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GDUFA Establishment Fees: Are they Fair to the Generic Industry?

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I would like to start by stating these are the observances we have seen and by no means do I have a definitive solution for the problem.  I believe GDUFA (Generic Drug User Fee Amendments of 2012) and the overall system can be effective as it was with PDUFA (Prescription Drug User Fee Act) however I believe the system will require some tweaking.

With the recently announced and rapidly approaching deadline for GDUFA Establishment fees on March 4, 2013, the smaller companies and frequent users of contract manufacturers organizations (CMOs) are quickly realizing that this is completely changing the industry and the competitive landscape for Generic products especially small contract manufacturing organizations (CMOs) that are quickly deciding that the extra fees is too great to spend.  This creates difficult situations between ANDA applicants and the potential CMOs.  In the current system for Fiscal Year 2013 an ANDA filer spends $51,520 as a one-time ANDA fee, however the CMO if there is one spends $175,389 if domestic and $190,389 if foreign per year.  With the current average approval timelines that is between $500,000 and $600,000 in fees assuming the fees do not change.  Looking at a small CMO that has one ANDA submitted, the facility fees are 10x the ANDA fee.  This is not insignificant by any means.

This fee structure creates a huge burden on a small CMO especially one that is entering generic drug manufacturing for the first time.  We are finding that many small CMOs that are currently not manufacturing generic products today are refusing to pay the fees as it will be very difficult to recoup the fees since there is no manufacturing going on during these years.  Also this situation is very scary for a generic company that uses a CMO because if the CMO refuses to pay at any time in the review process the ANDA will be killed.  This can create many sleepless nights.

There are many similarities in the structure between PDUFA and GDUFA and there are some striking differences as shown in the table below.  Here we are focusing on the Drug product side and not the API side. Also we acknowledge that the review of an ANDA is nowhere near the same as the review of a NDA.

Comparison of PDUFA and GDUFA Fees 








$1,958,800 (with clinicals)

$979,400 (without clinicals)       

$979,400 (with clinicals




$25,760 (PAS)


$ 526,500

$175,389 if domestic                    

$190,389 if foreign





In looking at the fees above for an application the fees for NDAs are much larger. Also in looking at the fees at first glance you would say the same holds true for Establishments, however when you take into account these fees are yearly and there are currently significant differences between PDUFA and GDUFA timelines these fees quickly become almost the same and in some instances higher for generic products.  Finally you will notice that GDUFA has no yearly fee for approved products.

Looking at this, the primary difference between PDUFA and GDUFA is that PDUFA allocates the fees based on the number of submissions and products you are currently selling while GDUFA does not take into account the number of applications a company has approved as there is no fee for the product.  However each ANDA requires yearly submissions such as Annual Reports, Safety Reporting, CBE's, each of these require FDA resources with no collection mechanism.  GDUFA fees are predominately paid by companies that utilize numerous manufacturing sites at different locations and gives benefits to companies that have large campuses, as with the current set up a campus has only one fee.  This fee is the same as a small manufacturing facility with one product.  I will agree that both facilities require Agency resources however the amount of resources are not on the same level.

I believe that the fees should be weighted based similar to PDUFA with a product based yearly fee.  This would create equality among the various sized companies relating the fees to not only the number of products filed but also the number of products approved.

Please feel free to provide your comments.  This way we can see if we can possibly change the system.

Delayed ANDA approvals cost thousands per day!


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 Regulatory Timelines are critical!!


Don’t try to cut corners when choosing your regulatory service provider, you may be able to save a few bucks upfront but it could end up costing you millions, see below


Average ANDA approval times are approaching 31 months


The cost of hiring a service provider with less experience can create significant delays


Many companies we deal with chooses interesting generic products with expected profits in the millions; each business day these product approvals are delayed will cost you significant dollars


$1,000,000 product will cost you $5,000 per business day

$5,000,000 product will cost you $25,000 per business day

$10,000,000 product will cost you $50,000 per business day

$20,000,000 product will cost you $100,000 per business day


Custopharm filed the first eCTD ANDA in 2004 and we have filed well over 150 since, we respond to over 100 deficiencies each year


You can trust Custopharm, we are knowledgeable and experienced and our prices are fair


We are easy to deal with - privately held with no outside investors, we still believe in customer service



Contact Dave McCleary @ or (203) 306-7819

Custopharm provides a turn-key solution to Foreign Companies interested in selling their generic products in the US

describe the imageCustopharm provides a ''turn-key" solution to Foreign companies interested in selling their products in the US Market, we have supported companies from every continent.  Many companies have interest in expanding markets for their generic products, especially the US market.  

It is not necessary to open a US office, this can cost millions of $ before you have FDA approval on your first generic product. 

