

reporting obligations (i.e., its report to

Congress on this topic by October 1,

2001, and its annual report in the

Federal Register on the status of

postmarketing study commitments).

FDA anticipates that preparation of a

status report for a postmarketing study

commitment will not be burdensome.

Each status report should contain no

more than one page of information that

is readily available to the applicant.

(Comment 2) One comment said that

much of the information required to be

submitted in an NDA annual report

under the proposed rule must already be

submitted to an investigational new

drug application (IND). The comment

noted that the risk of duplicative

reporting burdens is exacerbated by the

fact that NDA and IND anniversary

dates may differ and applicants may be

required to collect and reconcile

information for the same postmarketing

studies twice a year. The comment

recommended that FDA scale back the

scope of the information required to be

submitted to the NDA annual report and

also permit applicants to reference

pertinent sections of an IND and IND

annual report in an NDA annual report.

FDA declines to permit applicants to

reference their IND and IND annual

reports in the status report section of

NDA and BLA annual reports. Most of

the information contained in these

reports is different from the information

submitted to the IND and is used by the

agency for different purposes. FDA

needs the information that is contained

in a status report in the prescribed

format to meet its statutory reporting

obligations. FDA does not believe that

preparation of status reports will be

unduly burdensome for applicants, and

the fact that no comments were

submitted on the information collection

provisions supports this conclusion.

B. Public Disclosure of Information

New §§ 314.81(b)(2)(vii)(b) and

601.70(e) require the agency to publicly

disclose any information concerning a

postmarketing study if the agency

determines that the information is

Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64611

necessary to identify the applicant or to

establish the status of the study,

including the reasons, if any, for failure

to conduct, complete, and report the

study. The proposal stated that

information necessary to establish the

status of a postmarketing study would

include the study protocol, patient

accrual rates, reports of unexpected

suspected adverse drug reactions, and

study results. The proposal also

specified that FDA would not publicly

disclose trade secrets, as defined in

§ 20.61 (21 CFR 20.61), or information,

described in § 20.63 (21 CFR 20.63), the

disclosure of which would constitute an

unwarranted invasion of personal

privacy.

(Comment 3) Three comments

strongly objected to the public

disclosure provisions of the proposed

rule contending that such disclosure

could potentially result in release of

confidential and highly sensitive

commercial information. One comment

said that the ‘‘proposed rule directly

violates the limits set by FDAMA,’’

when the proposed rule calls for the

disclosure of the study protocol, patient

accrual rates, reports of unexpected

suspected adverse drug reactions, and

study results. The comment claimed

that the agency is incorrect when it

asserts that this additional information

is ‘‘necessary to identify the applicant

and to establish the status of a study.’’

Another comment noted that there is an

inconsistency in the content of the

status reports section and the public

disclosure sections of the proposed rule

that needs clarification. The content of

the status report section is limited to

patient accrual and study status,

whereas the public disclosure section

states that the study protocol and study

results will be made public.

The comments recommended that

study protocols, reports of unexpected

suspected adverse drug reactions, and

results of the study not be publicly

disclosed. One comment said that

clinical protocols are highly proprietary

in terms of design and analytical plan

and that applicants should only be

required to provide a general

description of the study for public

disclosure. Another comment said that

with regard to disclosure of study

results in an orphan drug exclusivity

situation, the publication of detailed

study results may allow competitors to

strategically redesign clinical trials in an

effort to nullify another company’s

market exclusivity. The comment also

said that detailed knowledge of study

results could also lead to potential

disputes between competitors via

negative advertising. The comment

recommended that applicants only be

required to provide a brief summary of

the study results for public disclosure.

Another comment said that disclosure

of study results represents bad science

because it is generally not appropriate to

‘‘peek’’ at results from a study before its

scheduled completion. Another

comment said that annual public

disclosure of all reports of unexpected

adverse drug reactions are inappropriate

for epidemiological studies because no

scientifically-based conclusions can be

drawn when safety reports are reviewed

out of context of the study population

and without regard to the appropriate

controls. However, the comment noted

that if any new association is

established between a product and a

previously unknown adverse reaction,

such information should be made

public. Another comment noted that if

a study is delayed because of low

patient accrual rates, despite legitimate

efforts to enroll subjects, information

posted on a website could negatively

affect the company and its ability to

complete the commitment.

FDA has considered these comments

and agrees that disclosure of the study

protocol, reports of unexpected

suspected adverse drug reactions, and

the results of studies reported under

§§ 314.81(b)(2)(vii) and 601.70 are not

necessary to achieve the purposes of the

rule or section 130 of FDAMA. Section

130 of FDAMA requires the agency to

publicly disclose information pertaining

to status reports if that information is

necessary to identify the applicant and

to establish the status of a study,

including the reasons, if any, for failure

to conduct, complete, and report the

study. FDA has, therefore, decided to

remove the following sentence from

proposed §§ 314.81(b)(2)(vii)(b) and

601.70(e): ‘‘Information necessary to

establish the status of a postmarketing

study includes the study protocol,

patient accrual rates, reports of

unexpected suspected adverse drug

reactions, and study results.’’

For purposes of public disclosure, the

agency intends to release information

that establishes the status of a study and

that is contained in

§§ 314.81(b)(2)(vii)(a)(1) through

(b)(2)(vii)(a)(9) and 601.70(b)(1) through

(b)(9) of the final rule. These sections do

not call for study results and FDA does

not believe that any information

provided by applicants in these sections

of a status report would be considered

confidential commercial information.

However, even if an applicant considers

certain information in these sections to

be confidential commercial information,

section 130(a) of FDAMA would

authorize FDA to release such

information if it were necessary to

identify the applicant or to establish the

status of a study, including the reasons,

if any, for failure to conduct, complete,

and report the study. The agency has

decided that a study protocol, study

results, and reports of unexpected

suspected adverse drug reactions are not

information necessary to establish the

status of the study. However, the agency

expects to continue to receive study

protocols and study results since that

information is necessary for FDA to

determine whether a study commitment

has been satisfied. The agency also

expects to continue to receive reports of

unexpected suspected adverse drug

reactions, which are required reports.

Other laws, such as the Freedom of

Information Act (FOIA), would

determine whether the agency would

release to the public study protocols,

study results, and reports of unexpected

suspected adverse drug reactions.

FDA believes that the number of

patients who are enrolled in a

postmarketing study is an important

factor establishing the status of a study.

Applicants would provide such

information to FDA in status reports,

and, under section 130 of FDAMA,

patient accrual rates would be

considered to be public information.

