Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices 64845 

(3) Chondroprotective effects: Pain 

intensity in OA is positively associated 

with the degree of joint degradation 

(Ref. 5). HA has been reported to have 

chondroprotective effects by reducing 

the degradation and/or restoration of 

cartilage (Refs. 11 and 14). According to 

the scientific literature, much of the 

mechanisms responsible for these 

effects are through molecular pathways 

(e.g., CD44-initiated pathways) that have 

downstream biological effects that act to 

alter the disease state of the joint by the 

synthesis of extracellular matrix (ECM) 

proteins (e.g., collagen type II) and joint 

components (e.g., increased 

proteoglycan and glycosaminoglycan) 

(Refs. 2, 9, 11, and 14). Collectively, 

these binding interactions of HA may 

act on molecular pathways that serve to 

protect and restore cartilage. 

Taken together, most of the effects 

described above (i.e., anti-inflammatory, 

analgesic, and chondroprotective) are 

achieved through various molecular 

pathways that depend on the direct 

interaction of HA with bodily 

components (e.g., cellular receptors) and 

downstream activation of specific 

signaling pathways. 

Additionally, although injection of 

HA provides mechanical effects (e.g., 

shock absorption), it is believed that 

such effects are limited due to the short 

half-life of HA (Refs. 2 and 15). 

Exogenous-introduced HA has been 

reported to have a half-life of a few days 

or up to 30 days for cross-linked 

versions (Refs. 2 and 15). Nevertheless, 

treatment with HA has been reported to 

result in clinical therapeutic effect for 

up to 6 months following injection (Ref. 

9). In other words, treatment with HA 

has been reported to continue reduction 

in pain long after it is cleared from the 

knee joint. This further supports that 

HA achieves its primary intended 

purpose of the treatment of pain in OA 

of the knee through chemical action 

within the body (e.g., through its antiinflammatory and chondroprotective 

effects that act to mitigate the 

underlying OA condition). 

Because the current published 

scientific literature supports that HA 

achieves its primary intended purpose 

of the treatment of pain in OA of the 

knee through chemical action, and 

therefore, HA for this use may not meet 

the definition of a device, sponsors of 

HA products who intend to submit a 

PMA or a supplement to a PMA for a 

change in indications for use, 

formulation, or route of administration 

are encouraged to obtain an informal or 

formal classification and jurisdictional 

determination through a Pre-RFD or 

RFD, respectively, from FDA prior to 

submission. If a sponsor believes their 

product meets the device definition, 

they may provide relevant evidence in 

the pre-RFD or RFD. 

II. References 

The following references are on 

display with the Dockets Management 

Staff (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852, and are 

available for viewing by interested 

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

Monday through Friday; these are not 

available electronically at https://

www.regulations.gov as these references 

are copyright protected. Some may be 

available at the website address, if 

listed. FDA has verified the website 

addresses, as of the date this document 

publishes in the Federal Register, but 

websites are subject to change over time. 

1. Vasi, A.M., M. Popa, M. Butnaru, et al., 

‘‘Chemical Functionalization of 

Hyaluronic Acid for Drug Delivery 

Applications.’’ Materials Science and 

Engineering, 38: 177–185, 2014. 

2. Altman, R.D., V. Dasa, and J. Takeuchi, 

‘‘Review of the Mechanism of Action for 

Supartz FX in Knee Osteoarthritis.’’ 

Cartilage, 9: 11–20, 2018. https://

www.ncbi.nlm.nih.gov/pmc/articles/ 

PMC5724672/ 

3. Greenberg, D.D., A. Stoker, S. Kane, et al., 

‘‘Biochemical Effects of Two Different 

Hyaluronic Acid Products in a CoCulture Model of Osteoarthritis.’’ 

OsteoArthritis and Cartilage, 14: 814– 

822, 2006. https://

www.sciencedirect.com/science/article/ 

pii/S1063458406000367?via%3Dihub 

4. Jahn, S., J. Seror, and J. Klein, ‘‘Lubrication 

of Articular Cartilage.’’ Annual Review of 

Biomedical Engineering, 18: 235–258, 

2016. 

