4628 Federal Register / Vol. 81, No. 17 / Wednesday, January 27, 2016 / Notices 

may request; and (2) provide advice to 

the President concerning the following 

for people with intellectual disabilities: 

(A) Expansion of educational 

opportunities; (B) promotion of 

homeownership; (C) assurance of 

workplace integration; (D) improvement 

of transportation options; (E) expansion 

of full access to community living; and 

(F) increasing access to assistive and 

universally designed technologies. 

Agenda: The Committee Members 

will discuss preparation of the PCPID 

2016 Report to the President, including 

its contents and format, and related data 

collection and analysis required to 

complete the writing of the Report in 

the following focus areas: 

Family engagement early on in the 

process to support high expectations for 

students with disabilities. 

Federal policies and enforcement 

strategies to end segregation in schools 

and other aspects of community living 

beyond graduation. 

Transition as a critical area for 

pathways to higher education and career 

development. 

Self-determination/Supported 

decision-making from early childhood 

throughout the individual’s lifespan. 

Dated: January 14, 2016. 

Aaron Bishop, 

Commissioner, Administration on 

Disabilities. 

[FR Doc. 2016–01586 Filed 1–26–16; 8:45 am] 

BILLING CODE 4154–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2012–N–0559] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Public Health 

Service Guideline on Infectious 

Disease Issues in Xenotransplantation 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a proposed collection of 

information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Fax written comments on the 

collection of information by February 

26, 2016. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: FDA Desk Officer, FAX: 

202–395–7285, or emailed to oira_

submission@omb.eop.gov. All 

comments should be identified with the 

OMB control number 0910–0456. Also 

include the FDA docket number found 

in brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: FDA 

PRA Staff, Office of Operations, Food 

and Drug Administration, 8455 

Colesville Rd., COLE–14526, Silver 

Spring, MD 20993–0002, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

PHS Guideline on Infectious Disease 

Issues in Xenotransplantation 

OMB Control Number 0910–0456— 

Extension 

The statutory authority to collect this 

information is provided under sections 

351 and 361 of the PHS Act (42 U.S.C. 

262 and 264) and the provisions of the 

Federal Food, Drug, and Cosmetic Act 

that apply to drugs (21 U.S.C. 301 et 

seq.). The PHS guideline recommends 

procedures to diminish the risk of 

transmission of infectious agents to the 

xenotransplantation product recipient 

and to the general public. The PHS 

guideline is intended to address public 

health issues raised by 

xenotransplantation, through 

identification of general principles of 

prevention and control of infectious 

diseases associated with 

xenotransplantation that may pose a 

hazard to the public health. The 

collection of information described in 

this guideline is intended to provide 

general guidance on the following 

topics: (1) The development of 

xenotransplantation clinical protocols; 

(2) the preparation of submissions to 

FDA; and (3) the conduct of 

xenotransplantation clinical trials. Also, 

the collection of information will help 

ensure that the sponsor maintains 

important information in a crossreferenced system that links the relevant 

records of the xenotransplantation 

product recipient, xenotransplantation 

product, source animal(s), animal 

procurement center, and significant 

nosocomial exposures. The PHS 

guideline describes an occupational 

health service program for the 

protection of health care workers 

involved in xenotransplantation 

procedures, caring for 

xenotransplantation product recipients, 

and performing associated laboratory 

testing. The PHS guideline is intended 

to protect the public health and to help 

ensure the safety of using 

xenotransplantation products in 

humans by preventing the introduction, 

transmission, and spread of infectious 

diseases associated with 

xenotransplantation. 

