OMB INFORMATION COLLECTION

SUPPORTING STATEMENT

0910-0116

Current Good Manufacturing Practices and Related Regulations for Blood
and Blood Components; and "Lookback" Requirements

# [JUSTIFICATION]{.underline}

1.  **[Circumstances Which Make This Information Collection
    Necessary]{.underline}**

The Food and Drug Administration (FDA) is requesting an extension of OMB
Control No. 0910-0116 and OMB approval of the information collection
requirements in 21 CFR Parts 606, 640, 610.46 and 610.47 (Tab A),
Current Good Manufacturing Practices and Related Regulations for Blood
and Blood Components; and "Lookback" Requirements:

+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires that written standard operating   |
|           | ordkeeping | procedures (SOPs) be maintained for the    |
| 6         |            | collection, processing, compatibility      |
| 06.100(b) |            | testing, storage and distribution of blood |
|           |            | and blood components used for transfusion  |
|           |            | and manufacturing purposes.                |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires the review of all pertinent       |
|           | ordkeeping | records to a lot or unit of blood prior to |
| 6         |            | release of the lot or unit. Conclusions    |
| 06.100(c) |            | and followup of any unexplained            |
|           |            | discrepancy or failure of a lot or unit of |
|           |            | final product to meet any of its           |
|           |            | specifications shall be recorded.          |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires a physician to certify in writing |
|           | ordkeeping | that the donor's health permits            |
| 6         |            | plateletpheresis or leukapheresis if a     |
| 06.110(a) |            | variance from additional regulatory        |
|           |            | standards for a specific product is used   |
|           |            | when obtaining the product from a specific |
|           |            | donor for a specific recipient.            |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Disclosure | Requires container label for blood and     |
| 606.121   |            | blood components by all blood              |
|           |            | establishments.                            |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Disclosure | Requires an instruction circular,          |
| 606.122   |            | containing adequate directions for use, be |
|           |            | available for distribution if the product  |
|           |            | is intended for transfusion.               |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires that records of expedited         |
|           | ordkeeping | transfusions in life-threatening           |
| 6         |            | emergencies be maintained, to allow clear  |
| 06.151(e) |            | tracing of all steps in the collection,    |
|           |            | processing, compatibility testing, storage |
|           |            | and distribution, quality control, and     |
|           |            | transfusion reaction reports and           |
|           |            | complaints for each unit of blood and      |
|           |            | blood components.                          |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires that legible and indelible        |
|           | ordkeeping | contemporaneous records of each            |
| 606.160   |            | significant step be made and maintained    |
|           |            | for no less than 5 years.                  |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires that distribution and receipt     |
|           | ordkeeping | records be maintained to facilitate        |
| 606.165   |            | recalls, if necessary.                     |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Rec        | Requires records to be maintained of any   |
|           | ordkeeping | reports of complaints of adverse reactions |
| 6         |            | as a result of blood collection or         |
| 06.170(a) |            | transfusion, and a written report,         |
|           |            | including conclusions and followup, must   |
|           |            | be prepared and maintained.                |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Reporting  | Requires that fatal complications of blood |
|           |            | collection and transfusions be reported to |
| 6         |            | FDA as soon as possible and that a written |
| 06.170(b) |            | report shall be submitted within 7 days.   |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Reporting  | Requires blood establishments to notify    |
|           |            | consignees, within 72 hours, of repeatedly |
| 610.46(a) | Disclosure | reactive tests results so that previously  |
|           |            | collected blood and blood components are   |
|           |            | appropriately quarantined.                 |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Reporting- | Requires blood establishments to notify    |
|           |            | consignees of licensed, more specific test |
| 610.46(b) | Disclosure | results for HIV within 30 calendar days    |
|           |            | after the donor's repeatedly reactive      |
|           |            | test.                                      |
+-----------+------------+--------------------------------------------+
| 21 CFR    | Reporting- | Requires transfusion services not subject  |
|           |            | to Centers for Medicare and Medicaid       |
| 610.47(b) | Disclosure | Services regulations to notify physicians  |
|           |            | of prior donation recipients or to notify  |
|           |            | recipients themselves of the need for HIV  |
|           |            | testing and counseling.                    |
+-----------+------------+--------------------------------------------+