5. Trouvin, A.-P. and S. Perrot, ‘‘Pain in 

Osteoarthritis. Implications for Optimal 

Management.’’ Joint Bone Spine, 85: 

429–434, 2018. 

6. Balazs, E.A., ‘‘The Physical Properties of 

Synovial Fluid and the Special Role of 

Hyaluronic Acid.’’ In Disorders of the 

Knee, A. Helfet, pp. 63–75. Philadelphia: 

Lippincott Company, 1974. 

7. Liao, Y.-H, S.A. Jones, B. Forbes, et al., 

‘‘Hyaluronan: Pharmaceutical 

Characterization and Drug Delivery.’’ 

Drug Delivery, 12: 327–342, 2005. 

https://www.tandfonline.com/doi/full/ 

10.1080/10717540590952555%20 

8. Moreland, L.W. ‘‘Intra-Articular 

Hyaluronan (hyaluronic acid) and 

Hylans for the Treatment of 

Osteoarthritis: Mechanisms of Action.’’ 

Arthritis Research and Therapy, 5: 54– 

67, 2003. https://www.ncbi.nlm.nih.gov/ 

pmc/articles/PMC165033/ 

9. Altman, R.D., A. Manjoo, A. Fierlinger, et 

al., ‘‘The Mechanism of Action for 

Hyaluronic Acid Treatment in the 

Osteoarthritic Knee: A Systematic 

Review.’’ BMC Musculoskeletal 

Disorders, 16: 321, 2015. https://

www.ncbi.nlm.nih.gov/pmc/articles/ 

PMC4621876/ 

10. Richards, M., J. Maxwell, L. Weng, et al., 

‘‘Intra-Articular Treatment of Knee 

Osteoarthritis: From Anti-inflammatories 

to Products of Regenerative Medicine.’’ 

The Physician and Sportsmedicine, 44: 

101–108, 2016. https://

www.ncbi.nlm.nih.gov/pmc/articles/ 

PMC4932822/ 

11. Nicholls, M., A. Fierlinger, F. Zaizi, et al., 

‘‘The Disease Modifying Effects of 

Hyaluronan in the Osteoarthritic Disease 

State.’’ Clinical Medicine Insights: 

Arthritis and Musculoskeletal Disorders, 

10: 1–10, 2017. https://

www.ncbi.nlm.nih.gov/pmc/articles/ 

PMC5555499/ 

12. Migliore, A. and S. Procopio, 

‘‘Effectiveness and Utility of Hyaluronic 

Acid in Osteoarthritis.’’ Clinical Cases in 

Mineral and Bone Metabolism, 12: 31– 

33, 2015. https://www.ncbi.nlm.nih.gov/ 

pmc/articles/PMC4469223/ 

13. Schaible, H.-G., F. Richter, A. Ebersberge, 

et al., ‘‘Joint Pain.’’ Experimental Brain 

Research, 196: 153–162, 2009. 

14. Chen, L., J. Xue, Z. Zheng, et al., 

‘‘Hyaluronic Acid, an Efficient 

Biomacromolecule for Treatment of 

Inflammatory Skin and Joint Diseases: A 

Review of Recent Developments and 

Critical Appraisal of Preclinical and 

Clinical Investigations.’’ International 

Journal of Biological Macromolecules, 

116: 572–584, 2018. 

15. Strauss, E., J. Hart, M. Miller, et al., 

‘‘Hyaluronic Acid Viscosupplementation 

and Osteoarthritis: Current Uses and 

Future Directions.’’ The American 

Journal of Sports Medicine, 37: 1636– 

1644, 2009. 

Dated: December 13, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–27351 Filed 12–17–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

Agency Information Collection 

Activities: Proposed Collection: Public 

Comment Request Information 

Collection Request Title: HRSA AIDS 

Education and Training Centers 

Evaluation Activities, OMB No. 0915– 

0281—Revision 

AGENCY: Health Resources and Services 

Administration (HRSA), Department of 

Health and Human Services (HHS). 

ACTION: Notice. 

