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Custopharm Accomplishments - FDA June 20th Deadline


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June 20th Filing Deadline Accomplishments


Custopharm, Inc. is proud to announce that after a very busy two months our regulatory group submitted 38 ANDAs before the June 20th cutoff.  This does not include the numerous amendments, supplements, annual reports, drug listings, labeler codes, self-identifications and establishment registration filings.  This was accomplished with a team of 10 dedicated employees.

We are extremely thankful and proud of the entire regulatory team, how they worked together to accomplish what seemed to be an impossible task.  This accomplishment would not have been possible without each employee stepping up and performing to their maximum capabilities.  During the entire process Custopharm didn’t miss any deadline for any customer and everything was submitted on time as has come to be expected of Custopharm. 

To fully describe the significance of the team’s accomplishment, we determined there were at least 600 filings between April and June and Custopharm did 38 of them.  If you take out the larger companies, we predict we submitted between 15% and 20% of all of the generic ANDAs.

Using the Aspire eCTD software was a major help in accomplishing this goal, Aspire is simple to use and affordable.  Aspire allows you to build hyperlinks and bookmarking into the documents prior to validating and publishing, this feature helped us achieve our goals.

We want to thank our customers for putting their trust in Custopharm.




Dave McCleary


Custopharm, Inc.

Delay ANDA Past June 19, 2014 to Save Money?

Money SavingAt first glance it seems obvious, submit your ANDA(s) before June 20, 2014, when the FDA increases the stability requirement from one batch to three batches to save money.  However, there are other things to consider.  This scenario is similar to what happened in September 2012 right before GDUFA started.

In September 2012, everyone rushed to get their submission filed before the full ANDA fee (approximately $51,000 at that time) came into effect by submitting their application before October 1, 2012.  This way a company only had to pay the backlog fee (approximately $17,000).  This essentially saved companies about $35,000.  However, in looking back what is the true cost of this action.  Yes, the filing fee was less but in looking at the GDUFA legislation.  It states 90% of the backlog applications will be acted on by the end of FY2017.  Think about this for a moment, the FDA operates with a First In First Out approach.  Which means those applications submitted in September 2012 are at the tail end of the backlog applications and should hear back sometime in 2017 or later.  This is much longer than typical approval times and will cost years on the market. All in the name of saving $35,000.

Jumping to today, industry is repeating this same short sighted savings.  Let's summarize what we know.

  • FDA will require 3 batches and six month stability.

  • GDUFA time lines come into effect for the first time October 1, 2014 which a target date of 15 months.

  • All submissions (excluding priority or Paragraph IV submissions) have no required time lines for review.

  • The FDA has heavily advertised how they have  met or exceeded all GDUFA requirements.

  • There will be essentially zero ANDA filings between June 20, 2014 and October 1, 2015.

In looking at the aforementioned facts,  we can easily see that there will be extra costs in the manufacture of the three batches and time lost in the acquisition of the extra three months of stability data.  The extra costs translates comes from extra API cost, manufacturing costs and stability costs.  However, in many cases there is some reduction in costs due to the use of bracketing and matrixing which can be employed with the three batch approach.  That being said there is an extra cost which is substantial.

All applications currently filed have no review time frame associated with them, we have seen variability in receiving responses between 20-30 months from the time of filing.  Obviously, there are many factors that cause this variation and many products are outside of this variation both longer and shorter. In any event, it much longer than the 15 months promised by the FDA starting October 1, 2014.  Additionally, with essentially no submissions being submitted between June and October, the FDA will be able to get organized for the new submissions that will have target dates associated with them.  Based on this, you lose three to four months waiting for the stability data but gain on average 9-12 months in review time.  Doing simple math, the time savings are about half a year (6 months).

This obviously assumes that the FDA will achieve their time frames but based on the most recent FDA presentations they will do what they can and considering it is the first time target dates are in effect. I am sure at least initially they will.  Other target dates, related to amendments will affect both submission types equally.

The final consideration is the status of your facility. If you have a facility that is filing a generic application for the first time, then there are establishment fee savings.  The FDA has stated that facility fees are due whenever a facility for the first time has a referencing application active, submitted or pending on the due date.  This means, if you submit in October 2, 2014 then your first establishment fee is due October 1, 2015.  This with the shortened review time will result in the removal of one or two establishment fees prior to you approval.  Currently the establishment fee is about $220,000 for domestic facilities and $235,000 for foreign facilities.  This fee is an annual fee subject to change yearly.  For facilities filing an ANDA for the first time the savings are significant.

In conclusion, there are several factors that define a companies path forward with respect to the timing of the filings. Many companies as pressing very hard to meet the June 19, 2014 filing time frame with the goal of saving money and time.  Companies should evaluate the big picture to determine what is best long term as opposed to just looking at today.  If you are pressing too hard complete a filing, the odds of having mistakes in that submission and therefore receiving a Refuse to Receive increase drastically.  This has enormous consequences in lost fees, API costs, manufacturing costs, testing costs and most importantly time.

For assistance contact, Fred Defesche via email at or via phone at 760-481-7811.

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.

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