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Work Performed: Understanding of the FDA Methodology

Table of Contents

Evaluation and Study Assumptions

Figure 1 below shows the PDUFA IV Workload Adjuster (also referred to as the baseline model) with the adjustments for changes in review activities.

Application

Column 1

Column 2a

Column  2b Adjustment for changes in Review Activity

Column 2c is Column 2a increased by Column 2b

Column 3

Column 4

Column 5

Type

5-Year Avg. Base Years

Latest 5-Year Avg.

Percent Change

Weighting Factor

Weighted % Change

 

2002-2007

2003-2008

 

 

 

NDA’s/BLA’s

123.8

128.4

-0.55%

127.7

3.1%

33.3%

1.05%

Active Commercial IND’s

5,755.8

5,897.6

0.39%

5,920.6

2.9%

45.2%

1.31%

Efficacy Supplements

163.4

173

NA

173.3

5.9%

8.3%

0.49%

Manufacturing Supplements

2,589.2

2,616.2

NA

2,616.2

1.0%

13.2%

0.14%

FY 2009 Workload Adjuster With Adjustment for Changes in review Activities

2.98%

Figure 1 – PDUFA IV Workload Adjuster with Adjustments for Changes in Review Activities[1]

Column 1 displays the baseline 5-year averages calculated based on the number of submissions for each application type for the FY 2002 through FY 2007.

Column 2a displays the current 5-year averages calculated based on the number of submissions for each application type for the FY 2003 through FY 2008.

Column 2b displays the percentage change in workload for the NDA/BLA and IND application types, which are also referred to as the adjustments for changes in review activities.

Column 2c represents the adjusted current 5-year averages from Column 2a after the adjustments in Column 2b are applied to Column 2a. (Note that only the 5-year averages for the NDA/BLA and IND application types change.)

Column 3 represents the percent change in workload from Column 1 to Column 2c.

Column 4 displays the appropriate weighting factors that are applied to each application type. Background information on how the weighting factors are calculated is summarized as follows:

  • The PDUFA IV Workload Adjuster utilizes time reporting data to capture the level of effort utilized during the process for the review of human drug applications. The Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) both conduct time reporting surveys to gather information on the level of effort utilized for the process for the review of human drug applications.[2]
  • The CDER and CBER time reporting data is also used by FDA in generating estimates of standard costs for the process of human drug review. The standard cost model generates estimates of the average processing costs for each application type.[3] These standard cost estimates are then used to create weighting factors for each application type included in the PDUFA IV Workload Adjuster.
  • The weighting factors displayed are also the average weights over the most recent 5-year period.

Column 5 displays the workload adjustment for each application type. These weighted percentages are calculated by multiplying the weighting factor in Column 4 by the percent change in workload in Column 3. The sum of the weighted percentages for each application type shown in Column 5 represents the final adjustment in workload of 2.98% for FY 2009.

 

Figure 2 below depicts a flow of the PDUFA IV Workload Adjuster that is shown in Figure 1. The enlarged box with a bolded border represents the adjustments for changes in review activities (Column 2b), which is the specific area of study within the scope of this project.[4]

 

Figure 2 of PDUFA IV Workload Adjuster

Figure 2 – Flow of PDUFA IV Workload Adjuster with Adjustments for Changes in Review Activities

Figure 2: 508-Compliant Narrative

Based on our understanding of the FDA methodology for the PDUFA IV Workload Adjuster with adjustments for changes in review activities, five specific review activities were identified by FDA as the primary drivers contributing to observed increases in the application review workload over the years. These specific review activities are not an exhaustive list of application-review related activities; however they are able to be measured in terms of relative level of effort. The additional work necessary to perform these specific review activities was not captured in the PDUFA III Workload Adjuster. The five review activities and the associated application types are:

New Drug Applications (NDAs) / Biologics License Applications (BLAs)

  1. Labeling Supplements: The FDA reviews the labeling supplements for human prescription drug and biological products to assess pertinent information about the appropriate use of drugs.
  2. Annual Reports: The review of annual reports submitted for NDAs/BLAs from sponsors on an annual basis.[5]
  3. NDA/BLA Meetings Scheduled: Meetings scheduled during the review of NDAs/BLAs.

Investigational New Drug (IND) Applications

  1. Special Protocol Assessments (SPAs): The FDA reviews the SPAs submitted by sponsors to assess whether they are adequate to meet scientific and regulatory requirements identified by the sponsors. Three types of protocols related to PDUFA products are eligible for this special protocol assessment under the PDUFA goals: Animal Carcinogenicity protocols; Final Product Stability protocols; and Clinical protocols.
  2. IND Meetings Scheduled: Meetings scheduled during the review of IND applications.