(Comment 4) One comment claimed

that the proposed rule is contrary to

FOIA and the Trade Secrets Act. The

comment said that FOIA specifically

exempts confidential commercial

information from public disclosure

under 5 U.S.C. 552(b)(4) (so-called

‘‘FOIA Exemption 4’’) and that the

Trade Secrets Act makes it a crime for

a Federal employee to disclose any

information within the scope of FOIA

Exemption 4, including confidential

commercial information to the extent

that the disclosure is not authorized by

law (18 U.S.C. 1905). The comment

further asserted that there is nothing in

the legislative history of FDAMA to

suggest that Congress intended to make

public information that would

otherwise be exempt from disclosure

under FOIA, except to the very narrow

extent necessary to identify a sponsor

and establish the status of a study. The

comment said that the only information

that should be required to be disclosed

should be basic information to identify

the study and sponsor, and the

standardized information on the status

of a study (or, if applicable, a brief

explanation of why a study was not

conducted). The comment said that this

is the only information that should be

posted on FDA’s website.

FDA disagrees with the comment

because it does not believe that status

reports would contain confidential

commercial information. In any event,

64612 Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations

section 130(a) of FDAMA requires the

agency to disclose certain information

from postmarketing study reports even

if that information ordinarily would be

considered confidential commercial

information. Since section 130(a) of

FDAMA requires disclosure, the

disclosure would be authorized by law

and not prohibited by the Trade Secrets

Act. FDA will not disclose any

information from postmarketing study

reports that is considered a trade secret

as defined in § 20.61(a) and section

301(j) of the act (21 U.S.C. 331(j)) or

would constitute an unwarranted

invasion of personal privacy as defined

in § 20.63.

(Comment 5) Two comments wanted

to know what information would be

disclosed on FDA’s website and what

format would be used for this purpose.

One of the comments asked if a

company would have the opportunity to

review information before it is posted

on the website to ensure that

confidential data are not disclosed.

Another comment requested that an

efficient procedure be established to

identify the information that is

disclosable. The comment said that

applicants should be instructed to

include a section in their postmarketing

status reports that is specifically

intended for public disclosure. The

comment noted that this approach is

consistent with that adopted recently by

FDA for information provided by

sponsors to advisory committees in

connection with open advisory

committee meetings. The comment also

noted that if FDA disagrees with an

applicant’s designation of disclosable

information, the agency could then

consult with the applicant.

FDA intends to include information

on its webpage that is provided to FDA

by applicants in their status reports. In

the proposed rule, FDA stated that the

website will contain, at a minimum, the

following information for each

postmarketing study commitment:

Name of the applicant, application

number, product name, dosage form,

product use category, type of study,

commitment description, commitment

date, projected study completion date,

current status of commitment, applicant

summary of status, annual report due

date, and date annual report received.

At this time, FDA intends to include

this information on FDA’s webpage, as

well as the date the final study report is

received by the agency. In the future,

FDA may decide to add or remove types

of information from the website or to

revise the format. FDA intends to

provide a suggested format for

postmarketing reports and an example

of what information will appear on the

agency website in the guidance the

agency is developing or on which the

agency will solicit public comment. (See

section I.C of this document.)

With regard to the submission of a

publicly releasable version of the status

report by applicants, the agency will not

require such submissions at this time.

FDA is considering recommending, in

guidance, that applicants include with

their status reports a publicly releasable

version of the report. This version of the

status report would facilitate FDA’s

transmission of information to its

website.

(Comment 6) One comment said that

the agency needs to clarify that public

disclosure does not apply to chemistry,

manufacturing, and controls (CMC)

studies. Another comment said that the

agency needs to clarify that public

disclosure does not apply to the log of

outstanding regulatory business section

of approved NDA annual reports.

The rule has been clarified to require

the status of CMC studies that the

applicant has agreed to conduct to be

reported under § 314.81(b)(2)(viii). FDA

would not publicly disclose in its

annual Federal Register report or

website information concerning

postmarketing study commitments

submitted in NDA annual reports under

§§ 314.81(b)(2)(viii) and 314.81(b)(2)(ix).

FDA intends to limit information in the

annual Federal Register report and

website to information submitted in

status reports under §§ 314.81(b)(2)(vii)

and 601.70.

C. Scope of Proposed Rule—FDAMA

130 Studies for Drug and Licensed

Biological Products

Annual reports submitted under

§ 314.81(b)(2) apply to human drug

products with an approved NDA or

ANDA. New § 601.70 applies to human

licensed biological products that meet

the definition of ‘‘drug’’ under the act;

it would not apply to biological

products that meet the definition of

‘‘medical device’’ under the act. Revised

§ 314.81(b)(2)(vii) and new § 601.70

require, under section 130 of FDAMA,

status reports of postmarketing studies

concerning clinical safety, clinical

efficacy, clinical pharmacology, and

nonclinical toxicology that are required

by FDA (e.g., accelerated approval

clinical benefit studies and pediatric

studies) or that the applicant committed

to conduct, in writing, either at the time

of approval of an application for the

drug product or licensed biological

product or of a supplement to an

application, or after approval of an

application or a supplement.

(Comment 7) One comment requested

that reporting on the status of

nonclinical studies (e.g., preclinical) be

made optional for § 601.70.

FDA disagrees with the comment. The

agency is requiring that information be

provided for postmarketing nonclinical

toxicology studies because of their

significance in assessing the safety of

drug and licensed biological products.

(Comment 8) One comment said that

FDA should set some reasonable limit

on how far back in time it will require

applicants to report on studies that they

committed to conduct years before

enactment of section 130 of FDAMA but

that still remain open. The comment

suggested that the agency could remove

the status report requirement for a study

commitment that was entered into more

than 3 years ago.

FDA disagrees with the comment.

Section 130 of FDAMA requires that the

status of postmarketing study

commitments, whether entered into

before or after the date of enactment of

FDAMA, be reported to FDA annually

until the commitment is completed or

terminated. Many clinical studies take

several years to complete. Studies that

applicants committed to conduct several

years ago are only now coming to

completion and will yield important

information about the safety and

effective use of the drug or biological

product. The agency will monitor an

applicant’s submission of status reports

under §§ 314.81(b)(2)(vii) and 601.70 for

any postmarketing study commitment

that the agency has formally tracked in

agency postmarketing commitment data

bases.

D. Scope of Proposed Rule—Other

Studies for Drug Products

In § 314.81(b)(2)(viii), FDA proposed

to require that status reports be

submitted for any postmarketing study

not included under § 314.81(b)(2)(vii)

that is being performed by, or on behalf

of, the applicant. The applicant was to

provide the information prescribed

under § 314.81(b)(2)(vii) for each of the

postmarketing studies subject to

reporting.

(Comment 9) Three comments

requested that the agency remove this

section from the regulations because

section 130 of FDAMA only requires

status reports for studies that a company

has committed to FDA to perform. One

of the comments said that, as an

alternative, the agency could limit the

studies in this section to those which

the applicant committed to FDA that it

would conduct.

