Common regulatory issues and challenges in dealing with

eSubmissionsthrough FDA electronic submissions gateway

JayprakashSr. Project Leader

Nov. 2012

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.

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.

Introduction

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.

Case Study

BUSINESS CASE

PROBLEM STATEMENT

GOAL STATEMENT

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.

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.

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.

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

Case Study

Details Symbols Values

Defect opportunities per Unit O = 1

Number of units processed N = 119

Total number of defects made(include defects made and later fixed)

D = 54

Defects Per Opportunity DPO = D/N*O 0.453781513

Yield (1-DPO)*100 54.62

Process Sigma (Short term) Z = 1.6

The current Sigma value (Z) before the implementation of the Green Belt project.

STATISTICAL PROCESS CONTROL – SPL DOCUMENT TYPE

Before After

LCR ERF SPL

49

41

14

29

76

SPL Document TypesFailed Total Submitted

LCR ERF SPL

0 0 2

12

22

79

SPL Document TypesFailed Total Submitted

Case Study

The number of errors after implementation of the Green Belt Project was reduced drastically.

Case Study

BINOMIAL CAPABILITY COMPARISON

The % of defective items was reduced by 96% from 45.38% to 1.77%.

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(include defects made and later fixed)

D = 54 2

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

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.

Submission Statistics

2006 - 2012 Totals

2006 2007 2008 2009 2010 2011 2012 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

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.

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.

Courtesy

FDA.gov : http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/ucm110653.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)

Questions & Answers

Thank You

Jayprakashreddy

Reddyjayprakash