The PHS guideline also recommends 

that certain specimens and records be 

maintained for 50 years beyond the date 

of the xenotransplantation. These 

include: (1) Records linking each 

xenotransplantation product recipient 

with relevant health records of the 

source animal, herd or colony, and the 

specific organ, tissue, or cell type 

included in or used in the manufacture 

of the product (section 3.2.7.1); (2) 

aliquots of serum samples from 

randomly selected animal and specific 

disease investigations (section 3.4.3.1); 

(3) source animal biological specimens 

designated for PHS use (section 3.7.1); 

animal health records (section 3.7.2), 

including necropsy results (section 

3.6.4); and (4) recipients’ biological 

specimens (section 4.1.2). The retention 

period is intended to assist health care 

practitioners and officials in 

surveillance and in tracking the source 

of an infection, disease, or illness that 

might emerge in the recipient, the 

source animal, or the animal herd or 

colony after a xenotransplantation. 

The recommendation for maintaining 

records for 50 years is based on clinical 

experience with several human viruses 

that have presented problems in human 

to human transplantation and are 

therefore thought to share certain 

characteristics with viruses that may 

pose potential risks in 

xenotransplantation. These 

characteristics include long latency 

periods and the ability to establish 

persistent infections. Several also share 

the possibility of transmission among 

individuals through intimate contact 

with human body fluids. Human 

immunodeficiency virus (HIV) and 

human T-lymphotropic virus are human 

retroviruses. Retroviruses contain 

ribonucleic acid that is reversetranscribed into deoxyribonucleic acid 

(DNA) using an enzyme provided by the 

virus and the human cell machinery. 

That viral DNA can then be integrated 

into the human cellular DNA. Both 

viruses establish persistent infections 

and have long latency periods before the 

onset of disease; 10 years and 40 to 60 

years, respectively. The human hepatitis 

viruses are not retroviruses, but several 

share with HIV the characteristic that 

they can be transmitted through body 


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Federal Register / Vol. 81, No. 17 / Wednesday, January 27, 2016 / Notices 4629 

fluids, can establish persistent 

infections, and have long latency 

periods, e.g., approximately 30 years for 

hepatitis C. 

In addition, the PHS guideline 

recommends that a record system be 

developed that allows easy, accurate, 

and rapid linkage of information among 

the specimen archive, the recipient’s 

medical records, and the records of the 

source animal for 50 years. The 

development of such a record system is 

a one-time burden. Such a system is 

intended to cross-reference and locate 

relevant records of recipients, products, 

source animals, animal procurement 

centers, and nosocomial exposures. 

Respondents to this collection of 

information are the sponsors of clinical 

studies of investigational 

xenotransplantation products under 

investigational new drug applications 

(INDs) and xenotransplantation product 

procurement centers, referred to as 

source animal facilities. There are an 

estimated three respondents who are 

sponsors of INDs that include protocols 

for xenotransplantation in humans and 

five clinical centers doing 

xenotransplantation procedures. Other 

respondents for this collection of 

information are an estimated four source 

animal facilities which provide source 

xenotransplantation product material to 

sponsors for use in human 

xenotransplantation procedures. These 

four source animal facilities keep 

medical records of the herds/colonies as 

well as the medical records of the 

individual source animal(s). The burden 

estimates are based on FDA’s records of 

xenotransplantation-related INDs and 

estimates of time required to complete 

the various reporting, recordkeeping, 

and third-party disclosure tasks 

described in the PHS guideline. 

FDA is requesting an extension of 

OMB approval for the following 

reporting, recordkeeping, and thirdparty disclosure recommendations in 

the PHS guideline: 

TABLE 1—REPORTING RECOMMENDATIONS

PHS guideline section Description 

3.2.7.2 ................................... Notify sponsor or FDA of new archive site when the source animal facility or sponsor ceases operations. 

TABLE 2—RECORDKEEPING RECOMMENDATIONS

PHS guideline section Description 

3.2.7 ...................................... Establish records linking each xenotransplantation product recipient with relevant records. 

4.3 ......................................... Sponsor to maintain cross-referenced system that links all relevant records (recipient, product, source animal, 

animal procurement center, and nosocomial exposures). 

3.4.2 ...................................... Document results of monitoring program used to detect introduction of infectious agents which may not be apparent clinically. 