FDA disagrees with the comment. The

agency currently requires that the status

of any postmarketing studies performed

by, or on behalf of, the applicant be

provided in NDA annual reports and

Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64613

FDA will continue to require status

reports for these studies. It was not the

intent of this rule, however, to expand

current reporting requirements for

postmarketing studies reported under

§ 314.81(b)(2)(viii). In considering the

comments received, FDA has decided

that it is not necessary to prescribe the

content and format for status reports

under § 314.81(b)(2)(viii) and has

removed this requirement. Section

314.81(b)(2)(viii) and (b)(2)(ix) are

retained in this rule due to the

reorganization of § 314.81(b)(2)(vii).

(Comment 10) Two comments

requested that CMC studies be exempt

from inclusion in proposed

§ 314.81(b)(2)(viii) because there is no

purpose in providing such information

in this section. One comment said that

even though current § 314.81(b)(2)(vii)

requires status reports for ‘‘any’’

postmarketing study, existing regulation

and guidance have previously

established a more narrow definition of

the CMC reporting requirement. The

comment explained that current

§ 314.81(b)(2)(iv) states that reports for

CMC changes are only required for new

information that may affect FDA’s

previous conclusions about the safety or

effectiveness of the drug product and

that the guidance for industry on

‘‘Format and Content for the CMC

section of an Annual Report’’ specifies

only the need to include stability data

under current § 314.81(b)(2)(vii). The

comment recommended that CMC study

information be provided under current

§ 314.81(b)(2)(iv) so that all the

information pertinent to the chemistry

review would be consolidated into a

single section. Another comment said

that reporting the status of CMC studies

is not pertinent and repeating this

information under proposed

§ 314.81(b)(2)(viii) is redundant and

unnecessary.

FDA disagrees in part with this

comment. Section 314.81(b)(2)(vii)

currently requires reporting of any

postmarketing study. FDA’s current

guidance for industry states that data

accumulated from ongoing stability

studies should be included in

§ 314.81(b)(2)(vii). Therefore, it is clear

from existing regulations and guidance

that stability studies are to be reported

under existing § 314.81(b)(2)(vii) (now

§ 314.81(b)(2)(viii) of the rule). These

reports provide FDA with valuable

information regarding the safety and

efficacy of products, and FDA has

decided to retain this requirement in the

final rule. However, FDA has decided to

modify § 314.81(b)(2)(viii) to clarify the

reporting requirements for CMC studies.

FDA will maintain a requirement for

reporting data from all ongoing product

stability studies including those that are

being conducted without a

postmarketing study commitment, (e.g.,

annual stability assessment performed

in conformance with 21 CFR 211.166).

For other types of CMC studies, FDA is

revising § 314.81(b)(2)(viii) to require a

status report for only those studies

which the applicant has agreed to

perform. This section now reads as

follows:

Status of other postmarketing studies.

A status report of any postmarketing

study not included under paragraph

(b)(2)(vii) of this section that is being

performed by, or on behalf of, the

applicant. A status report is to be

included for any chemistry,

manufacturing, and controls studies that

the applicant has agreed to perform and

for all product stability studies.

Information from other CMC studies,

experiences, investigations, or tests that

are not stability studies or the subject of

a specific commitment but that provide

new information that may affect FDA’s

previous decisions about product safety

and efficacy will continue to be reported

under § 314.81(b)(2)(iv).

E. Fulfillment of Commitments

FDA proposed at §§ 314.81(b)(2)(vii)

and 601.70(b) that the status of

postmarketing studies be submitted to

the agency annually until FDA notifies

the applicant, in writing, that the agency

concurs with the applicant’s

determination that the study

commitment has been fulfilled or that

the study is either no longer feasible or

would no longer provide useful

information.

(Comment 11) Three comments

requested that FDA specify the

timeframe for agency review of a final

study report and for notifying the

applicant whether or not the

postmarketing study commitment has

been fulfilled or that a commitment is

either no longer feasible to fulfill or

would no longer provide useful

information. One of the comments

suggested a 90-day timeframe and

another comment suggested a 60-day

timeframe.

In general, FDA expects that final

study reports for postmarketing study

commitments will be submitted to the

agency with a supplemental application

to modify a product’s labeling when the

studies support such a change. When

they are submitted in support of a

supplement, FDA will review the

submission under established review

times for supplements. (For Prescription

Drug User Fee Act (PDUFA) products,

see letters from Secretary of Health and

Human Services to the Chairman of the

Committee on Commerce of the House

of Representatives (143 Congressional

Record H10886, November 13, 1997),

and the Chairman of the Committee on

Labor and Human Resources of the

Senate (143 Congressional Record

S12653, November 13, 1997)). If no

supplemental application is submitted

or a supplement is submitted for a

product not covered by PDUFA, FDA

will generally review the final study

report and notify the applicant in

writing within 1 year of receipt of the

report regarding whether it considers

the commitment to have been met.

(Comment 12) One comment said that

the requirement to continue to submit

status reports on terminated

postmarketing studies until FDA

considers that the study commitments

have been fulfilled is too vague. The

comment requested clarification of the

criteria that the agency would use to

deem a study fulfilled.

FDA will review final study reports

and determine whether or not the study

met the objectives of the commitment.

Whether or not the objectives have been

met will have to be determined on a

case-by-case basis because of the variety

of postmarketing study commitments.

Once FDA completes its review of the

final study report, it will notify the

applicant, in writing, of the agency’s

conclusion. An applicant would be

required to submit annual status reports

to FDA until it receives written

notification that the agency concludes

that: (1) The study commitment has

been met, or (2) the study is either no

longer feasible or would no longer

provide useful information.

FDA may conclude that the study is

no longer feasible but that the

commitment’s objectives remain

important and can be addressed through

a study of modified design. In this case,

the original study may be terminated

with no further reporting once a new

postmarketing study commitment and

schedule are agreed upon.

FDA may conclude that even though

a study was completed, it failed to meet

the commitment objectives; or an

applicant may terminate a study that

FDA subsequently determines is feasible

and would yield useful information. In

these cases, the agency may ask the

applicant to undertake another study to

fulfill its commitment.

(Comment 13) One comment said that

FDA’s confirmation in writing that a

study commitment has been fulfilled

could reasonably be accommodated

through addition of a suitable field in

the Form FDA 2252 (Transmittal of

Periodic Reports for Drugs for Human

Use), which would be completed by

FDA at the time that receipt of the

annual report is acknowledged. From

64614 Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations

that point on, the comment said that the

status of the postmarketing commitment

should be tracked under outstanding

regulatory business. The comment noted

that this suggestion, intended to reduce

the administrative burden on FDA of

acknowledging receipt of final study

reports, would not remove the need for

FDA to confirm in writing that they

have evaluated the study report and

concur with the applicant’s conclusions

or proposed action (e.g., submission and

approval of a labeling supplement to

accommodate study results).

