Federal Register / Vol. 80, No. 43 / Thursday, March 5, 2015 / Notices 11995 

Date: March 31, 2015. 

Time: 8:00 a.m. to 9:00 p.m. 

Agenda: To review and evaluate 

cooperative agreement applications. 

Place: Residence Inn Washington DC, 1199 

Vermont Avenue NW., Washington, DC 

20005. 

Contact Person: Kenneth Ryan, Ph.D., 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 3218, 

MSC 7717, Bethesda, MD 20892, 301–435– 

0229, kenneth.ryan@nih.hhs.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Member 

Conflict: Pregnancy/Neonatology Research. 

Date: March 31, 2015. 

Time: 9:00 a.m. to 5:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892, 

(Virtual Meeting). 

Contact Person: Gary Hunnicutt, Ph.D., 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 6164, 

MSC 7892, Bethesda, MD 20892, 301–435– 

0229, gary.hunnicutt@nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Small 

Business: Innovative Molecular Analysis 

Technology. 

Date: March 31, 2015. 

Time: 1:00 p.m. to 5:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892, 

(Telephone Conference Call). 

Contact Person: Zhang-Zhi Hu, MD, 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 6186, 

MSC 7804, Bethesda, MD 20892, (301) 594– 

2414, huzhuang@csr.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Member 

Conflict: Cancer Therapeutics. 

Date: March 31, 2015. 

Time: 1:00 p.m. to 4:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892, 

(Telephone Conference Call). 

Contact Person: Careen K. Tang-Toth, 

Ph.D., Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 6214, 

MSC 7804, Bethesda, MD 20892, (301) 435– 

3504, tothct@csr.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Member 

Conflict: Organelles’ Dysfunction in 

Neurodegerative Disorders. 

Date: March 31, 2015. 

Time: 4:00 p.m. to 6:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892, 

(Telephone Conference Call). 

Contact Person: Alessandra C. Rovescalli, 

Scientific Review Officer, National Institutes 

of Health, Center for Scientific Review, 6701 

Rockledge Drive, Rm 5205, MSC 7846, 

Bethesda, MD 20892, (301) 435–1021, 

rovescaa@mail.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; ‘‘Program 

Project: BTRC Center Review’’. 

Date: March 31–April 2, 2015. 

Time: 6:00 p.m. to 5:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: Bethesda Marriott Suites, 6711 

Democracy Boulevard, Bethesda, MD 20817. 

Contact Person: Craig Giroux, Ph.D., 

Scientific Review Officer, BST IRG, Center 

for Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 5150, 

Bethesda, MD 20892, 301–435–2204, 

girouxcn@csr.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; RFA–RM– 

14–015: Facile Methods and Technologies for 

Synthesis of Biomedically Relevant 

Carbohydrates. 

Date: March 31, 2015. 

Time: 12:00 p.m. to 6:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892. 

Contact Person: Kathryn M. Koeller, Ph.D., 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 4166, 

MSC 7806, Bethesda, MD 20892, 301–435– 

2681, koellerk@csr.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.306, Comparative Medicine; 

93.333, Clinical Research, 93.306, 93.333, 

93.337, 93.393–93.396, 93.837–93.844, 

93.846–93.878, 93.892, 93.893, National 

Institutes of Health, HHS) 

Dated: February 27, 2015. 

Anna Snouffer, 

Deputy Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2015–05008 Filed 3–4–15; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–N–0299] 

Douglas M. Hargrave; Denial of 

Hearing; Final Debarment Order 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is denying a 

request for a hearing submitted by Dr. 

Douglas M. Hargrave (Dr. Hargrave), and 

is issuing an order under the Federal 

Food, Drug, and Cosmetic Act (the 

FD&C Act) debarring Dr. Hargrave for 2 

years from providing services in any 

capacity to a person that has an 

approved or pending drug product 

application. FDA bases this order on a 

finding that Dr. Hargrave was convicted 

of a misdemeanor under Federal law for 

conduct relating to the regulation of a 

drug product under the FD&C Act and 

that the type of conduct underlying the 

conviction undermines the process for 

the regulation of drugs. In determining 

the appropriateness and period of Dr. 

Hargrave’s debarment, FDA has 

considered the relevant factors listed in 

the FD&C Act. Dr. Hargrave has failed to 

file with the Agency information and 

analyses sufficient to create a basis for 

a hearing concerning this action. 

DATES: The order is effective March 5, 

2015. 