SUMMARY: In compliance with the 

requirement for opportunity for public 

comment on proposed data collection 

projects of the Paperwork Reduction Act 

of 1995, HRSA announces plans to 

submit an Information Collection 

Request (ICR), described below, to the 


amozie on DSK3GDR082PROD with NOTICES
64846 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices 

Office of Management and Budget 

(OMB). Prior to submitting the ICR to 

OMB, HRSA seeks comments from the 

public regarding the burden estimate, 

below, or any other aspect of the ICR. 

DATES: Comments on this ICR should be 

received no later than February 19, 

2019. 

ADDRESSES: Submit your comments to 

paperwork@hrsa.gov or mail the HRSA 

Information Collection Clearance 

Officer, Room 14N136B, 5600 Fishers 

Lane, Rockville, MD 20857. 

FOR FURTHER INFORMATION CONTACT: To 

request more information on the 

proposed project or to obtain a copy of 

the data collection plans and draft 

instruments, email paperwork@hrsa.gov 

or call Lisa Wright-Solomon, the HRSA 

Information Collection Clearance Officer 

at (301) 443–1984. 

SUPPLEMENTARY INFORMATION: When 

submitting comments or requesting 

information, please include the 

information request collection title for 

reference, pursuant to Section 

3506(c)(2)(A), the Paperwork Reduction 

Act of 1995. 

Information Collection Request Title: 

HRSA Ryan White HIV/AIDS Program 

(RWHAP) AIDS Education and Training 

Centers (AETC) Evaluation Activities, 

OMB No. 0915–0281—Revision 

Abstract: The RWHAP AETC 

program, authorized by Title XXVI of 

the Public Health Service Act, supports 

a network of regional and national 

centers that conduct targeted, multidisciplinary education and training 

programs for health care providers 

serving people living with HIV (PLWH). 

The purpose of the RWHAP Regional 

AETC program is to increase the size 

and strengthen the skills of the current 

and novice HIV clinical workforce in 

the United States. Through the 

provision of specialized professional 

education and training, the RWHAP 

Regional AETCs aim to improve 

outcomes along the HIV care continuum 

including diagnosis, linkage, retention, 

and viral suppression and to reduce HIV 

incidence by improving the 

achievement and maintenance of viral 

load suppression of PLWH. In addition, 

the RWHAP AETC program includes the 

National Coordinating Resource Center 

(NCRC), which offers a virtual library of 

online training resources for adaptation 

by HIV care providers and other 

healthcare professionals to meet local 

training needs. The RWHAP AETC 

NCRC works closely with the HRSA 

HIV/AIDS Bureau (HAB) to coordinate 

cross-regional collaborative efforts, 

manage the NCRC website, plan and 

execute the national RWHAP Clinical 

Conference, and develop an online 

curriculum for clinical learners. 

The RWHAP AETC proposes several 

revisions to the Event Records (ER) and 

the Participant Information Form (PIF). 

The ER will have nine new data 

elements; however, only five data 

elements will require responses from all 

respondents. The option to respond to 

the other four data elements will 

depend on how participants respond to 

previous questions. The PIF will have 

one new data element that asks whether 

respondents prescribe anti-retroviral 

therapy to their patients. Three data 

elements were also deleted. These 

revisions reflect changes in the National 

AETC program guidance on reporting 

sources of funding and multi-session 

events. With a net increase of seven data 

elements across both the ER and PIF 

instruments, respondent burden is 

anticipated to increase slightly. In 

addition, HRSA HAB has modified the 

data instruments not only to improve 

the logical flow of questions within each 

instrument but also to improve the 

overall clarity of each of the questions 

being asked. 