FDA disagrees with this suggestion.

The agency will not acknowledge that

the postmarketing study commitment

has been fulfilled until it has reviewed

the final study report and concurs that

the commitment has been met.

Applicants found to have fulfilled their

commitments will be notified in

writing. In addition, this information

will be acknowledged in the agency’s

data bases and website.

F. Annual Report Submission Date

Current § 314.81(b)(2) requires that an

applicant submit an annual report each

year within 60 days of the anniversary

date of U.S. approval of the application.

FDA proposed to require the same

submission times at § 601.70(c) for

annual progress reports of

postmarketing study commitments

entered into by applicants with licensed

biological products.

(Comment 14) One comment said

that, for postmarketing studies that are

already underway and for which annual

reports are already provided, applicants

should be permitted to continue to use

the annual reporting cycles that are

already established. The comment noted

that it submits annual reports based on

the anniversary date of the study

initiation rather than the anniversary

date of U.S. approval.

Current § 314.81(b)(2) requires that

NDA annual reports be submitted to the

agency within 60 days of the

anniversary date of approval of the

application. FDA will continue to

require that NDA annual reports be

submitted within the same timeframe.

Applicants would not be permitted to

submit NDA or BLA annual reports

based on the anniversary date of a

study’s initiation.

Many drug and licensed biological

products have multiple postmarketing

studies underway that were initiated on

different dates. The submission of

annual reports based on the date of

study initiation would result in multiple

reports in any given year, thereby

unnecessarily increasing an applicant’s

reporting burden and complicating

FDA’s tracking and review of

postmarketing study commitment

reports. It is FDA’s intent to minimize

the reporting burden on industry by

requiring only a single annual report for

any NDA, ANDA, or BLA product. This

single report allows applicants to

submit status information on all studies

and allows FDA reviewers to review and

evaluate at one time the progress of all

studies, some of which may be related.

G. Implementation Scheme—Effective

Dates

FDA proposed that any final rule that

may issue based on the proposed rule

become effective 90 days after its date

of publication in the Federal Register.

Applicants that have entered into a

commitment prior to November 21,

1997, to conduct a postmarketing study

under proposed § 314.81(b)(2)(vii) or

§ 601.70 would be required, as

mandated by FDAMA, to submit an

initial report to FDA within 6 months

after the effective date of any final rule

that issued based on the proposed rule.

(Comment 15) One comment

requested that FDA provide that the

effective date of any final rule be 120

days after the date of publication of the

rule in the Federal Register. The

comment noted that, with the proposed

90-day effective date, an applicant could

be required to submit an initial report 5

months following publication of the

final rule, depending on the anniversary

date of their products. The comment

claimed that the 90-day effective date is

not consistent with section 130 of

FDAMA which indicates that applicants

should have 6 months following the

issuance of final regulations to submit

initial reports on postmarketing study

commitments. The comment

recommended that the effective date be

modified to ensure that all applicants

will have at least 6 months to file

reports under the new requirements.

FDA does not believe that section 130

of FDAMA requires the agency to give

a period of 6 months after issuing a final

rule for applicants to prepare a

postmarketing study status report.

Rather, section 130(a) of FDAMA

requires all applicants, regardless of the

anniversary date of the approval of their

drug, to submit status information for

postmarketing study commitments

made prior to November 21, 1997,

within 6 months of the final rule’s

issuance. This timely submission of

information is necessary to allow FDA

to meet its reporting obligation in

providing Congress with an evaluation

of industry’s performance in meeting

postmarketing commitment obligations

and FDA’s performance in reviewing

those postmarketing study reports.

However, FDA has considered the

comment and is revising the effective

date to 120 days after the date of

publication of the rule in the Federal

Register. Although FDA anticipates the

information required to complete an

inital report on the progress of

postmarketing studies is readily

available to the applicant, the agency

understands that some applicants may

have a greater reporting burden than

other applicants due to a larger number

of postmarketing commitments.

Revision of the effective date will give

all applicants a minimum of 4 months

to prepare an initial report on their

postmarketing commitments. If an

applicant chooses to submit the report

up to 60 days after the anniversary date

of the approval of the drug, the

applicant will have 6 months in which

to file an initial report.

Once the rule goes into effect, annual

reports due on or after the effective date

must meet the format and content

requirements of this final rule. An

applicant who has annual reports due

on or after August 27, 2001, will be

required to submit a special 6-month

report for all commitments made prior

to November 21, 1997. This one-time

additional report is required if:

(1) The drug or biological product was

approved before November 21, 1997;

(2) Postmarketing study commitments

were made before November 21, 1997;

and

(3) The next annual report is not due

until August 27, 2001, or later.

(Comment 16) One comment

requested that FDA remove the

requirement to submit a separate initial

report within 6 months of the effective

date of the final rule for pre-FDAMA

commitments. The comment asserted

that these reports would contain data

from a time interval of less than 1 year

and that significant resources would be

required to prepare such a report as well

as for FDA to review the report, which,

due to the limited data, would be of

minimal value. Another comment said

that there is little value in requiring

submission of these separate reports and

that the requirement should be fulfilled

in the next annual report due for each

product. The comment claimed that this

would also be more compatible with

collation and publication of the planned

Annual Federal Register Report.

FDA does not accept this suggestion.

Section 130(a) of FDAMA requires that

an initial report on the progress of

postmarketing commitments made prior

to November 21, 1997, be submitted to

FDA within 6 months of the agency

issuing a final rule. Although some

information on postmarketing studies

may be included in annual reports for

Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64615

new drugs submitted before the effective

date of the final rule, these reports may

not include all information necessary

for FDA to evaluate a study’s progress.

Also, applicants of approved biological

products may not have previously

submitted study status information.

FDA acknowledges that the special 6-

month report may contain limited new

data. However, the submission of that

data, in the format required by

§§ 314.81(b)(2)(vii) and 601.70(b), is

necessary to allow FDA to respond in a

timely manner to Congress as required

in section 130(b) of FDAMA. Therefore,

FDA maintains this one-time reporting

requirement.

IV. 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.

V. Analysis of Impacts

FDA has examined the impact of this

final rule under Executive Order 12866

and the Regulatory Flexibility Act (5

U.S.C. 601–612) (as amended by subtitle

D of the Small Business Regulatory

Fairness Act of 1966 (Public Law 104–

121)), and the Unfunded Mandates

Reform Act of 1995 (Public Law 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). The

Regulatory Flexibility Act requires

agencies to analyze whether a rule may

have a significant impact on a

substantial number of small entities

and, if it does, to analyze regulatory

options that would minimize the

impact. Section 202 of the Unfunded

Mandates Reform Act requires that

agencies prepare a written statement of

anticipated costs and benefits and

before proposing any rule that may

result in an expenditure by State, local,

and tribal governments, in the aggregate,

or by the private sector of $100 million

(adjusted annually for inflation) in any

one year.

