[OMB INFORMATION COLLECTION]{.underline}

## SUPPORTING STATEMENT

0910-0308

Adverse Experience Reporting for Licensed Biological Products, and
General Records

**[JUSTIFICATION]{.underline}**

**1. [Circumstances Making the Collection of Information
Necessary]{.underline}**

The Food and Drug Administration (FDA) is requesting an extension of OMB
control No. 0910-0308 and OMB approval of the information collection
requirements in 21 CFR 600.12, 600.80, 600.81, and 600.90 (Tab A),
listed below:

+------------------+------------+--------------------------------------+
| 21 CFR           | Reporting  | Requires the licensed manufacturer   |
| 600.80(c)(1)     |            | to report each adverse experience    |
|                  |            | that is both serious and unexpected, |
|                  |            | regardless of source, as soon as     |
|                  |            | possible but in any case within 15   |
|                  |            | working days of initial receipt of   |
|                  |            | the information.                     |
+------------------+------------+--------------------------------------+
| 21 CFR           | Reporting  | Requires the licensed manufacturer   |
| 600.80(c)(2)     |            | to report all adverse experiences in |
|                  |            | a narrative summary, not reported    |
|                  |            | under paragraph (c) (1) (i) at       |
|                  |            | quarterly intervals for 3 years from |
|                  |            | the date of issuance of the product  |
|                  |            | license, and then at annual          |
|                  |            | intervals.                           |
+------------------+------------+--------------------------------------+
| 21 CFR 600.80(e) | Reporting  | Requires the licensed manufacturers  |
|                  |            | to submit a 15-day Alert report      |
|                  |            | obtained from a postmarketing        |
|                  |            | clinical study only if there is a    |
|                  |            | reasonable possibility that the      |
|                  |            | product caused the adverse           |
|                  |            | experience.                          |
+------------------+------------+--------------------------------------+
| 21 CFR 600.81    | #          | Requires the licensed manufacturers  |
|                  |  Reporting | to report semiannually the quantity  |
|                  |            | of the product distributed under the |
|                  |            | product license, including the       |
|                  |            | quantity distributed to              |
|                  |            | distributors.                        |
+------------------+------------+--------------------------------------+
| 21 CFR 600.90    | Reporting  | Requires the licensed manufacturer   |
|                  |            | to submit a waiver request with      |
|                  |            | supporting documentation for waiving |
|                  |            | the requirements under 21 CFR 600.80 |
|                  |            | and 600.81.                          |
+------------------+------------+--------------------------------------+
| 21 CFR 600.80(i) | Rec        | Requires records of all adverse      |
|                  | ordkeeping | experiences to be maintained for ten |
|                  |            | years.                               |
+------------------+------------+--------------------------------------+
| 21 CFR           | Rec        | Requires records of each step in the |
| 600.12(a), (c),  | ordkeeping | manufacture and distribution of a    |
| (d) & (e)        |            | product to be maintained for a       |
|                  |            | prescribed period of time.           |
+------------------+------------+--------------------------------------+
| 21 CFR           | Rec        | Requires records to be maintained    |
| 600.12(b)(2)     | ordkeeping | pertaining to the recall from        |
|                  |            | distribution of any product.         |
+------------------+------------+--------------------------------------+

Under the Public Health Service Act (42 U.S.C. 262, Tab B), FDA is
required to ensure the marketing and production of only those biological
products which are safe, pure, and potent. FDA must, therefore, be
promptly informed of all adverse experiences occasioned by the use of
licensed biological products. FDA promulgated the adverse experience
reporting requirements in 21 CFR §§600.80 and 600.81 to enable FDA to
take actions necessary for the protection of the public health in
response to reports of adverse experiences related to licensed
biological products. The licensed manufacturers are required to report
to FDA on all serious and unexpected adverse reactions regardless of the
source from which the manufacturer obtained the reaction information.
These reports are filed using the MedWatch Form FDA-3500A (approved
under OMB No.0910-0291, Tab C); or the Vaccine Adverse Experience
Reporting System Form (VAERS-1, Tab D). Section 321 of the National
Childhood Vaccine Injury Act (NCVIA) specifically addresses the waiver
of paperwork reduction in the implementation of this statute. A
manufacturer may also use an alternative report form provided the format
is equivalent to all elements of information specified in the designated
forms and the format is pre-approved by MedWatch or VAERS.

The general recordkeeping provisions under §600.12 require manufacturers
to maintain records of each step in the manufacture and distribution of
products. These requirements provide FDA with the necessary information
to help ensure the safety, purity, and potency of biological products.