Custopharm has a great deal of experience, we have supported more than 50 companies around the world.  (Australia, Bangladesh, Brazil, Canada, China, Croatia, France, Germany, Greece, India, Italy, Poland, Portugul, Spain, Turkey, and others. 

We have assisted our overseas customers by serving as the US Agent, reviewing their documentation prior to manufacturing the stability batch, then submitting the eCTD ESG ANDA and responding to deficiencies. 

Also have a program where we review the documentation that will be used for the qualification batch, perform a gap analysis as to what the FDA regulations require, this helps reduce the number of unnecessary deficiencies. 

Custopharm can also provide the regulatory maintenance function once the product is approved.

Custopharm filed the first eCTD ANDA in 2004, have filed well over 100 since.  We have 9 years of experience with eCTD filings.  Currently filing 2 eCTD ESG ANDA's per month.  We have a staff of 12 qualified individuals assisting with the effort.

Our fees are ‘all inclusive’ until the application is approved by the FDA.  The beauty of the ‘all inclusive’ pricing is that our goal is to get your approval as soon as possible, we are not focused on billable hours.  Our companies share the same goal, both make more money by moving the application through the process quicker.  You will never have to go to your owners/board and tell them there are additional fees/add-ons, a budget you can depend on.

Custopharm provides a reliable service, we have a great deal of interaction with the FDA reviewers during the approval process.  The applications we ‘fully write’ are approved sooner than the ANDA’s we publish, in many cases there is a significant improvement in approval times.  The deficiency responses are all written in a way that is acceptable to the FDA, we filed over 100 deficiency responses in 2010, over 100 deficiency responses in 2011, this provides a valuable benefit to your company.  Minimizing the severity of the first round of deficiencies and reducing the number of review cycles is ‘paramount’ to Custopharm.

ANDA approval times for our customers are significantly quicker than the industry average.

Custopharm can also connect you with US Marketing companies that can distribute your products.

If interested please contact:

Dave McCleary

Custopharm, Inc.


(760) 481-7590  office

(203) 306-7819  cell

eCTD ANDA Submission Statistics


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FY 2009

•859 ANDAs submitted in FY 2009

•263 PIV submissions

409 eCTD submissions

242 CTD submissions

30 paper CTD submissions

178 Gateway submissions

8 ANDA's RTR's (Refuse to Review) in FY 2009


FY 2010

•813 ANDAs submitted in FY 2010

•262 PIV submissions

119 CTD submissions

271 eCTD submissions

12 paper CTD submissions

411 Gateway submissions

13 ANDA's RTR'd in FY 2010


FY 2011

•853 ANDAs submitted (as of 9/26/2011)

•211 PIV submissions

60 CTD submissions

177 eCTD submissions

5 paper CTD submissions

611 Gateway submissions

•48 ANDAs RTR’d (as of 9/26/2011)


Relevance of numbers

100% of Original ANDAs being submitted are in CTD format (eCTD+paper CTD+Gateway)

Approximately 95% (or more) of original submissions are now electronic

Gateway submissions have continued to surge tremendously

58=(2008) 178=(2009) 411=(2010) 611=(2011)

RTR's as a percent of submissions is about 17% (data is incomplete as all of FY 2011 submissions have not been reviewed)  FY 2008=15%, FY 2009=9%, FY 2010=14%

FDA currently has approximately 2500 ANDA's under review

FDA currently has approximately 4900 CMC Supplements under review 

*All information above from GPhA Technical Conference held in Bethesda, MD - Oct 3-5 Kwadwo Awuah, Pharm D., R.Ph,. Regulatory Support Management Officer, Office of Generic Drugs, FDA


Industry average ANDA approval times are approximately 33 months, industry has done an excellent job converting to electronic ANDA filings from paper.

The focus for industry remains to provide the FDA 'well written' ANDA applications, this will assist the FDA with more efficient review times.

Custopharm filed the 1st eCTD ANDA in 2004, have filed over 100 since.  Custopharm assists companies by through Regulatory assistance, when we fully write eCTD ESG ANDA's the average approval time is significantly faster than the industry average.


Dave McCleary

FDA Issues Revised Guidance on Marketed Unapproved Drugs

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On September 19th, 2011 the FDA announced a revision to its 2006 guidance titled “Marketed Unapproved Drugs-- Compliance Policy Guide Sec. 440.100, Marketed New Drugs Without Approved NDAs or ANDAs” (CPG 440.100). This revised guidance clarifies that any unapproved new drug introduced onto the market after September 19, 2011 will be subject to immediate enforcement action, without prior notice and without regard to the enforcement priorities set out in CPG 440.100.

Custopharm can assist with filing ANDA's and NDA's.  We filed the 1st eCTD ANDA in 2004, have filed over 100 ANDA's since, approved for the Electronic Submission Gateway (ESG) in 2008, responded to over 100 deficiencies in 2010.  Custopharm will make you feel comfortable knowing that your submission is of the highest quality. 