The agency has determined that the

final rule is not a significant action as

defined in the Unfunded Mandates

Reform Act, and will not have an effect

on the economy that exceeds $100

million in any one year. The analysis

below details FDA’s estimate of the

potential cost and the potential benefit

of the rule. Based on FDA’s analysis

using available data, the agency does

not anticipate that the rule will result in

a significant impact on a substantial

number of small entities.

A. Nature of Impact

Currently, applicants holding

approved NDA’s or ANDA’s are

required to submit annual reports to the

agency that include information on the

current status of any postmarketing

studies of the drug product performed

by, or on the behalf of, the applicant.

Although the final rule prescribes the

format for the required information, this

requirement would add no new

economic burden for the majority of

NDA and ANDA applicants. About half

of the applicants holding approved

NDA’s or ANDA’s with outstanding

postmarketing study commitments

made prior to the enactment of FDAMA

may incur a small cost the first year, if

their annual report is due within the last

6 months after the effective date of

issuance of the final rule and they must

submit one initial report within the first

6 months after the effective date. FDA

estimates that: (1) There will be

approximately 116 such reports

submitted; (2) each report will report on

two postmarketing studies, on average;

and (3) each report will require about 16

hours (or 8 hours per study) to

complete. Assuming an average wage

rate of $35 per hour, the estimated, onetime cost of this provision is $64,960.

Applicants with licensed biological

products are currently required to

submit information on postmarketing

studies in pediatric populations in

annual reports to the agency. These

applicants will incur additional costs to

comply with the requirements in this

final rule. The agency estimates that

about 33 applicants will submit

postmarketing status reports (reporting

on two postmarketing studies, on

average) on approximately 43 approved

BLA’s annually. As the reporting

requirements are not extensive and the

information is readily accessible to the

applicant, FDA estimates that

establishments will require about 16

hours to complete the required

information for each report (or 8 hours

for each study). Assuming an average

wage rate of $35 per hour, the estimated

incremental cost of the annual reporting

requirement will be $560 per report, for

an industry total of $24,080 per year. As

with applicants holding NDA’s or

ANDA’s, a few applicants with licensed

biological products with outstanding

postmarketing study commitments may

also incur an additional, one-time cost

because they must submit their initial

report within the first 6 months after the

effective date of the final rule and an

annual report within the last 6 months

of the year. FDA estimates there will be

approximately seven such reports, for a

total one-time cost of about $4,000.

B. Small Business Impacts

The requirements in this final rule

will not have a significant economic

impact on a substantial number of small

entities. The agency neither expects the

final rule to result in an increased

number of completed postmarketing

studies nor believes that applicants will

incur significantly increased costs from

completing studies earlier than

intended, as a result of the reporting,

tracking, and disclosure activities

implemented by the agency. Because

affected applicants holding NDA’s and

ANDA’s must currently submit annual

reports to the agency, they already have

procedures in place to monitor their

postmarketing studies. The additional

reporting requirement for applicants

holding approved BLA’s and the

reformatting of the annual reports for

applicants holding NDA’s and ANDA’s

would be minimal. To simplify the

reporting requirement further, however,

the agency will publish a guidance for

industry to aid applicants in preparing

reports in the proper format (see section

I.C of this document).

C. Federalism

FDA has analyzed this final rule in

accordance with the principles set forth

in Executive Order 13132. FDA has

determined that the rule does not

contain policies that have substantial

direct effects on the States, on the

relationship between the National

Government and the States, or on the

distribution of power and

responsibilities among the various

levels of government. Accordingly, the

agency has concluded that the rule does

not contain policies that have

federalism implications as defined in

the order and, consequently, a

federalism summary impact statement is

not required.

VI. The Paperwork Reduction Act of

1995

This final rule contains information

collection provisions that were

reviewed by the Office of Management

and Budget (OMB) under the Paperwork

Reduction Act of 1995 (the PRA) (44

U.S.C. 3501–3520), and that FDA

invited the public to send comments to

OMB. No comments were received by

OMB on these provisions. A description

of these provisions is shown below with

an estimate of the annual reporting

burden. Included in the estimate is the

64616 Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations

time for reviewing the instructions,

searching existing data sources,

gathering and maintaining the data

needed, and completing and reviewing

each collection of information.

Title: Reporting the Status of

Postmarketing Studies for Approved

Human Drugs and Licensed Biological

Products.

Description: Section 506B of the act

provides FDA with additional authority

for monitoring the progress of

postmarketing studies that companies

have made a commitment to conduct

and also requires the agency to make the

status of these studies publicly

available.

Under section 506B(a) of the act,

applicants that have committed to

conduct a postmarketing study for an

approved human drug or biological

product must submit to FDA a report of

the progress of the study or the reasons

for the failure of the applicant to

conduct the study. This report must be

submitted within 1 year after the U.S.

approval of the application and then

annually until the study is completed or

terminated. Under §§ 314.81(b)(2)(vii)

and 601.70(b), information submitted in

a status report would be limited to that

which is needed to sufficiently identify

each applicant that has committed to

conduct a postmarketing study, the

status of the study that is being

reported, and the reasons, if any, for the

applicant’s failure to conduct, complete,

and report the study.

Currently under § 314.81(b)(2),

applicants holding an NDA or an ANDA

must submit status reports on

postmarketing studies for the approved

human drug product as part of an

annual report to FDA. The agency is

amending § 314.81(b)(2)(vii) to specify

information that must be included in

status reports submitted under section

506B of the act (studies of clinical

safety, clinical efficacy, clinical

pharmacology, and nonclinical

toxicology that are required by FDA or

that an applicant commits, in writing, to

conduct either at the time of approval of

an application or a supplement to an

application or after approval of an

application or supplement). New

§ 314.81(b)(2)(viii) of the final rule

requires status information on any

postmarketing study commitments not

reported under paragraph (b)(2)(vii) that

are being performed by, or on behalf of,

the applicant; and paragraph (b)(2)(ix)

permits the applicant to list any open

regulatory business with FDA

concerning the drug product subject to

the application. For licensed biological

products, FDA is requiring applicants

under § 601.70 to submit postmarketing

status reports for studies of clinical

safety, clinical efficacy, clinical

pharmacology, and nonclinical

toxicology that are required by FDA or

that an applicant of a BLA commits to

conduct, in writing, at the time of

approval of an application or a

supplement to an application or after

approval of an application or a

supplement. FDA is revising § 601.28(c)

to require that the status of

postmarketing pediatric studies

described in new § 601.70 be reported

under § 601.70 rather than § 601.28.