The adjustments for changes in review activities (Column 2b in Figure 1) were calculated by first calculating the individual activity factors for each of the review activities listed above. The activity factor is a product of the percent change in level of effort and the average time weighting factor. Once the activity factor was calculated for each individual review activity component, the percentages were totaled by application type to derive the final adjustments for changes in review activities, as percentages. The details of the calculation are described below:

  • Step 1: To obtain the percent change in level of effort for each review activity component, the current and base 5-year average counts for the review activity were divided by the current and base 5-year average submission counts for the corresponding application type. For example, the most recent 5-year average number of Labeling Supplements was divided by the most recent 5-year average number of new NDA/BLA submissions; the most recent 5-year average number of SPAs was divided by the most recent 5-year average number of Active INDs. Next, the percentage change for the current year was calculated relative to the base year, for each review activity component.
  • Step 2: To obtain the average time weighting factor for each review activity component, the percent of CDER and CBER time spent on each review activity was multiplied by the percent of total CDER and CBER time spent on the corresponding application type, for each fiscal year. For example, ([% of CDER time spent on Labeling Supplements] x [% of total CDER NDA/BLA time]) + [% of CBER time spent on Labeling Supplements] x [% of total CBER NDA/BLA time]) = Time Weighting Factor for Labeling Supplements (as a percentage). The average time weighting factor for the current year was calculated by computing the average value for each review activity component for the most recent 5-year period.
  • Step 3: The percentages resulting from Step 1 and Step 2 were multiplied to produce the final activity factor for each review activity component.
  • Step 4: The activity factors for Labeling Supplements (-0.09%), Annual Reports (-0.07%), and NDA/BLA Meetings Scheduled (-0.39%) were added together to generate the total -0.55% adjustment for changes in review activities for NDAs/BLAs. The activity factors for SPAs (0.09%) and IND Meetings Scheduled (0.30%) were added together to generate the total 0.39% adjustment for changes in review activities for INDs.

The remainder of this report discusses the evaluation, study, and assessment of these adjustments for changes in review activities.



[1]Federal Register/ Volume 73, Number 149, "Food and Drug Administration, Prescription Drug User Fee Rates for Fiscal Year 2009" pg. 45020, Table 4, August 1, 2008. (Column 2c for Efficacy Supplements was changed to reflect 173 and Manufacturing Supplements was changed to reflect 2616.2; Per our evaluation and discussion with the FDA, 173.3 and 2516.2, respectively, were misprinted in the Federal Register.
[2] CDER employs the Time Reporting System (TRS) to collect data on time spent on the four application types listed above. CDER collects information from two four-week periods at two different points during the year, for a total of 8 weeks of data. CBER employs the Resource Reporting System (RRS) to collect data on the time spent on the four applications types (NDA/BLAs, Active Commercial IND’s, Efficacy Supplements, and Manufacturing Supplements). CBER collects information from one pay period (two weeks) per quarter, for a total of 8 weeks of data. The distribution of time reported is allocated through FTEs to each of the offices that are directly responsible for reviews. For both centers, the time reported represents the level of effort expended on each review activity based on a set of activity codes put forth by FDA. (These activity codes represent the different types of review activities associated with the process for the review of human drug applications as defined in PDUFA.) Both centers use the time related to the direct review of applications as a driver to allocate the time of the offices that perform functions that indirectly support the process for the review of human drug applications.
[3] The process costs are based on obligation amounts that are obtained from the Office of Financial Management (OFM) and distributed, based on time reporting data, to various application types.
[4] A more detailed diagram illustrating our understanding of the PDUFA IV Workload Adjuster is included in Appendix A.
[5] Annual reports for Abbreviated New Drug Applications (ANDAs) were not included in the PDUFA IV Workload Adjuster with adjustments for changes in review activities.

 

  Figure 2 – Flow of PDUFA IV Workload Adjuster with Adjustments for Changes in Review Activities

The PDUFA IV Workload Adjuster process is outlined in Figure 2, based on the table shown in Figure 1. This process begins with Column 1, which represents the base 5-year averages that are calculated using the number of submissions for each application type, from FY 2002 through FY 2007. Concurrently, the values in Column 2a represent the current 5-year averages, and are calculated based on the number of submissions for each application type, from FY 2003 through FY 2008. Next, Column 2b, which represents the adjustment for percentage change in certain workload factors that apply to NDA/BLAs and INDs are calculated. These percentages are referred to as the adjustments for changes in review activities. Column 2c represents the adjusted current 5-year averages in column 2a after the adjustments for changes in review activities in Column 2b are applied. (Note that only the 5-year averages for the NDA/BLA and IND application types change in Column 2c.) Column 3 is derived by subtracting the values in Column 1 from the value in Columns 2c for each line, and then dividing the result by the by the values by Column 1, and represents the percent change in workload for each application type. The weighting factor values in Column 4 are calculated based on estimates of the standard cost to review each submission type. Values in Column 5 are calculated from data in Columns 3 and 4 to determine the final weighted percent change in workload for each application type. Values in Column 5 are also summed across application types to generate a final Workload Adjuster value.

Return to Figure 2

Evaluation and Study Assumptions