In addition to the CGMP's in part 606 (21 CFR part 606), there are
regulations in part 640 (21 CFR part 640) that require additional
standards for certain blood and blood components as follows: §§640.3(a),
640.4(a), 640.25(b)(4) and (c)(1), 640.27(b), 640.31(b), 640.33(b),
640.51(b), 640.53(c), 640.56(b) and (d), 640.61, 640.63(b)(3), (e)(1),
and (e)(3), 640.65(b)(2), 640.66, 640.71(b)(1), 640.72, 640.73, and
640.76(a) and (b), (21 CFR 640.3(a), 640.4(a), 640.25(b)(4) and (c)(1),
640.27(b), 640.31(b), 640.33(b), 640.51(b), 640.53(c), 640.56(b) and
(d), 640.61, 640.63(b)(3), (e)(1) and (e)(3), 640.65(b)(2), 640.66,
640.71(b)(1), 640.72, 640.73, and 640.76(a) and (b)). The information
collection requirements and estimated burdens for these regulations are
included in the part 606 burden estimates, as described in section 12,
below.

Under the statutory requirements contained in section 351 of the Public
Health Service Act (42 U.S.C. 262, Tab B), no blood, blood component, or
derivative may move in interstate commerce unless: (1) it is propagated
or manufactured and prepared at an establishment holding an unsuspended
and unrevoked license; (2) the product complies with regulatory
standards designed to ensure safety, purity, and potency; and (3) it
bears a label plainly marked with the product's proper name,
manufacturer, and expiration date. In addition, under the biologics
licensing and quarantine provisions in sections 351-361 of the Public
Health Service Act (42 U.S.C. 262-264, Tab B) and the general
administrative provisions of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 351-353, 355-360, and 371-374, Tab C), FDA has the authority
to issue regulations designed to protect the public from unsafe or
ineffective biological products and to issue regulations necessary to
prevent the introduction, transmission, or spread communicable diseases.
The CGMPs and related regulations implement FDA's statutory authority to
ensure the safety, purity, and potency of blood and blood components.
The "lookback" regulations are intended to help ensure the continued
safety of the blood supply by providing necessary information to users
of blood and blood components and appropriate notification of recipients
of transfusion at increased risk for transmitting HIV infection.

2.  **[How, By Whom, and the Purpose for Collecting This
    Information]{.underline}**

The information collection requirements in the CGMP regulations and
"lookback" requirements provide FDA with the necessary information to
perform its duty to ensure the safety purity, and potency of blood and
blood components. These requirements establish accountability and
traceability in the processing and handling of blood and blood
components and enable FDA to perform meaningful inspections. The
recordkeeping requirements serve preventative and remedial purposes, and
ensure that industry has the necessary information to perform the
"lookback" procedures. The disclosure requirements identify the various
blood and blood components and important properties of the product,
demonstrate that the CGMP requirements have been met, and facilitate the
tracing of a product back to its original source. Consignee notification
ensures that the prior collections of blood and blood components are
appropriately quarantined. Recipient notification provides an
opportunity for counseling, appropriate testing, early treatment and
precautions necessary to prevent further spread of the virus. The
reporting requirements inform FDA of any deviations that occur and that
may require immediate corrective action.

Without this information, FDA could not monitor industry procedures and
discharge its statutory responsibility for protecting the nation's
health.

**3. [Use of Technology to Reduce the Burden on the
Public]{.underline}**

Establishments may use computer tapes, discs, microfiche or microfilm in
lieu of hard copy records for the purpose of maintaining records.
Computers may be used for filing reports to FDA. Notification of
consignees can be accomplished by phone, fax, or mail. FDA is not aware
of any other improved technology to reduce the burden except that
unautomated blood establishments could reduce the time required to
maintain records with respect to input and retrieval by becoming
computerized.

**4. [Identification and Use of Duplicate Information]{.underline}**

FDA is the only agency that requests this information. There is no
similar kind of information available from any other source.