3.4.3.2 ................................... Document full necropsy investigations including evaluation for infectious etiologies.

3.5.1 ...................................... Justify shortening a source animal’s quarantine period of 3 weeks prior to xenotransplantation product procurement. 

3.5.2 ...................................... Document absence of infectious agent in xenotransplantation product if its presence elsewhere in source animal 

does not preclude using it. 

3.5.4 ...................................... Add summary of individual source animal record to permanent medical record of the xenotransplantation product 

recipient. 

3.6.4 ...................................... Document complete necropsy results on source animals (50-year record retention). 

3.7 ......................................... Link xenotransplantation product recipients to individual source animal records and archived biologic specimens. 

4.2.3.2 ................................... Record baseline sera of xenotransplantation health care workers and specific nosocomial exposure. 

4.2.3.3 and 4.3.2 ................... Keep a log of health care workers’ significant nosocomial exposure(s). 

4.3.1 ...................................... Document each xenotransplant procedure. 

5.2 ......................................... Document location and nature of archived PHS specimens in health care records of xenotransplantation product 

recipient and source animal. 

TABLE 3—DISCLOSURE RECOMMENDATIONS

PHS guideline section Description 

3.2.7.2 ................................... Notify sponsor or FDA of new archive site when the source animal facility or sponsor ceases operations. 

3.4 ......................................... Standard operating procedures (SOPs) of source animal facility should be available to review bodies. 

3.5.1 ...................................... Include increased infectious risk in informed consent if source animal quarantine period of 3 weeks is shortened. 

3.5.4 ...................................... Sponsor to make linked records described in section 3.2.7 available for review. 

3.5.5 ...................................... Source animal facility to notify clinical center when infectious agent is identified in source animal or herd after 

xenotransplantation product procurement. 

In the Federal Register of October 5, 

2015 (80 FR 60153), FDA published a 

60-day notice requesting public 

comment on the proposed collection of 

information. FDA received one 

comment from the public. The comment 

was supportive of the extended 

recordkeeping requirements in case it 

would be necessary to track the source 

of any long-term developing infections 

as result of xenotransplantation. 

FDA estimates the burden for this 

collection of information as follows: 


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TABLE 4—ESTIMATED ANNUAL REPORTING BURDEN 1

PHS guideline section Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

3.2.7.2 2 ........................................................... 1 1 1 0.5 (30 minutes) ................. 0.5 

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

2FDA is using 1 animal facility or sponsor for estimation purposes. 

TABLE 5—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

PHS guideline section Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeping 

Total hours 

3.2.7 2 .............................................................. 1 1 1 16 ....................................... 16 

4.3 3 ................................................................. 3 1 3 0.75 (45 minutes) ............... 2.25 

3.4.2 4 .............................................................. 3 10.67 32 0.25 (15 minutes) ............... 8 

3.4.3.2 5 ........................................................... 3 2.67 8 0.25 (15 minutes) ............... 2 

3.5.1 6 .............................................................. 3 0.33 1 0.50 (30 minutes) ............... 0.5 

3.5.2 6 .............................................................. 3 0.33 1 0.25 (15 minutes) ............... 0.25 

3.5.4 ................................................................ 3 1 3 0.17 (10 minutes) ............... 0.51 

3.6.4 7 .............................................................. 3 2.67 8 0.25 (15 minutes) ............... 2 

3.7 7 ................................................................. 4 2 8 0.08 (5 minutes) ................. 0.64 

4.2.3.2 8 ........................................................... 5 25 125 0.17 (10 minutes) ............... 21.25 

4.2.3.2 6 ........................................................... 5 0.20 1 0.17 (10 minutes) ............... 0.17 

4.2.3.3 and 4.3.2 6 ........................................... 5 0.20 1 0.17 (10 minutes) ............... 0.17 

4.3.1 ................................................................ 3 1 3 0.25 (15 minutes) ............... 0.75 

5.2 9 ................................................................. 3 4 12 0.08 (5 minutes) ................. 0.96 

Total ......................................................... ........................ ........................ ........................ ............................................. 55.45 

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

2A one-time burden for new respondents to set up a recordkeeping system linking all relevant records. FDA is using one new sponsor for estimation purposes. 3FDA estimates there is minimal recordkeeping burden associated with maintaining the record system. 