Custopharm can also assist with Drug Listings, Establishment Registrations, and SPL filings.


Dave McCleary

Budget reductions & User Fees - ANDA approval times?

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Consider these points:

Compliance has 192 foreign inspections scheduled, resources to complete 62 in 2011.  The number of facilities that require inspections has increased in the last 5 years.  Consider only 6 years ago there were less than 20 Chinese facilities inspected and approved for API, now there are over 200.  A wave of Chinese Dosage facilities have filed ANDA's which will require inspections and additional effort. Numbers in India have also grown with API manufacturers and Dosage facilities over the last 6 years.  The additional overseas work created for the Compliance group is significant.

Most likely Federal funding will be cut back in 2012, talks of up to 10%.

Assuming a reduction in the number of inspections and headcount in 2012, the average ANDA approval time could continue to increase.

The possibility of User Fees for Generic applications can generate additional revenue, but will these fees be channeled directly to CDER or will a portion go to the General Accounting Fund?  Additional dollars could potentially reduce the average ANDA approval times, or these fees could balance out the potential cuts to the budget.

None of us know how this will balance out next year, companies must think of ways to be most effective and efficient in order to manage the change ahead.

A key to success will be the Regulatory strategy, a 'well written' eCTD ESG ANDA will minimize the efforts of the reviewer. 

Don't try to 'save money' with a low cost Regulatory Consultant, now is the time to work with an experienced company that knows what they are doing.  A poorly written, poorly managed ANDA can cost a company in excess of 24 months of review time, not to mention creating an unnecessary burden on the reviewer.

Custopharm filed the first eCTD ANDA in March 2004.  We have filed over 100 eCTD ANDA's, over 500 ESG filings.  We file 'well written' eCTD ESG ANDA's, you can be confident that a quality application has been filed with the reviewer's needs in mind.


Dave McCleary

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'Well written' eCTD Gateway ANDA filings most efficient

Regulatory approval time lines should be a key focus for all Generic companies, even more important than development time lines.  Companies must understand a poorly written application could potentially cost them 12-18 months of time on the market. 

Average ANDA approval times are approaching 34 months, most blame the FDA.  But is this the case?  We don't think so.

The FDA receives applications from a vast array of companies, many from overseas.  Custopharm has reviewed documents from over 35 companies, many of the applications we see are 'data dumps' to the FDA.  Too much information is submitted to the FDA reviewers which clogs up the system and wastes the reviewers time.  Another critical issue is how the ANDA is written, every company has a different style of formatting the application, this also adds time to the review.  Language barriers can create confusion to the reviewer, this adds additional questions to the sponsor of the application.  Last but not least, many applications are not complete which creates additional cycles of review adding to the work load of the FDA reviewer.  

Custopharm can assist with review of the development to assure the ANDA is complete, we can then write a 'well written' application with the FDA reviewer in mind, we also assist with deficiency responses.  Custopharm has filed over 100 eCTD ANDA's and over 500 ESG filings, we filed the 1st eCTD ANDA in March 2004.  We are good at what we do and are fair to our customers.

FDA Generic Drug User Fees

Money QuestionHaving just returned from the DCAT meeting in New York City, all the buzz was about the seemingly imminent "Generic Drug User Fees."  Everyone had questions, opinions, suggestions and speculated about the upcoming fees. The main questions were how big the fees would be (especially from smaller companies with limited resources), the impact the fees would have on ANDA approval times and when they would start.  It seems everyone had a different answer or idea for the various questions. I heard people discuss feels as small as $20,000 per ANDA to upwards of $100,000 per ANDA.  Timelines seemed to range from sometime during the second quarter of 2011 to sometime in 2012.  Nobody had an answer to the impact that the fees would have on approval timelines but consensus seemed to be that a target of 18 month approvals would be ideal.  The only thing that wasn't in question was whether or not the fees would happen.  Everyone agreed that they would happen and most were optimistic to their success.

User fees have been implemented with varying success at the difference divisions at FDA.  CDER has implemented PDUFA fees for NDA submissions with success in sticking to the review times in most instances.  However, if you read the statistics regarding the decreasing number of new drugs being approved, the real question revolves around the cause of the timelines being kept is it due to the number of filings or due to the fees.  Additionally, PDUFA fees for NDA are very large and have created a secondary issue.  The FDA would love to remove all unapproved "Grandfathered" products from the market, however the large PDUFA fees make it cost prohibitive to submit an NDA for these products. 

On the other side of the coin, CVM has issued reasonably sized filing fees for veterinary drug products but has placed the money in the general reserve fund (or at least so I have been told) and therefore approval times have not improved since implementing the fees.  From what I hear,  CVM makes OGD look good with the 30 month ANDA approval times.