ADDRESSES: Submit applications for 

termination of debarment to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, Rm. 1061, Rockville, 

MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Nathan Doty, Office of Scientific 

Integrity, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Silver Spring, MD 20993, 301– 

796–8556. 

SUPPLEMENTARY INFORMATION: 

I. Background 

On August 11, 2009, in the U.S. 

District Court for the Northern District 

of New York, Dr. Hargrave, a physician, 

pled guilty to a misdemeanor under the 

FD&C Act, namely misbranding a drug 

in violation of sections 301(k), 502(i)(3) 

and 303(a)(1) of the FD&C Act (21 U.S.C. 

331(k), 352(i)(3), 333(a)(1)) and 18 

U.S.C. 2. The basis for this conviction 

was conduct surrounding his injection 

of patients seeking treatment with 

BOTOX/BOTOX Cosmetic (BOTOX) 

with a product, TRI-toxin, distributed 

by Toxin Research International, Inc. 

BOTOX is a biological product derived 

from Botulinum Toxin Type A that is 

manufactured by Allergan, Inc., and was 

approved by FDA for use on humans for 

the treatment of facial wrinkles in 1991. 

According to the records of the criminal 

proceedings, Dr. Hargrave’s colleague in 

the same medical practice, The Plastic 

Surgery Group (TPSG), directed a nurse 

to obtain 31 vials of TRI-toxin, an 

unapproved drug product, which was 

represented by its distributor as 

‘‘Botulinum Toxin Type A.’’ Dr. 

Hargrave then proceeded to inject 

approximately 25 patients, who 

believed they were being injected with 

BOTOX, with TRI-toxin as a substitute. 

Dr. Hargrave is subject to debarment 

based on a finding, under section 

306(b)(2)(B)(i)(I) of the FD&C Act (21 

U.S.C. 335a(b)(2)(B)(i)(I)): (1) That he 

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11996 Federal Register / Vol. 80, No. 43 / Thursday, March 5, 2015 / Notices 

was convicted of a misdemeanor under 

Federal law relating to the regulation of 

a drug product under the FD&C Act and 

(2) that the type of conduct underlying 

the conviction undermines the process 

for the regulation of drugs. By notice to 

Dr. Hargrave dated November 30, 2010, 

FDA’s Office of Regulatory Affairs 

(ORA) proposed to debar him for 4 years 

from providing services in any capacity 

to a person having an approved or 

pending drug product application. 

In a letter dated December 30, 2010, 

through counsel, Dr. Hargrave requested 

a hearing on the proposal. In his request 

for a hearing, Dr. Hargrave 

acknowledges his conviction under 

Federal law, as alleged by FDA. By letter 

dated January 28, 2011, Dr. Hargrave 

submitted materials and arguments in 

support of his request. Dr. Hargrave 

acknowledges that he was convicted of 

a Federal misdemeanor, as found in the 

proposal to debar, but argues that he 

should not be debarred for reasons 

related to the factual basis set forth in 

the proposal to debar. In particular, with 

respect to the considerations for 

determining the appropriateness and 

period of debarment under section 

306(c)(3) of the FD&C Act, he argues 

that there are genuine and substantial 

issues of fact for resolution at a hearing, 

namely factual issues bearing on 

whether he participated in or even knew 

of certain conduct that resulted in his 

violation of the FD&C Act. 

Hearings are granted only if there is 

a genuine and substantial issue of fact. 

Hearings will not be granted on issues 

of policy or law, on mere allegations, 

denials, or general descriptions of 

positions and contentions, or on data 

and information insufficient to justify 

the factual determination urged or the 

action requested (see 21 CFR 12.24(b)). 

The Chief Scientist has considered Dr. 

Hargrave’s arguments, as well as the 

proposal to debar itself, and concludes 

that, although Dr. Hargrave has failed to 

raise a genuine and substantial issue of 

fact requiring a hearing, the appropriate 

period of debarment is 2 years. 

II. Arguments 

In support of his hearing request, Dr. 

Hargrave first asserts that he is not 

subject to debarment under section 

306(b)(2)(B)(i)(I) of the FD&C Act. He 

contends that he pled guilty to a 

misdemeanor violation of the FD&C Act 

(see section 303(a)(1) of the FD&C Act), 

which is a strict liability offense, and 

that thus there was no demonstration or 

admission of criminal intent or 

knowledge underlying the conviction. 

Dr. Hargrave concludes, therefore, that 

the conduct underlying his conviction 

did not undermine the process for the 

regulation of drugs. 