4 Monitoring for sentinel animals (subset representative of herd) plus all source animals. There are approximately 6 sentinel animals per herd × 

1 herd per facility × 4 facilities = 24 sentinel animals. There are approximately 8 source animals per year (see footnote 7 of this table); 24 + 8 = 

32 monitoring records to document. 5 Necropsy for animal deaths of unknown cause estimated to be approximately 2 per herd per year × 1 herd per facility × 4 facilities = 8. 6 Has not occurred in the past 3 years and is expected to continue to be a rare occurrence. 

7On average 2 source animals are used for preparing xenotransplantation product material for one recipient. The average number of source 

animals is 2 source animals per recipient × 4 recipients annually = 8 source animals per year. (See footnote 5 of table 6.) 8FDA estimates there are 5 clinical centers doing xenotransplantation procedures × approximately 25 health care workers involved per center 

= 125 health care workers. 9Eight source animal records + 4 recipient records = 12 total records. 

TABLE 6—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN

PHS guideline section Number of 

respondents 

Number of 

disclosures 

per 

respondent 

Total annual 

disclosures 

Average 

burden per 

disclosure 

Total hours 

3.2.7.2 2 ........................................................... 1 1 1 0.5 (30 minutes) ................. 0.5 

3.4 3 ................................................................. 4 0.25 1 0.08 (5 minutes) ................. 0.08 

3.5.1 4 .............................................................. 4 0.25 1 0.25 (15 minutes) ............... 0.25 

3.5.4 5 .............................................................. 4 1 4 0.5 (30 minutes) ................. 2 

3.5.5 4 .............................................................. 4 0.25 1 0.25 (15 minutes) ............... 0.25 

Total ......................................................... ........................ ........................ ........................ ............................................. 3.08 

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

2FDA is using one animal facility or sponsor for estimation purposes. 

3FDA’s records indicate that an average of 1 IND is expected to be submitted per year. 

4To our knowledge, has not occurred in the past 3 years and is expected to continue to be a rare occurrence. 

5Based on an estimate of 12 patients treated over a 3-year period, the average number of xenotransplantation product recipients per year is 

estimated to be 4. 

Because of the potential risk for crossspecies transmission of pathogenic 

persistent virus, the guideline 

recommends that health records be 

retained for 50 years. Since these 

records are medical records, the 

retention of such records for up to 50 

years is not information subject to the 

PRA (5 CFR 1320.3(h)(5)). Also, because 

of the limited number of clinical studies 

with small patient populations, the 

number of records is expected to be 

insignificant at this time. 

Information collections in this 

guideline not included in tables 1 

through 6 can be found under existing 

regulations and approved under the 


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OMB control numbers as follows: (1) 

‘‘Current Good Manufacturing Practice 

for Finished Pharmaceuticals,’’ 21 CFR 

211.1 through 211.208, approved under 

OMB control number 0910–0139; (2) 

‘‘Investigational New Drug 

Application,’’ 21 CFR 312.1 through 

312.160, approved under OMB control 

number 0910–0014; and (3) information 

included in a biologics license 

application, 21 CFR 601.2, approved 

under OMB control number 0910–0338. 

(Although it is possible that a 

xenotransplantation product may not be 

regulated as a biological product (e.g., it 

may be regulated as a medical device), 

FDA believes, based on its knowledge 

and experience with 

xenotransplantation, that any 

xenotransplantation product subject to 

FDA regulation within the next 3 years 

will most likely be regulated as a 

biological product.) However, FDA 

recognized that some of the information 

collections go beyond approved 

collections; assessments for these 

burdens are included in tables 1 through 

6. 