This final rule is intended to provide

FDA with specific procedures for

monitoring the progress of

postmarketing studies that companies

have made a commitment, in writing, to

conduct and also to permit the agency

to make the status of these studies

publicly available.

Description of Respondents:

Applicants holding approved

applications for human drugs and

biological products that have committed

to conduct postmarketing studies.

As required by section 3506(c)(2)(B)

of the PRA, FDA provided an

opportunity for public comment on the

information collection requirements of

the proposed rule (64 FR 67207). In

accordance with the PRA, OMB

reserved approval of the information

collection burden in the proposed rule

stating ‘‘FDA shall assess comments

received regarding information

collection requirements contained in the

proposed rule. These comments shall be

addressed in the preamble to the final

rule.’’ No letters of comment on the

information collection requirements

were submitted to OMB.

Under current § 314.81(b)(2),

applicants with approved NDA’s and

ANDA’s for human drugs are required to

submit to the agency two copies of the

annual reports that must include

information on the current status of any

postmarketing study (OMB control No.

0910–0001).

New § 314.81(b)(2)(vii) expressly

requires status information to be

provided in a specific format as part of

the status reports of postmarketing

study commitments (clinical safety,

clinical efficacy, clinical pharmacology,

and nonclinical toxicology), a subpart of

the annual report. Based on past

experience, the agency estimates that

each applicant holding an approved

NDA or ANDA would expend an

additional 8 hours to reformat the

annual report. This is a one-time burden

required under new § 314.81(b)(2)(vii).

Based on the number of drug applicants

in past years who have committed to

conduct postmarketing studies, the

agency estimates that this provision

would apply to approximately 183

applicants and approximately 462

postmarketing studies.

Based upon information obtained

from the Center for Biologics Evaluation

and Research’s computerized

application and license tracking data

base, the agency estimates that

approximately 33 applicants with 43

approved BLA’s have committed to

conduct approximately 86

postmarketing studies (clinical safety,

clinical efficacy, clinical pharmacology,

and nonclinical toxicology) and would

be required to submit an annual

progress report on those postmarketing

studies under § 601.70. Section 601.70

requires postmarketing studies status

reports for the first time for all

biological products. Previously, status

reports were required only for

postmarketing studies in pediatric

populations. Based on past experience

with reporting under § 314.81(b)(2), the

agency estimates that approximately 8

hours annually are required for an

applicant to gather, complete, and

submit the appropriate information for

each study (approximately two studies

per report). Included in these 8 hours is

the time necessary to initially format the

status report.

Applicants holding NDA’s, ANDA’s,

and BLA’s whose anniversary date of

U.S. approval of the application falls

within the latter half of the year after the

effective date of this final rule are

required under section 506B of the act

to submit an initial report to FDA for

postmarketing studies committed to be

conducted prior to November 21, 1997,

within 6 months after the effective date

of the final rule in addition to the

reports required by the final rule. This

information collection is a statutory

requirement for which the final rule

adds no additional burden other than

prescribing the format. The burden of

setting up the format is calculated under

§§ 314.81(b)(2)(vii) and 601.70(b).

Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64617

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN 1

21 CFR Section No. of

Respondents

Annually

Frequency per

Response

Total Annual

Response

Hours per

Response Total Hours

314.81(b)(2)(vii), (b)(2)(viii), and

(b)(2)(ix) 2 183 2.5 462 8 3,696

601.70(b) and (d) 33 2.6 86 8 688

Total 4,384

1There are no capital costs or operating and maintenance costs asociated with this collection of information.

2One-time burden for reformatting annual report.

The information collection

requirements of the final rule have been

submitted to OMB for review. Prior to

the effective date of the final rule, FDA

will publish a document in the Federal

Register announcing OMB’s decision to

approve, modify, or disapprove the

information collection requirements in

the final rule. An agency may not

conduct or sponsor, and a person is not

required to respond to, a collection of

information unless it displays a

currently valid OMB control number.

List of Subjects

21 CFR Part 314

Administrative practice and

procedure, Confidential business

information, Drugs, Reporting and

recordkeeping requirements.

21 CFR Part 601

Administrative practice and

procedure, Biologics, Confidential

business information.

Therefore, under the Federal Food,

Drug, and Cosmetic Act, the Public

Health Service Act, and under authority

delegated to the Commissioner of Food

and Drugs, 21 CFR parts 314 and 601 are

amended as follows:

PART 314—APPLICATIONS FOR FDA

APPROVAL TO MARKET A NEW DRUG

1. 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, 355a, 356, 356a, 356b, 356c, 371,

374, 379e.

2. Section 314.81 is amended by

revising the introductory text of

paragraph (b)(2), by revising paragraph

(b)(2)(vii), and by adding paragraphs

(b)(2)(viii) and (b)(2)(ix) to read as

follows:

§ 314.81 Other postmarketing reports.

* * * * *

(b) * * *

(2)Annual report. The applicant shall

submit each year within 60 days of the

anniversary date of U.S. approval of the

application, two copies of the report to

the FDA division responsible for

reviewing the application. Each annual

report is required to be accompanied by

a completed transmittal Form FDA 2252

(Transmittal of Periodic Reports for

Drugs for Human Use), and must

include all the information required

under this section that the applicant

received or otherwise obtained during

the annual reporting interval that ends

on the U.S. anniversary date. The report

is required to contain in the order listed:

* * * * *

(vii) Status reports of postmarketing

study commitments. A status report of

each postmarketing study of the drug

product concerning clinical safety,

clinical efficacy, clinical pharmacology,

and nonclinical toxicology that is

required by FDA (e.g., accelerated

approval clinical benefit studies,

pediatric studies) or that the applicant

has committed, in writing, to conduct

either at the time of approval of an

application for the drug product or a

supplement to an application, or after

approval of the application or a

supplement. For pediatric studies, the

status report shall include a statement

indicating whether postmarketing

clinical studies in pediatric populations

were required by FDA under § 201.23 of

this chapter. The status of these

postmarketing studies shall be reported

annually until FDA notifies the

applicant, in writing, that the agency

concurs with the applicant’s

determination that the study

commitment has been fulfilled or that

the study is either no longer feasible or

would no longer provide useful

information.

(a) Content of status report. The

following information must be provided

for each postmarketing study reported

under this paragraph:

(1) Applicant’s name.

(2) Product name. Include the

approved drug product’s established

name and proprietary name, if any.

(3) NDA, ANDA, and supplement

number.

(4) Date of U.S. approval of NDA or

ANDA.