Section 306(b)(2)(B)(i)(I) of the FD&C 

Act specifically provides for the 

debarment of individuals convicted of 

Federal misdemeanors related to the 

regulation of drug products under the 

FD&C Act. Given that misdemeanor 

violations of the FD&C Act themselves 

are strict liability offenses, it stands to 

reason that criminal intent is not a 

critical component to debar an 

individual under section 

306(b)(2)(B)(i)(I). During his criminal 

proceedings, Dr. Hargrave pled guilty to 

misbranding and causing the 

misbranding of a drug in violation of 

sections 301(k), 502(i)(3) and 303(a)(1) 

of the FD&C Act by offering an 

unapproved drug, TRI-toxin, for sale as 

an approved drug product, BOTOX. Dr. 

Hargrave’s conduct undermined the 

process for the regulation of drugs in 

that it permitted an unapproved drug to 

be substituted for an approved drug 

without the knowledge of the patient. 

As a result, Dr. Hargrave is, in fact, 

subject to debarment under section 

306(b)(2)(B)(i)(I) of the FD&C Act. 

Dr. Hargrave next challenges the 

manner in which ORA applied the 

considerations under section 306(c)(3) 

of the FD&C Act in determining the 

appropriateness and period of his 

debarment. In the proposal to debar Dr. 

Hargrave, ORA stated that there are four 

applicable considerations under section 

306(c)(3) of the FD&C Act: (1) The 

nature and seriousness of his offense 

under section 306(c)(3)(A); (2) the 

nature and extent of management 

participation in the offense under 

section 306(c)(3)(B); (3) the nature and 

extent of voluntary steps taken to 

mitigate the impact on the public under 

section 306(c)(3)(C); and (4) prior 

convictions involving matters within 

the jurisdiction of FDA under section 

306(c)(3)(F). ORA found with respect to 

Dr. Hargrave that the first two 

considerations weigh in favor of 

debarment and noted that the third and 

fourth considerations would be treated 

as favorable factors for him. In making 

all of its findings under section 306(c)(3) 

FD&C Act, ORA characterized Dr. 

Hargrave’s conduct based on records 

from his criminal proceedings. 

Under section 306(c)(3)(A) of the 

FD&C Act, in determining the 

appropriateness and period of 

debarment, FDA considers ‘‘the nature 

and seriousness of the offense 

involved.’’ In the proposal to debar, 

ORA relied on the criminal information 

to which Dr. Hargrave pled guilty to 

find that the conduct underlying his 

convictions: 

created a risk of injury to consumers due to 

the use of an unapproved drug, undermined 

[FDA’s] oversight of an approved drug 

product by representing that [he] used the 

approved drug while actually substituting an 

unapproved drug in its place, and seriously 

undermined the integrity of [FDA’s] 

regulation of drug products. 

Under section 306(c)(3)(B) of the FD&C 

Act, ORA also considered the ‘‘nature 

and extent of [Dr. Hargrave’s] 

management participation in the 

offense’’ and specifically found that he 

was a corporate principal who ‘‘pleaded 

guilty to misbranding TRI-toxin’’ and 

‘‘participated in the [TPSG’s] unlawful 

conduct of administering [an] 

unapproved drug on multiple occasions 

to patients.’’ ORA concluded, therefore, 

that the nature and seriousness of Dr. 

Hargrave’s offenses and the nature and 

extent of management participation 

were unfavorable factors with respect to 

him. 

Dr. Hargrave counters ORA’s findings 

with respect to those two considerations 

in section 306(c)(3) of the FD&C Act 

with the following arguments: (1) That 

he did not admit any criminal intent or 

intentional wrongdoing when he pled 

guilty to a misdemeanor offense under 

the FD&C Act; (2) that, in fact, another 

physician at TPSG took unilateral action 

in ordering the TRI-toxin and directing 

a nurse to substitute it for BOTOX; (3) 

that the TRI-toxin vials that they used 

for injecting patients with TRI-toxin 

were identical to the vials he used for 

BOTOX before the substitution; and (4) 

that since the conviction for the 

underlying misdemeanor was of an 

individual, that there was no 

management participation and that, 

thus, the nature and extent of 

management participation is 

inapplicable as a factor in determining 

appropriateness and period of 

debarment. Dr. Hargrave concedes that 

he pled guilty to the misdemeanor 

offense because he was, in fact, guilty of 

offering TRI-toxin for sale to their 

patients as BOTOX. He argues, however, 

that the criminal records do not 

establish any intent or knowledge on his 

part and that thus the conduct 

underlying his conviction does not 

warrant debarment in light of the 

considerations in section 306(c)(3) of 

the FD&C Act. 