**2. [Purpose and Use of the Information]{.underline}**

The primary purpose of FDA's adverse experience reporting (AER) system
is to flag potentially serious safety problems with licensed biological
products, focusing especially on newly licensed products. Although
premarket testing discloses a general safety profile of a new drug's
comparatively common adverse effects, the larger and more diverse
patient populations exposed to the licensed biological product provides,
for the first time, the opportunity to collect information on rare,
latent, and long-term effects. Reports are obtained from a variety of
sources, including patients, physicians, foreign regulatory agencies,
and clinical investigators. Information derived from the adverse
experience reporting system contributes directly to increase public
health protection because such information enables FDA to recommend
important changes to the product's labeling (such as adding a new
warning) and, when necessary, to initiate removal of a biological
product from the market and to assure the manufacturer has taken
adequate corrective action, if necessary. The semiannual distribution
report allows FDA to see the quantity, the lot number, and the dosage of
different products. This allows FDA to estimate more accurately the
incidence of a product's adverse effects in relation to the volume of
the product distributed.

The recordkeeping requirements serve preventative and remedial purposes
by assuring accountability and traceability in each step from the
manufacture to distribution and recall of products and by enabling FDA
to perform meaningful inspections. Without this information, FDA could
not monitor industry procedures and discharge its statutory
responsibility for protecting the nation's health.

**3. [Use of Information Technology and Burden Reduction]{.underline}**

Licensed manufacturers may use computers, tapes, microfiche or microfilm
in lieu of hard copy records for the purpose of maintaining records.
Computers may be used for filing distribution records. FDA is not aware
of any other improved technology to reduce the burden.

**4. [Efforts to Identify Duplication and Use of Similar
Information]{.underline}**

FDA is the only agency that requests this information. The required
information is not available from any other source.

**5. [Impact on Small Businesses or Other Small Entities]{.underline}**

FDA believes that the regulations should apply equally to all
enterprises. 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
Manufacturers Assistance provides guidance to small businesses
concerning regulatory requirements.

**6. [Consequences of Collecting the Information Less
Frequently]{.underline}**

Less frequent data collection would delay identification of biological
products believed responsible for adverse reactions including permanent
injuries and fatalities. Appropriate FDA action such as withdrawal from
the market or changes in labeling would also be delayed. However, FDA is
preparing to issue a proposed rule that would amend the expedited and
periodic safety reporting regulations for human drugs and biological
products to revise certain reporting formats as recommended by the
International Conference on Harmonization (ICH), to revise current
reporting requirements, to revise certain reporting time frames, and to
make other revisions to the regulations to enhance the quality of
suspected adverse drug reaction reports received by FDA.

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

**7. [Special Circumstances Relating to the Guidelines of 5 CFR
1320.5]{.underline}**

The licensed manufacturers are required to submit to FDA a 15-day Alert
report for each serious and unexpected adverse experience. This
requirement enables FDA to promptly investigate, and when necessary,
initiate corrective action to protect the public from potential adverse
product interactions.

**8. [Comments in Response to the Federal Register Notice and Efforts to
Consult Outside ]{.underline}**

**[Agency]{.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 September 25, 2000, (65 CFR 57612, Tab E). *[No comments
were received from the public]{.underline}.*

**9. [Explanation of Any Payment or Gift to Respondents]{.underline}**

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

**10. [Assurance of Confidentiality Provided to
Respondents]{.underline}**

The confidentiality of information received by FDA is consistent with
the Freedom of Information Act and the agency's regulations under 21 CFR
Part 20 which prohibit FDA from releasing to the public the names of
patients, individual reporters, health care practitioners, hospitals,
and any geographical identifiers.

**11. [Justification for Sensitive Questions]{.underline}**

Questions of a sensitive nature are not applicable to this information
collection.

**12. [Estimates of Hour Burden Including Annualized Hourly
Costs]{.underline}**

The estimated annual burden for this information collection is 268,803
hours.

  -------------- ------------- ----------- ----------- ----------- -----------
  Estimated                                                        
  Annual                                                           
  Reporting                                                        
  Burden                                                           

  21CFR Section  No. of        Annual      Total       Hours Per   Total Hours
                 Respondents   Frequency   Annual      Response    
                               per         Responses               
                               Response                            

  600.80(c)(1) & 78            46.95       3,662       1           3,662
  600.80(e)                                                        

  600.80(c)(2)   78            169.72      13,238      1           13,238

  600.81         78            6.44        502         1           502

  600.90         4             1           4           1           4

  TOTAL                                                            
  -------------- ------------- ----------- ----------- ----------- -----------

Respondents to this collection of information are manufacturers of
biological products. In FY99, there were approximately 79 licensed
manufacturers. This number excludes those manufacturers who produce
blood and blood components and in-vitro diagnostic licensed products
because they are specifically exempt from the regulations. However, not
all manufacturers may have any submissions in a given year and some may
have multiple submissions. FDA received 4 waiver requests under §600.90,
of which 1 was approved for exemption of the AER requirements. In FY99,
there were an estimated 3,662 15-day alert reports, 13,238 periodic
reports, and 502 distribution report submitted to FDA. The number of
15-day alert report for postmarketing studies as stated in §600.80(e)
was minimal and is included in the total number of 15-day alert reports.
The hours per response are based on FDA experience. The burden hours
required to complete the MedWatch Form for §600.80(c)(1), (e) and (f)
are reported under OMB Control No. 0910-0291.