**5. [FDA's Efforts to Reduce Burden on Small Business]{.underline}**

FDA believes that its duty requires the equal application of the
regulations to all enterprises. The likelihood of contracting a
contagious disease from a unit of blood collected from a small blood
establishment is just as great as one collected from a large blood
establishment. Consequently, the CGMPs and "lookback" regulations must
apply equally to both small and large manufacturers to adequately
protect the nation's blood donors and recipients. While FDA does not
believe it can apply different standards with respect to statutory
requirements, FDA does provide special help to small businesses. CBER's
Office of Communication, Training and Manufacturer's Assistance provides
assistance to small businesses subject to FDA's regulatory requirements.

6.  **[Impact of Not Collecting This Information or Collecting
    Information Less Frequently]{.underline}**

The requirement of less frequent information collection would not
provide the information necessary for blood establishments to perform
the "lookback" procedures, and for FDA to monitor the establishment
procedures and assure the prevention of communicable disease. Records
are reviewed at the time of inspection for compliance with FDA
regulations and for any appropriate corrective action. Initial
preparation of SOPs is a one-time burden.

There are no technical or legal obstacles to reducing the burden.

**7. [Special Circumstances That Occur When Collecting This
Information]{.underline}**

There are no special circumstances for the collection of the information
requirements.

8.  **[Identification of Outside FDA Sources]{.underline}**

In accordance with 5 CFR 1320.8(d), a 60-day notice for public comment
on the information collection provisions was published in the **Federal
Register** of July 22, 2002 (67 FR 47817, Tab D). No comments were
received from the public.

**9. [Payment or Gifts Offered to Respondents]{.underline}**

FDA has not provided and has no intention to provide any payment or gift
to respondents.

**10. [Method of Ensuring Respondent Confidentiality]{.underline}**

The confidentiality of information received by FDA would be consistent
with the Freedom of Information (FOI) Act and the agency's regulations
under 21 CFR Part 20. After a FDA investigator completes a routine
inspection of a blood or blood component manufacturing establishment,
the completed report with the results of the inspection become public
information, available under the FOI Act. However, certain information,
such as donor and patient names, for example, is deleted from any
information released by FDA under the FOI Act and FDA regulations.

**11**. **[Use of Sensitive Questions]{.underline}**

Establishments as part of the donor screening process for blood
collection must ask questions of sensitive nature. These questions are
used to evaluate the suitability of a donor. Donors not meeting certain
criteria are deferred from donating. This information is necessary to
help prevent the transmission of communicable diseases and protect
public health. These records are maintained by the establishment and may
be reviewed by FDA during an inspection.

**12. [Burden Hours and Costs Associated With This Information
Collection ]{.underline}**

The estimated annual burden for this information collection is 335,346
hours.

+-------------+----------+------------+----------+---------+--------+
| #           |          |            |          |         |        |
|  Table 1 -  |          |            |          |         |        |
| Estimated A |          |            |          |         |        |
| nnual Repor |          |            |          |         |        |
| ting Burden |          |            |          |         |        |
+-------------+----------+------------+----------+---------+--------+
| 21 CFR      | No. of   | Annual     | Total    | Hours   | Total  |
| Section     | Res      | Frequency  | Annual   | per     | Hours  |
|             | pondents | per        | R        | R       |        |
|             |          | Response   | esponses | esponse |        |
+-------------+----------+------------+----------+---------+--------+
| 60          | 70       | 1          | 70       | 20      | 1,400  |
| 6.170(b)^1^ |          |            |          |         |        |
+-------------+----------+------------+----------+---------+--------+
| 610.46(a)   | 1,041    | 20         | 21,000   | 0.17    | 3,570  |
+-------------+----------+------------+----------+---------+--------+
| 610.46(b)   | 1,041    | 20         | 21,000   | 0.17    | 3,570  |
+-------------+----------+------------+----------+---------+--------+
| 610.47(b)   | 166      | 0.7        | 116      | 1       | 116    |
+-------------+----------+------------+----------+---------+--------+
| ### Total   |          |            |          |         | 8,656  |
+-------------+----------+------------+----------+---------+--------+

> ^1^The reporting requirement in §640.73, which addresses the reporting
> of fatal donor reactions, is included in the estimate for §606.170(b).