As noted previously, ORA relied on 

the records of Dr. Hargrave’s criminal 

proceedings for its findings in the 

proposal to debar. There is nothing 

definitive in the criminal records before 

FDA to contradict Dr. Hargrave’s 

assertions with respect to the nature of 

his involvement in the misdemeanor 

offense to which he pled guilty. The 

criminal information to which Dr. 

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Federal Register / Vol. 80, No. 43 / Thursday, March 5, 2015 / Notices 11997 

1See United States v. Park, 421 U.S. 658, 673– 

74 (1975) (holding that a high-level manager within 

a business entity bears a responsibility to prevent 

and correct violations of the FD&C Act). 

Hargrave pled guilty alleges that TPSG, 

as opposed to Dr. Hargrave, began 

ordering TRI-toxin for use in the 

medical practice, and there are no 

allegations that Dr. Hargrave took part in 

the ordering process. Indeed, the 

proposal to debar states that, as claimed 

by Dr. Hargrave, another physician in 

the practice, William F. DeLuca, Jr., was 

responsible for authorizing a nurse to 

substitute TRI-toxin for BOTOX, not Dr. 

Hargrave. At Dr. Hargrave’s sentencing 

hearing, at which six other 

codefendants, including DeLuca, were 

also sentenced, the presiding judge also 

made clear that he believed DeLuca was 

the physician responsible for making 

the ‘‘mistake’’ that led to the other 

physician’s offenses. In addressing 

DeLuca, the court stated: 

And we’re here because of your actions 

and inactions. As I said, your mistakes were 

different in kind and degree from those of 

your colleagues. It was you who brought this 

drug into the practice, and it was your 

conduct and your failure to check out either 

the company or the drug that you were 

ordering, as you should have done, your 

negligence in doing that that has brought us 

here today in the end. 

In addressing one of the other three 

physicians who pled guilty under 

circumstances similar to Dr. Hargrave’s, 

the court further stated: ‘‘There have 

been disputes on how in the past over 

who knew what and at what point in 

time. It is clear from the facts in this 

case that you had no knowledge that the 

substance was anything other than 

[BOTOX] until your discovery of it in 

November of 2004.’’ 

In short, consistent with the proposal 

to debar Dr. Hargrave for 4 years, the 

records of his criminal proceedings 

establish that the misdemeanor 

convictions for the physicians in TPSG 

other than DeLuca were not based on 

any affirmative involvement in ordering 

the TRI-toxin or substituting the TRItoxin for BOTOX. Furthermore, in 

proposing to debar Dr. Hargrave for 4 

years, ORA did not rely on any findings 

with respect to Dr. Hargrave’s intent or 

knowledge. Rather, citing the records of 

Dr. Hargrave’s criminal proceedings, the 

proposal to debar simply rests on Dr. 

Hargrave’s position of authority within 

TPSG and his conduct in misbranding 

TRI-toxin by administering it to patients 

who believed they were receiving 

BOTOX. As a result, under § 12.24(b), 

there is no genuine and substantial issue 

of fact raised by Dr. Hargrave’s 

arguments for resolution at a hearing. 

As set forth in the proposal to debar 

and summarized previously, Dr. 

Hargrave pled guilty to a misdemeanor 

under the FD&C Act for his role in 

offering a drug under the name of 

another. Based on the undisputed 

record before the Agency, the 

consideration in section 306(c)(3)(A) of 

the FD&C Act with respect to the nature 

and seriousness of the offense involved 

is a favorable factor. As reflected in the 

records of the criminal proceedings, Dr. 

Hargrave’s offense did not rest on any 

intent or knowledge of wrongdoing on 

his part, nor may such intent or 

knowledge be inferred from the 

circumstances of his offense or the 

findings in the proposal to debar. 

Although, as a practicing physician, Dr. 

Hargrave should be expected to take the 

appropriate steps to avoid administering 

an unapproved new drug to patients or 

misrepresenting the drug being 

administered, his failure to do so over 

a t10-month period does not warrant 

considering the nature and seriousness 

of his offense as an unfavorable factor, 

relative to the range of conduct that 

might underlie a Federal misdemeanor 

conviction. 

On the other hand, because of Dr. 

