The document discusses common regulatory issues and challenges with electronic submissions to the FDA's Electronic Submissions Gateway (ESG). It notes that while ESG streamlines submissions, users often face validation issues that result in failed submissions and resubmissions. This increases costs and processing time. The document presents a case study that used process improvement methods to increase a vendor's SPL submission success rate from 54% to over 98%. It concludes that analyzing submission failures across all FDA centers could further improve the electronic submission process.

1. Common regulatory issues and
challenges in dealing with
eSubmissions
through FDA electronic
submissions gateway
Jayprakash
Sr. Project Leader
Nov. 2012

2. Disclaimer
While every effort is made by the author to
ensure that all the information provided is
accurate and solely for the information
purpose only, the author accepts no
liability for the consequences of any
actions taken on the basis of the
information provided. Any views or opinions
presented in this research study are solely
those of the author and do not necessarily
represent any company or agency.

3. Introduction
 The Food and Drug Administration (FDA) Electronic Submissions
Gateway (ESG) is an Agency-wide solution for accepting electronic
regulatory submissions.
 Implementation of FDA ESG into production in May, 2006.
 In 2006 itself, FDA ESG received 58,664 electronic submissions for
AERS, CDER, CBER & CDRH Centers.
 Improves cost savings, reduce resource requirements, and time
efficiencies for both Sponsors and the Agency.
 OC started receiving SPL submissions from 2008 and became a
mandate after 30 June 2009.
 OC received a total of 173,732 electronic submissions till now.

4. Constraints
 The FDA ESG does not review submissions and only automatically
routes documents to the chosen Office or Center.
 Users often face common validation issues due to either user
discrepancy or new FDA guidelines.
 A failed submission creates a chain of resubmissions.
 Delays the product approval causing severe impact on the business
of the company.
 A failed electronic submission requires additional resources to fix it.
 Resubmission adds up additional cost to the company.
 Multiple resubmissions from various users increase additional traffic
on the gateway which impacts its efficiency and consistency.

5. Case Study
 To identify the factors which cause validation errors during electronic
submissions made to OC for SPL documents.
 Aim was to take preventive and corrective actions (CAPA) and a
control plan to achieve at least 95% success rate for electronic
submissions made to FDA ESG OC Center during first attempt.
 Project Charter
BUSINESS CASE
 This company submitted total 119 Structured Product Labeling documents to FDA ESG from Oct
2009 to Mar 2011, Out of which 65 passed and 54 SPL documents failed the FDA ESG Validation.
 This higher ratio of failures is affecting the SPL conversion Turnaround time, Productivity,
Customer Satisfaction and may result in Loss of Services Contract.
PROBLEM STATEMENT
 The SPL Consulting Team has received numerous grievances from the customer regarding
frequent SPL failures at FDA ESG and delayed approvals for their product.
 Failure to create/convert total compliant SPL ,negatively impacts customer satisfaction and
increases cost to both the company business and the customer.
GOAL STATEMENT
 To improve the SPL submission success rate from 54.62% to 95% by Dec 2011 and reduce the
SPL conversion Turnaround time to 5 days.

6. Case Study
 The current Sigma value (Z) before the implementation of the Green
Belt project.
Details Symbols Values
Defect opportunities per Unit O = 1
Number of units processed N = 119
Total number of defects made
D = 54
(include defects made and later fixed)
Defects Per Opportunity DPO = D/N*O 0.453781513
Yield (1-DPO)*100 54.62
Process Sigma (Short term) Z = 1.6

7. Case Study
 The number of errors after implementation of the Green Belt Project
was reduced drastically.
STATISTICAL PROCESS CONTROL – SPL DOCUMENT TYPE
Before After
SPL Document Types SPL Document Types
Failed Total Submitted Failed Total Submitted
79
76
41
29
22
14 12
9
4 2
0 0
LCR ERF SPL LCR ERF SPL

8. Case Study
 The % of defective items was reduced by 96% from 45.38% to 1.77%.
BINOMIAL CAPABILITY COMPARISON

9. Case Study
 By implementing the new proposed solution the process sigma
improved from 1.6 Sigma to 3.6 sigma.
Details Symbols Before After
Defect opportunities per Unit O= 1 1
Number of units processed N= 119 113
Total number of defects made
D= 54 2
(include defects made and later fixed)
Defects Per Opportunity DPO = D/N*O 0.453781513 0.017699
Yield (1-DPO)*100 54.62 98.23
Process Sigma (Short term) Z= 1.6 3.6

10. Current Scope
 Six Sigma Green Belt Project was done only for the SPL submissions
made to OC by a Regulatory Compliance vendor.
 Submission made by all users to all the FDA Centers are prone to
much more issues.
 If all these submissions made to all FDA Centers are monitored and
assessed for submission failures, the scope for improvement will
definitely be massive.
 A total of 3,806,019 electronic submissions were made to FDA ESG
till now.
 In 2012 itself, 1,166,872 electronic submissions made to FDA ESG.

11. Submission Statistics
2006 - 2012
2006 2007 2008 2009 2010 2011 2012 Totals
Totals
AERS 55,156 159,562 252,614 300,672 472,142 557,917 595,182 2,393,245
CDER 1,639 11,175 24,797 45,510 69,739 93,503 88,367 334,730
CBER 294 1,504 2,557 4,483 5,588 6,397 5,736 26,559
CDRH 1,575 1,527 4,619 21,296 119,087 280,312 390,355 818,771
CVM 288 843 859 945 17,932 30,268 51,135
OC 188 16,275 48,232 55,676 53,361 173,732
CTP 5 223 348 520 1,096
MWP 1,138 2,530 2,361 6,029
ACA 53 53
GDUFA 669 669
Totals 58,664 174,056 285,618 389,100 717,094 1,014,615 1,166,872 3,806,019

12. Future Trends
 FDA ESG is the most advanced & busiest gateway. Scope to move to
the next level of electronic submissions going forward.
 With Artificial Intelligence, the role of FDA ESG can be enhanced to
handle complex validation rules and automate major of the review
system to process the electronic submission at much faster pace.
 With Auto Correction feature, FDA ESG will fix minor issues to save
time, effort and cost.
 FDA ESG Auto Renewal component will renew the recurring renewal
submissions and reduce load on the system.
 An integrated ESG can help the companies with single submission
multiple approvals for different countries.
 The performance reports based on each user with passed and failed
status can be introduced to help them assess their proficiency.

13. Conclusion
 The scope is wide open and confirms the issues focused are only the
tip of the iceberg.
 This electronic submission process needs more consideration and
shall be open for further analysis.
 Goal shall be to enhance all the electronic submissions made to FDA
ESG at 95 % success rate at the first attempt itself.
 Electronic submissions validated during first attempt will eliminate the
need for resubmissions.
 Companies can save on Cost, Effort & Time required to fix the failed
electronic submissions at FDA ESG.
 Lessen the burden on the gateway, increasing its efficiency and
consistency.

14. Courtesy
 FDA.gov :
http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/ucm1
10653.htm
 Professional Services Group – Virtify Inc. (http://www.virtify.com)
 Getting started with the FDA’s electronic submissions gateway -
(Regulatory Rapporteur – Vol 7, No 9, September 2010)

15. Questions & Answers
 Jayprakashreddy
 Reddyjayprakash