One other question that poses itself is how do you address, the more than 2,000 ANDA that are currently backlogged once the fees start.  Do they keep their place in line or do the get bumped for "priority" paid submissions.A definite concern on industry is if the fees are used to supplement or replace the current Federal Government's funding for OGD.  If it replaces, I do not think things will get better quickly if ever.  If it supplements the fees, then I think eventually we will get to a much better system wherein timely approvals are possible and to be expected.

In conclusion, it seems not matter what the FDA does, the problem will not be solved overnight.  And if you read my previous blog; in Custopharm's opinion one of the primary reason for much of this backlog is poorly written applications that recirculate through the FDA over and over again.

We welcome any comments, thoughts, opinions and theories you may have on this subject matter.  Please feel free to comment in the space below.

Improving ANDA Approval Times: Part 1 FIFO

gantt chartAs the title illustrates this article will apply mainly to ANDA approval times since currently there are no PDUFA or User Fees for generic drug products.  Even when and if the user fees reach generics there is no assurance that they will work the same way as they do for NDAs with action dates that are essentially adhered to.

During product development and submission preparation. everyone is familiar in at least some regard with the use of Gantt charts as a project management tool.  Gantt charts are a great tool to track and plan in-house or contracted activities for which the sponsor has at least some direct control.  Additionally, most Gantt charts I have seen go on to predict expected dates for FDA application acceptance, deficiencies and approval times.  However  these times were essentially based on empirical evidence or examples that is outdated due to ever changing conditions at the FDA.

We have divided the FDA review process into four main areas; FIFO cue time, review time, deficiency response time and approval time.  Everyone's target is to get to the approval time as quickly as possible, however to get there it is essential to manage the three other phases as effectively as possible.  Today I will address the FIFO Cue time.

The FDA operates most applications in a First In First Out procedure or FIFO. There are some exceptions such as expedited application or products on the drug shortage list.  However, those are out of the scope of this discussion.  Our definition of FIFO cue time is the time your submission sits around waiting for it to be picked up for review.  

There are not many things that an individual can do to improve the FIFO cue time for a filing since, it is a general issue that effects all companies.  The only things that you as an individual company can do to improve your cue time is to get your submission in the cue as quickly as possible.  This means filing the submission earlier and ensuring that your company is using the Electronic Submission Gateway (ESG) to submit your filings.  

Beyond these two things, the only ways to improve FIFO cue time is to have fewer submissions enter the FDA (which we all know isn't going to happen) or for the industry as a whole to submit higher quality filings that actually have a single cycle approval process.  The key contributor for long FIFO cue times are applications that are essentially stuck in the system.  By this I mean filings that have received multiple rounds of similar deficiencies and are not prepared in a manner that is easy to review.  Typically these submissions are filed by companies that are not familiar with FDA processes or do not place emphasis on regulatory.

To improve this the industry needs to start looking at the regulatory function as an integral part of the product development process.  Submitting an application to the FDA is much more than just following guidance documents and providing the data to the FDA.  THe process is based on experience from previous applications, working with reviewers, and providing the information to the FDA in a logical easy to follow pattern.  Keep in mind that each additional deficiency cycle add months to your product launch date.

ANDA Review Times

There is a growing application backlog and median time for ANDA approval by FDA’s Office of Generic Drugs (“OGD”).  The median ANDA approval time in Fiscal Year 2009 was 26.70 months.  This is up from 21.65 months in Fiscal Year 2008 and up from 17.3 months in Fiscal Year 2003.  Today, the ANDA backlog has surpassed the 2,000 application mark and is reportedly growing at about 100 applications per month. We understand that the median ANDA approval time is edging closer to 

30 months from application submission.

Companies must submit ‘well written’ regulatory filings.  There is so much effort in compressing development timelines, it is critical to file the most efficient ANDA/NDA/IND possible to compress review times.

If you are

 not filing ‘well written’ regulatory filings it is costing your company time and money.  We have countless examples of how the ‘well written’ Gateway filing improves approval timelines.  

The above statistics are the building blocks to file a superior filing to the FDA, we continually implement what we learn to build a stronger A

NDA/NDA/IND.  When Custopharm fully develops a product there are fewer review cycles with the FDA, each review cycle can cost months of ‘on the market’ time.  Custopharm understands the technical aspect of development.

-Custopharm has filed many IND’s for development companies.

-Custopharm filed the first eCTD ANDA in 2004


 has filed over 90 eCTD ANDA’s

-Custopharm w

as approved for the Electronic Submission Gateway in May 2008, filed over 475 since.

-Custopharm has filed 159 Gateway filings in 2009

-Filed 100+ Gateway filings through May 15th, 2010

-In 2009 Custopharm responded to over 100 deficiencies

Trust your Regulatory filings to Custopharm, a 'well written' ANDA has become more important

 than an efficient development timeline.  More time on the market means more profit in your bottom line. 


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