Agency Emergency Processing Request Under OMB Review

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D-0143]

Agency Emergency Processing Request Under OMB Review

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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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 emergency processing under the

Paperwork Reduction Act of 1995 (the PRA). The proposed collection of

information concerns procedures recommended in a guidance entitled

``Guidance for Industry: Current Good Manufacturing Practice for Blood

and Blood Components: (1) Quarantine and Disposition of Units From

Prior Collections From Donors With Repeatedly Reactive Screening Test

for Antibody to Hepatitis C Virus (Anti-HCV); (2) Supplemental Testing,

and the Notification of Consignees and Blood Recipients of Donor Test

Results for Anti-HCV.''

DATES: Submit written comments on the collection of information by

November 2, 1998.

ADDRESSES: Submit written comments on the collection of information to

the Office of Information and Regulatory Affairs, OMB, New Executive

Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn:

Desk Officer for FDA. All comments should be identified with the docket

number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: JonnaLynn P. Capezzuto, Office of

Information Resources Management (HFA-250), Food and Drug

Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: With respect to the following collection of

information, FDA invites comments on: (1) Whether the proposed

collection of information is necessary for the proper performance of

FDA's functions, including whether the information will have practical

utility; (2) the accuracy of FDA's estimate of the burden of the

proposed collection of information, including the validity of the

methodology and assumptions used; (3) ways to enhance the quality,

utility, and clarity of the information to be collected; and (4) ways

to minimize the burden of the collection of information on respondents,

including through the use of automated collection techniques, when

appropriate, and other forms of information technology.

Guidance for Industry: Current Good Manufacturing Practice for

Blood and Blood Components: (1) Quarantine and Disposition of Units

From Prior Collections From Donors With Repeatedly Reactive

Screening Test for Antibody to Hepatitis C Virus (Anti-HCV); (2)

Supplemental Testing, and the Notification of Consignees and Blood

Recipients of Donor Test Results for Anti-HCV

Elsewhere in this issue of the Federal Register, FDA is announcing

the availability of a guidance entitled ``Guidance for Industry:

Current Good Manufacturing Practice for Blood and Blood Components: (1)

Quarantine and

[[Page 56193]]

Disposition of Units From Prior Collections From Donors With Repeatedly

Reactive Screening Test for Antibody to Hepatitis C Virus (Anti-HCV);

(2) Supplemental Testing, and the Notification of Consignees and Blood

Recipients of Donor Test Results for Anti-HCV.'' The guidance document

provides recommendations for donor screening and supplemental testing

for antibody to HCV, quarantine of prior collections from a donor who

later tests repeatedly reactive for antibody to HCV, and notification

and counseling of recipients of blood and blood components at increased

risk for transmitting HCV. The statutory authority to collect this

information is provided under sections 351 and 361 of the Public Health

Service Act (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.

201 et seq.). The purpose of this guidance is to help ensure the

continued safety of the blood supply by preventing the introduction,

transmission, and spread of HCV. The collection of information

described in the guidance will help ensure that important information

is provided to consignees and recipients of blood and blood components

from a donor who later tests positive for HCV. Also, the collection of

information will enable consignees to identify and quarantine product

that may be at increased risk for transmitting HCV. As a result,

transfusion recipients of such product may have the opportunity to seek

medical counseling.

Lookback (product retrieval and recipient notification) related to

hepatitis B virus (HBV), HCV, and human T-lymphotropic virus (HTLV-I)

testing has been discussed at open public meetings, including meetings

of FDA's Blood Products Advisory Committee, on multiple occasions since

October 1989. As a response to these discussions, FDA provided detailed

guidance in the July 19, 1996, memorandum on the quarantine and

disposition of certain prior collections of blood and blood components

from donors who subsequently test repeatedly reactive for hepatitis B

surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-

HBc), anti-HCV, or antibody to HTLV type I (anti-HTLV-I). The

memorandum recommended that blood establishments notify consignees

(such as the transfusion service, physician, fractionator, etc.) for

the purpose of quarantine and eventual disposition of products made

from prior collections. At that time, FDA did not recommend

notification of recipients of blood from donors who subsequently test

positive for anti-HCV, because no clear consensus on the public health

benefit of such action had emerged.

Improvements in the treatment and management of HCV infections have

occurred recently, and at public meetings on April 24 and 25, 1997, and

August 11 and 12, 1997, the PHS Advisory Committee on Blood Safety and

Availability discussed recipient notification related to hepatitis C.

Consistent with recommendations of the Public Health Service Advisory

Committee, in the Federal Register of March 20, 1998 (63 FR 13675), FDA

issued a guidance regarding such notification for implementation and

comment. In response to comments received, FDA is now issuing the

previously referenced guidance, which supersedes the guidance issued on

July 19, 1996, and replaces the guidance issued on March 20, 1998.