+-----------+----------+-----------+------------+---------+----------+
| # Ta      |          |           |            |         |          |
| ble 2 - E |          |           |            |         |          |
| stimated  |          |           |            |         |          |
| Annual Re |          |           |            |         |          |
| cordkeepi |          |           |            |         |          |
| ng Burden |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 21 CFR    | No. of   | Annual    | Total      | Hours   | Total    |
| Section   |          | Frequency | Annual     | per     | Hours    |
|           | Recor    | per       | Records    | Record  |          |
|           | dkeepers | Reco      |            |         |          |
|           |          | rdkeeping |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 606.      | 249^4^   | 1         | 249        | 24      | 5,976    |
| 100(b)^1^ |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 6         | 249^4^   | 10        | 2,490      | 1       | 2,490    |
| 06.100(c) |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 606.      | 67^5^    | 5         | 335        | 0.5     | 168      |
| 110(a)^2^ |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 6         | 249^4^   | 12        | 2,988      | 0.083   | 248      |
| 06.151(e) |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 6         | 249^4^   | 2,169     | 540,000    | 0.5     | 270,000  |
| 06.160^3^ |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| 606.165   | 249^4^   | 2,169     | 540,000    | 0.083   | 44,820   |
+-----------+----------+-----------+------------+---------+----------+
| 6         | 249^4^   | 12        | 2,988      | 1       | 2,988    |
| 06.170(a) |          |           |            |         |          |
+-----------+----------+-----------+------------+---------+----------+
| Total     |          |           |            |         | 326,690  |
+-----------+----------+-----------+------------+---------+----------+

^1^The recordkeeping requirements in §§640.3(a)(1), 640.4(a)(1), and
640.66, which address the maintenance of SOPs, are included in the
estimate for §606.100(b).

^2^The recordkeeping requirements in §640.27(b), which address the
maintenance of donor health records for the plateletpheresis, are
included in the estimate for §606.110(a).

^3^The recordkeeping requirements in §§640.3(a)(2), 640.3(f),
640.4(a)(2), 640.25(b)(4) and (c)(1), 640.31(b), 640.33(b), 640.51(b),
640.53(b) and (d), 640.61, 640.63(b)(3), (e)(1), and (e)(3),
640.65(b)(2), 640.71(b)(1), 640.72, and 640.76(a) and (b), which address
the maintenance of various records, are included in the estimate for
§606.160.

^4^5 percent of CMS and FDA-registered blood establishments (0.05 x
4,890).

^5^5 percent of pheresis establishments (1,349).

Based on FDA's registration system, there are approximately 2,841
registered blood establishments inspected by FDA. Of these 2,841
establishments, approximately 1,349 perform pheresis, approximately
1,041 annually collect 27 million units of Whole Blood, blood components
including Source Plasma, and Source Leukocytes and are required to
follow FDA "lookback" procedures, and approximately 166 are registered
transfusion services that are not subject to Centers for Medicare and
Medicaid Services (CMS) "lookback" regulations. Based on CMS records
there are an estimated 4,980 transfusion services.

The following reporting and recordkeeping estimates are based on
information provided by industry, CMS, and FDA experience. In table 1 of
this document, we estimate that there are approximately 3,500 repeat
donors that will test reactive on a screening test for HIV. We estimate
that each repeat donor has donated two previous times and an average of
three components were made from each donation. Under §§610.46(a) and
(b), this estimate results in 21,000 (3,500 x 2 x 3) notifications of
the HIV screening test results to consignees by collecting
establishments for the purpose of quarantining affected blood and blood
components, and another 21,000 (3,500 x 2 x 3) notifications to
consignees of subsequent test results. Under §606.110(b), licensed
establishments submit supplements to their biologics license
applications to request prior CBER approval of plasmapheresis donors who
do not meet donor requirements. The information collection requirements
for §606.110(b) are reported under OMB control number 0910-0338.

In table 2 of this document, the recordkeeping chart reflects the
estimate that 95 percent of the recordkeepers, which collect 98 percent
of the blood supply, had developed SOPs as part of their customary and
usual business practice. Establishments may minimize burdens associated
with CGMP and related regulations by using model SOPs developed by
industries' accreditation organizations. These accreditation
organizations represent almost all registered blood establishments.