Need and Proposed Use of the 

Information: As part of an ongoing effort 

to evaluate RWHAP AETC activities, 

information is needed on AETC training 

sessions, clinical consultations, and 

technical assistance activities. Each 

regional center collects information on 

RWHAP AETC training events and is 

required to report aggregate data on 

their activities to HRSA’s HAB. The goal 

of national data collection efforts is to 

create a uniform set of data elements 

that will produce an accurate summary 

of the national scope of RWHAP AETC 

professional training, consultation, and 

events. The elements included in the 

national database have been selected for 

their relevance in demonstrating the 

RWHAP AETCs’ efforts in achieving the 

program’s stated goals: To improve care 

for PLWH by providing education, 

training, and clinical consultation; and 

to provide support to clinicians and 

other providers. HRSA HAB uses the 

data collected when conducting 

programmatic assessments and to 

determine future program needs. The 

national data elements are intended to 

be a meaningful core set of elements 

that individual RWHAP AETCs can use 

in program and strategic planning. 

HRSA HAB also uses this information to 

respond to requests from HHS, 

Congress, and others. 

Likely Respondents: RWHAP AETC 

trainees are asked to complete the PIF 

at the start or conclusion of an event. 

Trainers are asked to complete an ER for 

each training event they conduct during 

the year. In addition, each regional 

RWHAP AETC (eight total) and the 

RWHAP AETC National Coordinating 

Resource Center will compile these data 

into a data set and submit to HRSA HAB 

once a year. 

Burden Statement: Burden in this 

context means the time expended by 

persons to generate, maintain, retain, 

disclose, or provide the information 

requested. This includes the time 

needed to review instructions; to 

develop, acquire, install, and utilize 

technology and systems for the purpose 

of collecting, validating, and verifying 

information, processing and 

maintaining information, and disclosing 

and providing information; to train 

personnel and to be able to respond to 

a collection of information; to search 

data sources; to complete and review 

the collection of information; and to 

transmit or otherwise disclose the 

information. The total annual burden 

hours estimated for this Information 

Collection Request are summarized in 

the table below. 

The estimated annual response 

burden to trainers, as well as trainees of 

training programs is follows: 

TOTAL ESTIMATED ANNUALIZED BURDEN HOURS

Form name Number of 

respondents 

Number of 

responses per 

respondent 

Total 

responses 

Average 

burden per 

response 

(in hours) 

Total burden 

hours 

Participant Information Form (PIF) ...................................... 61,288 1 61,288 0.167 10,235 

Event Record (ER) ............................................................... 10,522 1 10,522 0.200 2,104 

Total .............................................................................. 71,810 ........................ 71,810 ........................ 12,339 


amozie on DSK3GDR082PROD with NOTICES
Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices 64847 

1HRSA currently estimates approximately 10 

awardees may need to report benchmark 

performance data on a quarterly basis based on the 

statutorily-required assessment of improvement. 

2The 10 responses for Section B are a sub-set of 

56 total awardees funded through the MIECHV 

Program. 

The estimated annual burden to 

RWHAP AETCs is as follows: 

Number of 

respondents 

Responses per 

respondent 

Total 

responses 

Hours per 

response 

Total burden 

hours 

Aggregate Data Set ............................................................. 9 2 18 32 576 

HRSA specifically requests comments 

on (1) the necessity and utility of the 

proposed information collection for the 

proper performance of the agency’s 

functions, (2) the accuracy of the 

estimated burden, (3) ways to enhance 

the quality, utility, and clarity of the 

information to be collected, and (4) the 

use of automated collection techniques 

or other forms of information 

technology to minimize the information 

collection burden. 

Amy P. McNulty, 

Acting Director, Division of the Executive 

Secretariat. 

[FR Doc. 2018–27328 Filed 12–17–18; 8:45 am] 

BILLING CODE 4165–15–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

Agency Information Collection 

Activities: Submission to OMB for 

Review and Approval; Public Comment 

Request; The Maternal, Infant, and 

Early Childhood Home Visiting 

Program Quarterly Data Collection, 

OMB No. 0906–0016—Revision 

AGENCY: Health Resources and Services 

Administration (HRSA), Department of 

Health and Human Services. 

ACTION: Notice. 

SUMMARY: In compliance with the 

Paperwork Reduction Act of 1995, 

HRSA has submitted an Information 

Collection Request (ICR) to the Office of 

Management and Budget (OMB) for 

review and approval. A 60-day Federal 

Register Notice was published in the 

Federal Register on February 21, 2018. 