Description: This guidance recommends that blood establishments

prepare and follow written procedures when blood establishments have

collected Whole Blood, blood components, Source Plasma, and Source

Leukocytes later determined to be at risk for transmitting HCV

infections. This guidance provides recommendations, similar to the

requirements now in effect for HIV ``Lookback'' (21 CFR 610.46 and

610.47), to clarify the status of the donor who later tests repeatedly

reactive for HCV, to quarantine prior collections from such donors, and

to notify transfusion recipients, as appropriate, based on further

testing of the donor. The guidance recommends that when a donor who

previously donated blood is tested in accordance with this guidance on

a later donation, and tests repeatedly reactive for antibody to HCV,

the blood establishment should perform a supplemental test using a

licensed test, and notify consignees who received Whole Blood, blood

components, Source Plasma, and Source Leukocytes from prior collections

so that appropriate action is taken. The guidance document recommends

that blood establishments and consignees quarantine previously

collected Whole Blood, blood components, Source Plasma and Source

Leukocytes from such donors, and if appropriate, consignees should

notify transfusion recipients. In addition to the prospective

``lookback'' recommendations that are similar to the ``lookback''

requirements for HIV, this guidance recommends a retrospective review

of testing records that should identify prior collections from donors

at increased risk for transmitting HCV as far back as 10 years. Under

this guidance, it is suggested that blood establishments notify

consignees of the risk of HCV transmission that exists for prior

collections based on the retrospective review of record and the results

of the supplemental testing performed before or as a result of the

retrospective review of records. In addition, the guidance recommends

that blood establishments notify consignees of the risk of HCV

transmission that exists for prior collections from a donor who tested

repeatedly reactive on a screening test for HCV and has no record of

further testing and now cannot be clarified because further testing is

impractical or infeasible. This guidance recommends that blood

establishments maintain records of the source and disposition of all

units of blood and blood products for at least 10 years from the date

of disposition or 6 months after the latest product expiration date,

whichever is the later date. Under 21 CFR 606.160, such records are

required to be retained for 5 years. FDA is recommending an extended

records retention period because advances in medical diagnosis and

therapy have created opportunities for disease prevention or treatment

many years after recipient exposure to a donor later determined to be

at increased risk for transfusion-transmitted disease. Additionally,

methods of recordkeeping have advanced, improving the ability of blood

establishments to more easily maintain and retrieve records. Also, this

guidance recommends that any consignee of a blood establishment notify

the transfusion recipients of blood and blood components at increased

risk for transmitting HCV.

The agency is issuing this guidance to promote the continued safety

of the blood supply, to help provide users with critical information

about blood and blood components, and to promote notification to

transfusion recipients regarding receipt of blood and blood components

at risk for transmitting HCV.

Description of Respondents: Blood establishments (Business and Not-

for-Profit) and consignees of blood establishments, including

hospitals, transfusion services, and physicians.

The total reporting and recordkeeping burden is estimated to be

285,867 hours. However, of this total approximately 268,374 hours would

be expended on a one-time basis for establishing the written procedures

and doing the one-time retrospective review of records. Therefore,

17,493 hours is estimated as the ongoing annual burden related to this

guidance. The total ongoing

[[Page 56194]]

prospective annual burden for blood establishments is estimated to be

12,630 hours. The prospective annual burden for consignees of blood

establishments is estimated to be 4,863 hours.

The burden estimates are based on Health Care Financing

Administration (HCFA) and FDA registration records and the following

estimates from the Centers for Disease Control and Prevention (CDC).

CDC estimates there are approximately 9,750,127 donations from repeat

donors per year and the prevalence of HCV among donors is 0.27 percent.

Therefore, CDC estimates that 26,325 repeat donors per year could test

repeatedly reactive for HCV. For each of these donors, the

recommendations in this guidance call for blood establishments to

notify the consignee (transfusion service) two times (once for

quarantine purposes and again with supplemental test results) for a

total 52,650 notifications as an annual ongoing burden. Based on

estimates from CDC, FDA expects that for the one-time review of

records, as many as 237,688 blood products would be at increased risk

for transmitting HCV. Therefore, FDA estimates that for each of these

products, blood establishments should notify consignees to quarantine

these products, should report supplemental test results to consignees,

and consignees should notify recipients or the recipients' attending

physician. The guidance recommends that blood establishments notify the

consignees two times (once for quarantine purposes and again with

supplemental test results) for a total of 475,376 notifications as a

result of the retrospective review. The total annual responses for

blood establishments is estimated to be the combined number of

notifications (475,376 + 52,650) or 528,026. FDA estimates the amount

of time for each notification of a consignee by a blood establishment

will be approximately 12 minutes (0.2 hours). Consequently, the total

estimated reporting burden hours for blood establishments is (528,026

report notifications x 0.2 hrs) 105,605 hours. However, the ongoing

annual burden not associated with the retrospective review would be

10,530 hours (52,650 x 0.2 hours).