The development of labels is a one-time burden. The container labels
have been standardized and are sold commercially. The label is only
customized for the firm's name and address. In addition, the instruction
circular is printed by major blood banking associations, ARC, AABB, and
ABC, and are sold at minimal cost to the firms. The circulars are
updated annually usually die to new industry information. Therefore, no
burden is imposed by FDA regarding the labeling and disclosure
regulations (§§606.121 and 606.122) and Uniform Blood Labeling
Guideline.

#### Cost to Respondents

The estimated annual cost to respondents is \$14,084,532. This cost is
based on a pay rate of \$28/hour for a medical technologist (MT), who is
responsible for recording donor, quarantine, testing, and disposition of
information, notifying consignees of test results, and has the training
and skills to handle various recordkeeping requirements. The cost
estimate is also based on a supervisor, at a pay rate of \$38/hour who
is responsible for updating SOPs, recording donor information, and
notifying physicians of recipients or recipients of test results,
investigating, writing, and reporting a fatality, and a Medical Director
(MD), at a pay rate of \$61/hour, who is responsible for updating SOPs,
recording donor information, and notifying physicians of recipients or
recipients of test results, investigating, writing, and reporting a
fatality. These salary estimates include recordkeeping and
reporting-disclosure requirements that are performed by the MT,
supervisor, or MD, the cost/hour includes the average salary of the
three (\$42). These salary estimates include benefits but no overhead
costs.

+----------------+----------------+----------------+-----------------+
| # Cost         |                |                |                 |
| of Respondents |                |                |                 |
+----------------+----------------+----------------+-----------------+
| Activity       | No. of Hours   | Cost per Hour  | Total Cost      |
+----------------+----------------+----------------+-----------------+
| Recordkeeping  | 326,690        | \$42           | \$13,720,980    |
+----------------+----------------+----------------+-----------------+
| Reporting      | 8,656          | \$42           | \$363,552       |
+----------------+----------------+----------------+-----------------+
| Total          |                |                | \$14,084,532    |
+----------------+----------------+----------------+-----------------+

**13. [Annual Cost Estimate to Respondents]{.underline}**

There are no capital and start-up, or operation, maintenance and
purchase costs associated with the collection of information
requirements.

**14. [Annual Cost Estimate to FDA]{.underline}**

The estimated annualized cost to the Federal Government is \$1,407,720.
This estimate is based on a FDA investigator at an average grade scale
of GS-12/5 (\$33/hour) who performs on-site inspections. This cost
includes inspection of a facility, review of facility records, and
report preparation. The total estimated cost is also based on a GS-13/5
(\$40/hour) Consumer Safety Officer who compiles, reviews, and analyzes
fatality reports. These salary estimates include benefits but no
overhead costs.

+--------------------+------------+----------+------------+------------+
| # Annual Cost to   |            |          |            |            |
| Federal Government |            |          |            |            |
+--------------------+------------+----------+------------+------------+
| Activity           | Number of  | Hours    | Cost per   | Total Cost |
|                    |            | per      | Hour       |            |
|                    | R          |          |            |            |
|                    | espondents | Response |            |            |
+--------------------+------------+----------+------------+------------+
| Inspection         | 1,041      | 40       | \$33.00    | \          |
|                    |            |          |            | $1,374,120 |
+--------------------+------------+----------+------------+------------+
| Fatality Report    | 70         | 12       | \$40.00    | \$33,600   |
| Review             |            |          |            |            |
+--------------------+------------+----------+------------+------------+
| Total              |            |          |            | \          |
|                    |            |          |            | $1,407,720 |
+--------------------+------------+----------+------------+------------+

**15. [Changes from Previous Approval]{.underline}**

FDA is consolidating OMB control number 0910-0336 into 0910-0116. The
previous estimated total annual burden was 332,403 hours for 0910-0116
and 80,926 hours for 0910-0336. The current estimated total annual
burden is 335,346 hours. The overall decrease in burden is mostly
attributed to the revised estimates for the number of respondents.

**16. [Publishing the Results of This Information
Collection]{.underline}**

There are no results to publish for this information collection.

**17. [Reason for Not Displaying the OMB Approval Date]{.underline}**

FDA is not seeking approval to exempt display of the expiration date for
OMB approval.

**18. [Explanations to Section 19, "Certification for Paperwork
Reduction Act Submissions]{.underline}**

There are no exceptions to Item 19 of OMB Form 83-I.