Hargrave’s position of authority within 

TPSG and, thus, presumed ability to 

prevent the series of events that resulted 

in the offense underlying his 

misdemeanor conviction, the nature and 

extent of management participation in 

the offense is an unfavorable factor, for 

the purposes of the consideration under 

306(c)(3)(B) of the FD&C Act. Dr. 

Hargrave asserts that there was no 

management participation, and that, 

thus, this factor is inapplicable because 

the underlying conviction was of an 

individual. However, the criminal 

information to which Dr. Hargrave pled 

guilty alleges that TPSG began ordering 

TRI-toxin for use in the medical 

practice. It is undisputed that Dr. 

Hargrave is a principal in TPSG, and 

this is the basis for considering the 

nature and extent of management 

participation as a factor in determining 

the appropriateness and period of 

debarment. FDA has relied on this factor 

in other debarment cases where the 

underlying conviction was of an 

individual (see 78 FR 68455 (November 

14, 2013), 77 FR 27236–01 (May 9, 

2012)). 

The limited scope of his direct actions 

in committing the underlying 

misdemeanor offense does not mitigate 

the extent of his management 

participation, as established during his 

criminal proceedings and as set out in 

the proposal to debar. It is true that 

nothing in the criminal proceedings or 

the proposal to debar reflects any 

involvement by him in the decision to 

order the TRI-toxin and substitute it for 

BOTOX, and the proposal to debar 

specifically finds that another physician 

authorized a nurse to place that order. 

However, Dr. Hargrave, as a principal of 

TPSG, was responsible for failing to 

ensure that there were controls and 

procedures in place to prevent other 

physicians or a nurse from ordering 

unapproved drugs for administration to 

patients. His own admitted inaction on 

that front warrants treating his 

management participation as an 

unfavorable factor.1

Consistent with the proposal to debar, 

the record establishes that the medical 

practice of which Dr. Hargrave was a 

part ultimately took voluntary steps to 

mitigate the effect on the public health 

from its unlawful conduct (see section 

306(c)(3)(C) of the FD&C Act). 

Furthermore, it is undisputed that Dr. 

Hargrave had no previous criminal 

convictions related to matters within the 

jurisdiction of FDA (see section 

306(c)(3)(F) of the FD&C Act). Therefore, 

these will be treated as favorable factors. 

In light of the foregoing four 

considerations, one of which weighs 

against Dr. Hargrave, debarment for 2 

years is appropriate. 

III. Findings and Order 

Therefore, the Chief Scientist, under 

section 306(b)(2)(B)(i)(I) of the FD&C 

Act and under authority delegated to 

him, finds that Dr. Hargrave has been 

convicted of a misdemeanor under 

Federal law for conduct relating to the 

development or approval of a drug 

product or otherwise relating to the 

regulation of a drug product under the 

FD&C Act and that the conduct 

underlying the conviction undermines 

the regulation of drugs. FDA has 

considered the relevant factors listed in 

section 306(c)(3) of the FD&C Act and 

determined that a debarment of 2 years 

is appropriate. 

As a result of the foregoing findings, 

Dr. Hargrave is debarred for 2 years from 

providing services in any capacity to a 

person with an approved or pending 

drug product application under section 

505, 512, or 802 of the FD&C Act (21 

U.S.C. 355, 360b, or 382), or under 

section 351 of the Public Health Service 

Act (42 U.S.C. 262), effective (see 

DATES), (see 21 U.S.C. 335a(c)(1)(B) and 

(c)(2)(A)(iii) and 21 U.S.C. 321(dd)). 

Any person with an approved, or 

pending, drug product application, who 

knowingly uses the services of Dr. 

Hargrave, in any capacity during his 

period of debarment, will be subject to 

civil money penalties. If Dr. Hargrave, 

during his period of debarment, 

provides services in any capacity to a 

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11998 Federal Register / Vol. 80, No. 43 / Thursday, March 5, 2015 / Notices 

person with an approved or pending 

drug product application he will be 

subject to civil money penalties. In 

addition, FDA will not accept or review 

any abbreviated new drug applications 

submitted by or with the assistance of 

Dr. Hargrave during his period of 

debarment. 

Any application by Dr. Hargrave for 

termination of debarment under section 

306(d) of the FD&C Act should be 

identified with Docket No. FDA–2010– 

N–0299 and sent to the Division of 

Dockets Management (see ADDRESSES). 

All such submissions are to be filed in 

four copies. The public availability of 

information in these submissions is 

governed by 21 CFR 10.20(j). Publicly 

available submissions may be seen in 

the Division of Dockets Management 

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

through Friday. Persons with access to 

the Internet may obtain documents in 

the Docket at http://

www.regulations.gov/. 