(5) Date of postmarketing study

commitment.

(6) Description of postmarketing study

commitment. The description must

include sufficient information to

uniquely describe the study. This

information may include the purpose of

the study, the type of study, the patient

population addressed by the study and

the indication(s) and dosage(s) that are

to be studied.

(7) Schedule for completion and

reporting of the postmarketing study

commitment. The schedule should

include the actual or projected dates for

submission of the study protocol to

FDA, completion of patient accrual or

initiation of an animal study,

completion of the study, submission of

the final study report to FDA, and any

additional milestones or submissions for

which projected dates were specified as

part of the commitment. In addition, it

should include a revised schedule, as

appropriate. If the schedule has been

previously revised, provide both the

original schedule and the most recent,

previously submitted revision.

(8) Current status of the

postmarketing study commitment. The

status of each postmarketing study

should be categorized using one of the

following terms that describes the

study’s status on the anniversary date of

U.S. approval of the application or other

agreed upon date:

(i) Pending. The study has not been

initiated, but does not meet the criterion

for delayed.

(ii) Ongoing. The study is proceeding

according to or ahead of the original

schedule described under paragraph

(b)(2)(vii)(a)(7) of this section.

(iii) Delayed. The study is behind the

original schedule described under

paragraph (b)(2)(vii)(a)(7) of this section.

(iv) Terminated. The study was ended

before completion but a final study

report has not been submitted to FDA.

(v) Submitted. The study has been

completed or terminated and a final

study report has been submitted to FDA.

64618 Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations

(9) Explanation of the study’s status.

Provide a brief description of the status

of the study, including the patient

accrual rate (expressed by providing the

number of patients or subjects enrolled

to date, and the total planned

enrollment), and an explanation of the

study’s status identified under

paragraph (b)(2)(vii)(a)(8) of this section.

If the study has been completed, include

the date the study was completed and

the date the final study report was

submitted to FDA, as applicable.

Provide a revised schedule, as well as

the reason(s) for the revision, if the

schedule under paragraph

(b)(2)(vii)(a)(7) of this section has

changed since the last report.

(b) Public disclosure of information.

Except for the information described in

this paragraph, FDA may publicly

disclose any information described in

paragraph (b)(2)(vii) of this section,

concerning a postmarketing study, if the

agency determines that the information

is necessary to identify the applicant or

to establish the status of the study,

including the reasons, if any, for failure

to conduct, complete, and report the

study. Under this section, FDA will not

publicly disclose trade secrets, as

defined in § 20.61 of this chapter, or

information, described in § 20.63 of this

chapter, the disclosure of which would

constitute an unwarranted invasion of

personal privacy.

(viii) Status of other postmarketing

studies. A status report of any

postmarketing study not included under

paragraph (b)(2)(vii) of this section that

is being performed by, or on behalf of,

the applicant. A status report is to be

included for any chemistry,

manufacturing, and controls studies that

the applicant has agreed to perform and

for all product stability studies.

(ix) Log of outstanding regulatory

business. To facilitate communications

between FDA and the applicant, the

report may, at the applicant’s discretion,

also contain a list of any open regulatory

business with FDA concerning the drug

product subject to the application (e.g.,

a list of the applicant’s unanswered

correspondence with the agency, a list

of the agency’s unanswered

correspondence with the applicant).

PART 601—LICENSING

3. The authority citation for 21 CFR

part 601 is revised to read as follows:

Authority: 15 U.S.C. 1451–1561; 21 U.S.C.

321, 351, 352, 353, 355, 356b, 360, 360c–

360f, 360h–360j, 371, 374, 379e, 381; 42

U.S.C. 216, 241, 262, 263, 264; sec 122, Pub.

L. 105–115, 111 Stat. 2322 (21 U.S.C. 355

note).

4. Section 601.28 is amended by

revising the second sentence in

paragraph (c) to read as follows:

§ 601.28 Annual reports of postmarketing

pediatric studies.

* * * * *

(c) * * * The statement shall include

whether postmarketing clinical studies

in pediatric populations were required

or agreed to, and, if so, the status of

these studies shall be reported to FDA

in annual progress reports of

postmarketing studies under § 601.70

rather than under this section.

5. Subpart G, consisting of § 601.70, is

added to part 601 to read as follows:

Subpart G—Postmarketing Studies

§ 601.70 Annual progress reports of

postmarketing studies.

(a) General requirements. This section

applies to all required postmarketing

studies (e.g., accelerated approval

clinical benefit studies, pediatric

studies) and postmarketing studies that

an applicant has committed, in writing,

to conduct either at the time of approval

of an application or a supplement to an

application, or after approval of an

application or a supplement.

Postmarketing studies within the

meaning of this section are those that

concern:

(1) Clinical safety;

(2) Clinical efficacy;

(3) Clinical pharmacology; and

(4) Nonclinical toxicology.

(b)What to report. Each applicant of a

licensed biological product shall submit

a report to FDA on the status of

postmarketing studies for each approved

product application. The status of these

postmarketing studies shall be reported

annually until FDA notifies the

applicant, in writing, that the agency

concurs with the applicant’s

determination that the study

commitment has been fulfilled, or that

the study is either no longer feasible or

would no longer provide useful

information. Each annual progress

report shall be accompanied by a

completed transmittal Form FDA–2252,

and shall include all the information

required under this section that the

applicant received or otherwise

obtained during the annual reporting

interval which ends on the U.S.

anniversary date. The report must

provide the following information for

each postmarketing study:

(1) Applicant’s name.

(2) Product name. Include the

approved product’s proper name and

the proprietary name, if any.

(3) Biologics license application (BLA)

and supplement number.

(4) Date of U.S. approval of BLA.

(5) Date of postmarketing study

commitment.

(6) Description of postmarketing study

commitment. The description must

include sufficient information to

uniquely describe the study. This

information may include the purpose of

the study, the type of study, the patient

population addressed by the study and

the indication(s) and dosage(s) that are

to be studied.

(7) Schedule for completion and

reporting of the postmarketing study

commitment. The schedule should

include the actual or projected dates for

submission of the study protocol to

FDA, completion of patient accrual or

initiation of an animal study,

completion of the study, submission of

the final study report to FDA, and any

additional milestones or submissions for

which projected dates were specified as

part of the commitment. In addition, it

should include a revised schedule, as

appropriate. If the schedule has been

previously revised, provide both the

original schedule and the most recent,

previously submitted revision.

(8) Current status of the

postmarketing study commitment. The

status of each postmarketing study

should be categorized using one of the

following terms that describes the

study’s status on the anniversary date of

U.S. approval of the application or other

agreed upon date:

(i) Pending. The study has not been

initiated, but does not meet the criterion

for delayed.