There were 24 public comments. 

Comments submitted during the first 

public review of this ICR will be 

provided to OMB. OMB will accept 

further comments from the public 

during the review and approval period. 

DATES: Comments on this ICR should be 

received no later than January 17, 2019. 

ADDRESSES: Submit your comments, 

including the ICR Title, to the desk 

officer for HRSA, either by email to 

OIRA_submission@omb.eop.gov or by 

fax to 202–395–5806. 

FOR FURTHER INFORMATION CONTACT: To 

request a copy of the clearance requests 

submitted to OMB for review, email Lisa 

Wright-Solomon, the HRSA Information 

Collection Clearance Officer at 

paperwork@hrsa.gov or call (301) 443– 

1984. 

SUPPLEMENTARY INFORMATION: 

Information Collection Request Title: 

The Maternal, Infant, and Early 

Childhood Home Visiting Program 

Quarterly Data Collection, OMB 

Number: 0906–0016—Revision. 

Abstract: This clearance request is for 

continued approval of the Maternal, 

Infant, and Early Childhood Home 

Visiting (MIECHV) Program Quarterly 

Data Collection. The MIECHV Program, 

administered by HRSA in partnership 

with the Administration for Children 

and Families (ACF), supports voluntary, 

evidence-based home visiting services 

during pregnancy and to parents with 

young children up to kindergarten 

entry. States, certain non-profit 

organizations, and Tribal entities are 

eligible to receive funding from the 

MIECHV Program and have the 

flexibility to tailor the program to serve 

the specific needs of their communities. 

After taking into consideration public 

comments in response to the 60-day 

notice published in the Federal Register 

on February 21, 2018 (83 FR 7481), 

HRSA is proposing revisions to the data 

collection forms for the MIECHV 

Program by making the following 

changes: 

• Form 4, Due date: The due date will 

be revised from 60 days to 30 days after 

the end of each reporting period. 

• Form 4, Section A: All tables will be 

renumbered. 

• Form 4, Table A.2: Columns will be 

revised to reflect Local Implementing 

Agencies (LIAs) served, LIA addresses, 

counties served, zip codes served, and 

evidence-based home visiting models 

implemented. 

• Form 4, Table A.4.1: Columns will 

be combined to reflect number of fulltime equivalents (FTEs) for home 

visitors, supervisors, and other staff. 

• Form 4, Table A.4.2: Table will be 

deleted. 

• Form 4, Section B: Section will be 

updated to reflect current benchmark 

constructs. 

• Form 4, Definitions of Key Terms: 

Update definitions for all tables. HRSA 

is requesting approval of this revised 

information collection request through 

March 31, 2022. 

Need and Proposed Use of the 

Information: HRSA uses quarterly 

performance information to demonstrate 

program accountability and 

continuously monitor and provide 

oversight to MIECHV Program awardees. 

The information is also used to provide 

quality improvement guidance and 

technical assistance to awardees and 

help inform the development of early 

childhood systems at the national, state, 

and local level. HRSA is seeking to 

revise place-based services and staffing 

indicators for home visiting programs. 

In addition, on a quarterly basis HRSA 

will collect a set of standardized 

performance and outcome indicators 

that correspond with the benchmark 

areas identified in statute for awardees 

who fail to demonstrate improvement 

through the required 3-year assessment 

of improvement. 

Likely Respondents: MIECHV Program 

awardees (n=56). 

Burden Statement: Burden in this 

context means the time expended by 

persons to generate, maintain, retain, 

disclose, or provide the information 

requested. This includes the time 

needed to review instructions; to 

develop, acquire, install, and utilize 

technology and systems for the purpose 

of collecting, validating, and verifying 

information, processing and 

maintaining information, and disclosing 

and providing information; to train 

personnel and to be able to respond to 

a collection of information; to search 

data sources; to complete and review 

the collection of information; and to 

transmit or otherwise disclose the 

information. The total annual burden 

hours estimated for this ICR are 

summarized in the table below: 


amozie on DSK3GDR082PROD with NOTICES