Dated: February 24, 2015. 

Stephen Ostroff, 

Director, Office of the Chief Scientist. 

[FR Doc. 2015–05046 Filed 3–4–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–D–0586] 

Clinical Trial Imaging Endpoint 

Process Standards; Draft Guidance for 

Industry; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance for 

industry entitled ‘‘Clinical Trial Imaging 

Endpoint Process Standards.’’ This 

guidance assists sponsors in optimizing 

the quality of imaging data obtained in 

clinical trials intended to support 

approval of drugs and biological 

products. This guidance focuses on 

imaging acquisition, display, archiving, 

and interpretation process standards 

that FDA regards as important when 

imaging is used to assess a trial’s 

primary endpoint or a component of 

that endpoint. This draft guidance 

revises the draft guidance entitled 

‘‘Standards for Clinical Trial Imaging 

Endpoints’’ issued on August 19, 2011. 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the Agency 

considers your comment on this draft 

guidance before it begins work on the 

final version of the guidance, submit 

either electronic or written comments 

on the draft guidance by May 4, 2015. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10001 New 

Hampshire Ave., Hillandale Bldg., 4th 

Floor, Silver Spring, MD 20993–0002, or 

the Office of Communication, Outreach 

and Development, Center for Biologics 

Evaluation and Research (CBER), Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the draft guidance document. 

Submit electronic comments on the 

draft guidance to http://

www.regulations.gov. Submit written 

comments to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Louis Marzella, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 22, Rm. 5406, 

Silver Spring, MD 20993–0002, 301– 

796–1414; or Stephen Ripley, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 71, Rm. 

7301, Silver Spring, MD 20993–0002, 

240–402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Clinical Trial Imaging Endpoint 

Process Standards.’’ The purpose of this 

guidance is to assist sponsors in 

optimizing the quality of imaging data 

obtained in clinical trials intended to 

support approval of drugs and biological 

products. It focuses on imaging 

acquisition, display, archiving, and 

interpretation standards that FDA 

regards as important when imaging is 

used to assess the trial’s primary 

endpoint or a component of that 

endpoint. The guidance describes the 

minimum standards a sponsor should 

use to help ensure that clinical trial 

imaging data are obtained in a manner 

that complies with a trial’s protocol, 

maintains imaging data quality, and 

provides a verifiable record of the 

imaging process. 

This guidance addresses the 

background considerations for 

determining the role of imaging in a 

clinical trial as well as the major 

considerations in the development of an 

imaging charter that describes the trial’s 

imaging methods. The guidance 

specifically addresses the technical 

components of a charter’s description of 

the image acquisition, image 

interpretation, and image data 

development methods. 

This draft guidance revises the draft 

guidance entitled ‘‘Standards for 

Clinical Trial Imaging Endpoints’’ 

issued on August 19, 2011 (76 FR 

51993). Comments we received on the 

draft guidance have been considered 

and the guidance has been revised as 

follows: (1) It has been made clear that 

the guidance pertains to imaging in 

clinical trials intended to support 

approval of drugs and biological 

products and focuses upon standards 

that FDA regards as important when 

imaging is used to assess a trial’s 

primary endpoint; (2) it has been made 

clear that the imaging charter can be 

either a single document or an ensemble 

of documents, depending on multiple 

factors; (3) it is emphasized that imaging 

risks are best described in the clinical 

protocol and should be addressed in 

consent documents instead of including 

this information in the imaging charter; 

(4) it has been emphasized that this 

guidance does not address whether 

imaging outcomes are clinically 

meaningful and are acceptable for drug 

approval evidence; (5) it has been noted 

that image acquisition phantoms may or 

may not be necessary, depending on the 

nature of the imaging in a clinical trial; 

(6) it has been modified to emphasize 

the need for the clinical protocol (not 

the charter) to describe how incidental 

findings will be handled; (7) it has been 

noted that the charter should identify 

any use of investigational equipment 

(for international trials, the guidance 

encourages use of equipment that is 

lawfully marketed in the area); and (8) 

a section has been added that describes 

the importance of having the clinical 

trial sponsor ensure the fidelity of all 

charter components with the clinical 

protocol. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the Agency’s current thinking 

on the major considerations for 

standardization of imaging primary 

endpoints in clinical trials of drugs and 

biological products. It does not create or 

confer any rights for or on any person 

and does not operate to bind FDA or the 

public. An alternative approach may be 

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