  --------------- --------------- --------------- ----------- --------- ---------
  Estimated                                                             
  Annual                                                                
  Recordkeeping                                                         
  Burden                                                                

  21 CFR Section  No. Of          Annual          Total       Hours per Total
                  Recordkeepers   Frequency of    Annual      Record    Hours
                                  Recordkeeping   Records               

  600.12          111             58.1            6,446       32        206,272

  600.12(b)(2)    343             3.4             1,176       24        28,224

  600.80(i)       79              213.92          16,900      1         16,900

  TOTAL                                                                 
  --------------- --------------- --------------- ----------- --------- ---------

There are approximately 343 licensed manufacturers of biological
products. However, the number of recordkeepers listed for §600.12(a)-(e)
excluding (b)(2) is estimated to be 111. This number excludes
manufacturers of blood and blood components, because their burden hours
for recordkeeping have been reported under §606.160 in OMB Control No.
0910-0116. The recordkeeping burden is based on the number of lots
released (6,446), the number of recalls made (1,176) and the total
number of AER reports received (16,900) for FY99. The hours per record
are based on past FDA experience.

[Cost to Respondents]{.underline}

The estimated annualized cost to the respondents is \$7,526,484. This
cost is based on a pay rate of \$28 per hour for a mid-level
professional who has the training and skills to handle the various
reporting and recordkeeping requirements. This salary estimate includes
benefits but no overhead costs.

+-----------------+-----------------+-----------------+-----------------+
| Cost to         |                 |                 |                 |
| Respondents     |                 |                 |                 |
+-----------------+-----------------+-----------------+-----------------+
| Activity        | Number of Hours | Cost per Hour   | Total Cost      |
+-----------------+-----------------+-----------------+-----------------+
| # Reporting     | 17,407          | \$28            | \$487,396       |
+-----------------+-----------------+-----------------+-----------------+
| # Recordkeeping | 251,396         | \$28            | \$7,039088      |
+-----------------+-----------------+-----------------+-----------------+
| # TOTAL         |                 |                 |                 |
+-----------------+-----------------+-----------------+-----------------+

**13. [Estimate of Other Total Annual Cost Burden to Respondents or
Record-keepers]{.underline}**

There is no capital and start-up, or operation, maintenance and purchase
costs associated with

the collection of information requirements.

**14. [Annualized Costs to the Federal Government]{.underline}**

The estimated annual cost to the government is \$259,364. This figure is
based on a GS-6/5 Consumer Safety Technician, at a pay rate of \$17 per
hour, who is responsible for triage of the report. This figure is also
based on a GS-13/5 Consumer Safety Officer, at a pay rate of \$40 per
hour, who is responsible for reviewing the reports.

+------------+--------------+-----------------+------------+----------+
| Annual     |              |                 |            |          |
| Cost to    |              |                 |            |          |
| Federal    |              |                 |            |          |
| Government |              |                 |            |          |
+------------+--------------+-----------------+------------+----------+
| Activity   | Number of    | Hours per       | Cost per   | Total    |
|            | Report       | Report          | Hour       | Cost     |
+------------+--------------+-----------------+------------+----------+
| Report     | 17,407       | 0.1             | \$17       | \$29,592 |
| Triage     |              |                 |            |          |
+------------+--------------+-----------------+------------+----------+
| Report     | 17,407       | 0.33            | \$40       | \        |
| Review     |              |                 |            | $229,772 |
+------------+--------------+-----------------+------------+----------+
| # TOTAL    |              |                 |            |          |
+------------+--------------+-----------------+------------+----------+

**15. [Explanation of Program Changes or Adjustments]{.underline}**

The estimated total annual burden for the AER information collection
requirements was 346,891 hours in 1998. The current decrease to 268,803
burden hours is mostly attributed to the revised total annual records
under §600.12, and the revised estimated hours per response under
§600.80(c)(2).

**16. [Plans for Tabulation and Publication and Project Time
Schedule]{.underline}**

There are no tabulated results to publish for this information
collection.

**17. [Reason(s) Display of OMB Expiration Date is
Inappropriate]{.underline}**

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

**18. [Exception to Certification for Paperwork Reduction Act
Submissions]{.underline}**

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