In table 7, FDA identifies those 

collections of information activities that 

are already encompassed by existing 

regulations or are consistent with 

voluntary standards which reflect 

industry’s usual and customary business 

practice. 

TABLE 7—COLLECTION OF INFORMATION REQUIRED BY CURRENT REGULATIONS AND STANDARDS

PHS guideline section Description of collection of information activity 21 CFR section 

(unless otherwise stated) 

2.2.1 ....................................... Document offsite collaborations ................................................................... 312.52. 

2.5 .......................................... Sponsor ensures counseling patient + family + contacts ............................ 312.62(c). 

3.1.1 and 3.1.6 ....................... Document well-characterized health history and lineage of source animals.312.23(a)(7)(a) and 211.84. 

3.1.8 ....................................... Registration with and import permit from the Centers for Disease Control 

and Prevention.

42 CFR 71.53. 

3.2.2 ....................................... Document collaboration with accredited microbiology labs ......................... 312.52. 

3.2.3 ....................................... Procedures to ensure the humane care of animals .................................... 9 CFR parts 1, 2, and 3 and PHS 

Policy.1

3.2.4 ....................................... Procedures consistent for accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International 

(AAALAC International) and consistent with the National Research 

Council’s (NRC) Guide.

AAALAC International Rules of Accreditation 2 and NRC Guide.3

3.2.5, 3.4, and 3.4.1 .............. Herd health maintenance and surveillance to be documented, available, 

and in accordance with documented procedures; record standard veterinary care.

211.100 and 211.122. 

3.2.6 ....................................... Animal facility SOPs .................................................................................... PHS Policy.1

3.3.3 ....................................... Validate assay methods ............................................................................... 211.160(a). 

3.6.1 ....................................... Procurement and processing of xenografts using documented aseptic 

conditions.

211.100 and 211.122. 

3.6.2 ....................................... Develop, implement, and enforce SOPs for procurement and screening 

processes.

211.84(d) and 211.122(c). 

3.6.4 ....................................... Communicate to FDA animal necropsy findings pertinent to health of recipient.312.32(c). 

3.7.1 ....................................... PHS specimens to be linked to health records; provide to FDA justification for types of tissues, cells, and plasma, and quantities of plasma 

and leukocytes collected.

312.23(a)(6). 

4.1.1 ....................................... Surveillance of xenotransplant recipient; sponsor ensures documentation 

of surveillance program life-long (justify >2 yrs.); investigator case histories (2 yrs. after investigation is discontinued).

312.23(a)(6)(iii)(f) and (g), and 

312.62(b) and (c). 

4.1.2 ....................................... Sponsor to justify amount and type of reserve samples ............................. 211.122. 

4.1.2.2 .................................... System for prompt retrieval of PHS specimens and linkage to medical 

records (recipient and source animal).

312.57(a). 

4.1.2.3 .................................... Notify FDA of a clinical episode potentially representing a xenogeneic infection.312.32. 

4.2.2.1 .................................... Document collaborations (transfer of obligation) ......................................... 312.52. 

4.2.3.1 .................................... Develop educational materials (sponsor provides investigators with information needed to conduct investigation properly).312.50. 

4.3 .......................................... Sponsor to keep records of receipt, shipment, and disposition of investigative drug; investigator to keep records of case histories.312.57 and 312.62(b). 

1The ‘‘Public Health Service Policy on Humane Care and Use of Laboratory Animals’’ (http://www.grants.nih.gov/grants/olaw/references/

phspol.htm). 2AAALAC International Rules of Accreditation (http://www.aaalac.org/accreditation/rules.cfm). 3The NRC’s ‘‘Guide for the Care and Use of Laboratory Animals.’’ 

Dated: January 22, 2016. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2016–01638 Filed 1–26–16; 8:45 am] 

BILLING CODE 4164–01–P 


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