(ii) Ongoing. The study is proceeding

according to or ahead of the original

schedule described under paragraph

(b)(7) of this section.

(iii) Delayed. The study is behind the

original schedule described under

paragraph (b)(7) of this section.

(iv) Terminated. The study was ended

before completion but a final study

report has not been submitted to FDA.

(v) Submitted. The study has been

completed or terminated and a final

study report has been submitted to FDA.

(9) Explanation of the study’s status.

Provide a brief description of the status

of the study, including the patient

accrual rate (expressed by providing the

number of patients or subjects enrolled

to date, and the total planned

enrollment), and an explanation of the

study’s status identified under

paragraph (b)(8) of this section. If the

study has been completed, include the

date the study was completed and the

date the final study report was

submitted to FDA, as applicable.

Provide a revised schedule, as well as

the reason(s) for the revision, if the

schedule under paragraph (b)(7) of this

Federal Register / Vol. 65, No. 210 / Monday, October 30, 2000 / Rules and Regulations 64619

section has changed since the previous

report.

(c) When to report. Annual progress

reports for postmarketing study

commitments entered into by applicants

shall be reported to FDA within 60 days

of the anniversary date of the U.S.

approval of the application for the

product.

(d) Where to report. Submit two

copies of the annual progress report of

postmarketing studies to the Food and

Drug Administration, Center for

Biologics Evaluations and Research,

Document Control Center (HFM–99),

1401 Rockville Pike, Rockville, MD

20852–1448.

(e) Public disclosure of information.

Except for the information described in

this paragraph, FDA may publicly

disclose any information concerning a

postmarketing study, within the

meaning of this section, if the agency

determines that the information is

necessary to identify an applicant or to

establish the status of the study

including the reasons, if any, for failure

to conduct, complete, and report the

study. Under this section, FDA will not

publicly disclose trade secrets, as

defined in § 20.61 of this chapter, or

information, described in § 20.63 of this

chapter, the disclosure of which would

constitute an unwarranted invasion of

personal privacy.

Dated: October 13, 2000.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 00–27731 Filed 10–26–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. 94N–0380]

Gastroenterology and Urology

Devices; Effective Date of the

Requirement for Premarket Approval

of the Implanted Mechanical/Hydraulic

Urinary Continence Device; Correction

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule; correction.

SUMMARY: The Food and Drug

Administration (FDA) is correcting a

final rule that appeared in the Federal

Register of September 26, 2000 (65 FR

57726). The final rule requires the filing

of a premarket approval application or

a notice of completion of a product

development protocol for the implanted

mechanical/hydraulic urinary

continence device, a generic type of

medical device intended for the

treatment of urinary incontinence. In

the final rule, the effective date was

stated incorrectly. This document

corrects that error.

FOR FURTHER INFORMATION CONTACT:

Nicole L. Wolanski, Center for Devices

and Radiological Health (HFZ–470),

Food and Drug Administration, 9200

Corporate Blvd., Rockville, MD 20850,

301–594–2194.

SUPPLEMENTARY INFORMATION: In FR Doc.

00–24632 appearing on page 57726 in

the Federal Register of September 26,

2000, the following correction is made:

1. On page 57726, in the second

column, under the EFFECTIVE DATE

caption, the date ‘‘October 26, 2000’’ is

corrected to read ‘‘September 26, 2000.’’

Dated: October 19, 2000.

Linda S. Kahan,

Deputy Director for Regulations Policy, Center

for Devices and Radiological Health.

[FR Doc. 00–27736 Filed 10–27–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF DEFENSE

Department of the Air Force

32 CFR Part 811

RIN 0701–AA62

Release, Dissemination, and Sale of

Visual Information Materials

AGENCY: Department of the Air Force,

DoD.

ACTION: Final rule.

SUMMARY: The Department of the Air

Force is revising our rules on the

Release, Dissemination, and Sale of

Visual Information Materials to reflect

current polices. These rules implement

Air Force Instruction (AFI) 33–117,

Visual Information Management, and

apply to all Air Force activities.

EFFECTIVE DATE: December 1, 2000.

ADDRESSES: Mr. Raymond Dabney, HQ

AFCIC/ITSM, 1250 Air Force Pentagon,

Washington, DC 20330–1250, 703–588–

6136.

FOR FURTHER INFORMATION CONTACT: Mr.

Raymond Dabney, HQ AFCIC/ITSM,

703–588–6136.

SUPPLEMENTARY INFORMATION: The

Department of the Air Force is revising

our rules on the Release, Dissemination,

and Sale of Visual Information Materials

of the Code of Federal Regulations

(CFRs) (32 CFR part 811) to reflect

current policies. This part implements

Air Force Instruction (AFI) 33–117,

Visual Information Management, and

apply to all Air Force activities. This

part was published as a proposed rule

in the Federal Register on December 28,

1999 (64 FR 72621, FR Doc. 99–33604).

Comments were solicited for 60 days

ending on February 28, 2000. No

comments were received.

List of Subjects in 32 CFR Part 811

Archives and records, Motion

pictures.

For the reasons stated in the

preamble, the Department of the Air

Force is revising 32 CFR Part 811 to read

as follows:

PART 811—RELEASE,

DISSEMINATION, AND SALE OF

VISUAL INFORMATION MATERIALS

Sec.

811.1 Exceptions.

811.2 Release of visual information

materials.

811.3 Official requests for visual

information productions or materials.

811.4 Selling visual information materials.

811.5 Customers exempt from fees.

811.6 Visual information product/material

loans.

811.7 Collecting and controlling fees.

811.8 Forms prescribed and availability of

publications.

Authority: 10 U.S.C. 8013.

§ 811.1 Exceptions.

The regulations in this part do not

apply to:

(a) Visual information (VI) materials

made for the Air Force Office of Special

Investigations for use in an investigation

or a counterintelligence report. (See Air

Force Instruction (AFI) 90–301, The

Inspector General Complaints, which

describes who may use these materials.)

(b) VI materials made during Air

Force investigations of aircraft or

missile mishaps according to AFI 91–

204, Safety Investigations and Reports.

(See AFI 90–301.)

§ 811.2 Release of visual information

materials.

(a) Only the Secretary of the Air Force

for Public Affairs (SAF/PA) clears and

releases Air Force materials for use

outside Department of Defense (DoD),

according to AFI 35–205, Air Force

Security and Policy Review Program.

(b) The Secretary of the Air Force for

Legislative Liaison (SAF/LL) arranges

the release of VI material through SAF/

PA when a member of Congress asks for

them for official use.

(c) The International Affairs Division

(HQ USAF/CVAII) or, in some cases, the

major command (MAJCOM) Foreign

Disclosure Office, must authorize

release of classified and unclassified