CDC expects that approximately 2,730 repeat donors who have

repeatedly reactive HCV screening test results will confirm positive

for HCV each year. Based on CDC's research and information, a donor who

confirms positive for HCV will have donated on the average only two

previous times and on the average only 1.6 components will have been

made from each donation. Based on this information, there could be

8,736 transfusion recipients that should be notified per year (2,730

repeat donors per year that confirm positive for HCV x 2 prior

donations per donor x 1.6 components per donation). Thus, the total

notifications by consignees is estimated to be 246,424 annually (8,736

transfusion recipients who may be at increased risk of transmitting HCV

plus the estimated 237,688 transfusion recipients identified from a

retrospective review). The time estimated for consignees to make a

notification is 30 minutes or 0.5 hours on average. This time, which is

somewhat longer than for blood establishments to notify consignees,

allows for the possibility of having to make up to three attempts to

complete the notification process and creates a total reporting burden

of 123,212 hours. However, the ongoing annual reporting burden for

consignees is expected to be only 4,368 hours (8,736 recipients per

year x 0.5 hours). According to the HCFA, there are approximately 6,200

consignees that should be responsible for notification.

In the recordkeeping Table 2 of this document, the 8.75 hours per

blood establishment recordkeeper represents 8 hours to develop written

procedures for the HCV lookback recommendations and 0.75 hours to

update 9 HCV repeat reactive records (frequency of recordkeeping is 10

less 1 written procedure = 9 HCV testing records on average). FDA

estimates that it takes approximately 5 minutes to update each record

(9 x 5 minutes = 45 minutes or 0.75 hours per recordkeeper). Therefore,

the total recordkeeping by blood establishments is estimated to be

24,500 hours. Likewise, the 5.25 hours per consignee recordkeeper

includes 2 hours to develop written procedures for the HCV lookback

notification process and 3.25 hours to update 39 transfusion recipient

records (frequency of consignee recordkeeping is 40 less 1 written

procedure = 39 recipient records on average). FDA estimates that it

takes approximately 5 minutes to update each record (39 x 5 minutes =

195 minutes or 3.25 hours). Therefore, the total recordkeeping burden

for consignees is estimated to be 32,550. The combined total

recordkeeping burden for both blood establishments and consignees is

estimated to be 57,050 hours. However, based on the prospective number

of repeat donors per year and the number that confirm positive for HCV,

the ongoing annual recordkeeping burden may only be 2,596 hours. Over

time we expect the ongoing annual recordkeeping burden to decline much

as the prevalence of HCV among donors has declined due to the

implementation of screening tests for anti-HCV which helps to reduce

the number of donors infected with HCV from the donor pool.

FDA estimates the burden for this collection of information as

follows:

Table 1.--Estimated Annual Reporting Burden1

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Annual

Collection Activity No. of Frequency per Total Annual Hours per Total Hours

Respondents Response Responses Response

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Blood Establishments 2,800 38 528,026 .2 105,605

Consignees 6,200 40 246,424 .5 123,212

Total 228,817

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

Table 2.--Estimated Annual Recordkeeping Burden1

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Annual

Collection Activity No. of Frequency per Total Annual Hours per Total Hours

Recordkeepers Recordkeeping Records Recordkeeper

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Blood Establishments 2,800 10 29,125 8.75 24,500

Consignees 6,200 40 252,624 5.25 32,550

[[Page 56195]]

Total 57,050

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

Maintenance costs were not estimated for the additional maintenance

of records beyond the current 5 years to the recommended 10 years,

because modern storage technology has markedly reduced the space needed

to store records.

FDA has requested emergency processing of this proposed collection

of information under section 3507(j) of the PRA and 5 CFR 1320.13.

Because HCV frequently causes chronic infection of the liver, it can

cause serious liver injury and can be life threatening, and because new

therapies are recently available, it is essential to the agency's

mission of protecting and promoting the public health that this

guidance be made available to the public immediately. The information

is needed immediately to replace the March 20, 1998, guidance that was

withdrawn September 8, 1998. The use of normal clearance procedures

could take 180 days or more, during which time guidance would not be in

place, thus disrupting or preventing this collection of information.

Dated: October 14, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-28218 Filed 10-20-98; 8:45 am]

BILLING CODE 4160-01-F