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
$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.
According to the FDA's 2013 generic drug user fee:
ANDA's submitted on or after October 1, 2012 must pay $51,520
ANDA's submitted prior to October 1, 2012 not yet approved must pay a backlog fee of $17,434
Prior approval supplement (PAS) submitted on or after October 1, 2012 must pay $25,760.
DMF's submitted on or after October 1, 2012 must pay $14,940.
Fees are due on the date of submission.
If an ANDA or PAS was submitted before October 1, 2012 the fees are due on November 24.
**All companies must Self Identify, this will allow the FDA to track fees. Custopharm can assist companies with filing their Self Identifier electronic filing.
Any questions please contact Dave McCleary @ 203 306-7819 or email@example.com
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 @ firstname.lastname@example.org or (203) 306-7819
The Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law on July 9, 2012, and effective on October 1st, 2012, amends the Act by requiring additional information to be submitted for the registration of domestic or foreign drug facilities. This additional information includes the unique facility identifier of each drug establishment and a point of contact e-mail address. Furthermore, as of October 1, 2012, the re-registration period for domestic and foreign drug manufacturers has been changed to October 1st to December 31st of each year, instead of the previously more open-ended period of on or before December 31st of each year.
Custopharm can assist our customers with this service.
For assistance please call Dave McCleary @ 760 481-7590 or by email email@example.com
Custopharm 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:
(760) 481-7590 office
(203) 306-7819 cell
Aspire LLC announces the release of Aspire eCTD software
Aspire LLC has released revolutionary submission software - Aspire eCTD.
Round Rock, Tx., July 20, 2012 - Custopharm, a leading company who specializes in electronic submissions and McSnyder Software have come together to develop Aspire eCTD - a revolutionary submission software product that offers a user friendly experience to successfully construct and submit eCTD filings.
Aspire eCTD introduces an all in one submission software that was designed from the ground up to make electronic filings easy and successful. Some of the submission software currently on the market is tedious and complicated. For this reason Aspire focused on the user interface of Aspire eCTD to make it simple yet still powerful and comprehensive. Aspire eCTD has many complex document management features, as required by the FDA, yet still allows its users to navigate through the software with relative ease.
“Aspire eCTD will revolutionize the way companies submit electronic eCTD’s,” says Fred Defesche, Partner of Aspire LLC. “We have created the software with the user in mind. We know how complicated eCTD submissions are and we used that knowledge to build a product that harnesses the complexity of the FDA approval process with a user friendly design.”
The Aspire eCTD software release delivers many unique features:
- Absolutely NO need to learn XML!
- A Visual submission history with a graphic view of how a document changes over its lifetime
- A built in validator that alerts users to potential issues by the FDA and other regional submission authorities. Unique to the market, many issues can automatically be corrected by Aspire eCTD within the document saving a significant amount of time
- Included validator that redirects error messages to the exact location of the error in the documents for correction
- Allows users to import submissions that have been created from other software
- Multi-user shared repositories and working on the road(offline) capabilities
- Outperforms other existing eCTD software by delivering submissions quickly and easily
Aspire eCTD software is supported by the regulatory expertise of Custopharm, who has filed over 150 regulatory submissions with Aspire software during the past year. Custopharm has 9 years of eCTD experience, filed the first eCTD ANDA in 2004, and submitted well over 100 since, has also filed many IND’s & DMF’s.
About Aspire LLC
Aspire LLC., founded is headquartered in Round Rock, TX, is a products and services company providing best of class tools needed to take Pharmaceutical Companies drug products through the electronic drug approval process. For more information, please visit http://www.aspireectd.com.
European Medicines Agency and United States Food and Drug Administration to share manufacturing site inspections
|The European Medicines Agency and the United States Food and Drug Administration (FDA) are launching an initiative to share work on inspections of manufacturing sites in each other's territories. The initiative, starting in January 2012, will enable the two authorities to rely on each other's inspection outcomes rather than carrying out separate inspections in duplicate. This is expected to:
- enable better use of the two authorities' inspection resources;
- reduce the burden of inspections for medicines manufacturers;
- shift the authorities' inspection capacity to other regions.
The initiative will apply to inspections of manufacturing sites of human or veterinary medicines in the European Economic Area or United States of America. It will focus on sites that are already known to the two authorities and have a history of compliance with good manufacturing practice (GMP) following previous inspections.
This is the latest step in increased collaboration between European authorities and the FDA. In August this year, the authorities announced the successful completion of two pilot projects involving the sharing of information on inspections.
The outcomes of the initiative will be reviewed after three years.
*Article written by PharmaNews on 12/12/11
Interesting article from the WSJ - 11/2/11 This IS the solution - allow companies to make money on products in demand.
The Bush-Obama Rx Shortages
Critical cancer drugs are in short supply thanks to price controls.
This week President Obama finally confronted a major U.S. health-care disgrace—the growing shortages of lifesaving drugs, especially anticancer therapies. For some reason the White House lumped its executive order with its "we can't wait" campaign against House Republicans, but the pity is that we will have to wait, because the only genuine fix is a liberal anathema: market prices.
Shortages have more than tripled since 2005, according to the University of Utah's Drug Information Service, and by the end of the year more than 300 products are likely to be back-ordered, in short supply or totally unavailable. Some are anesthetics and pain therapies, others emergency room "crash cart" drugs. But most—about 70% in 2010—belong to the class of drugs known as "sterile injectables" that are mainstays of the chemotherapy arsenal, such as paclitaxel or cytarabine.
The result is that more and more patients are receiving substandard care—relying on less effective or more expensive substitutes or else forced to postpone treatment. In oncology, delays of weeks or even days can be fatal.
Most sterile injectables have been off-patent for decades, but unlike other cheap generic drugs with low profit margins, production is complex and requires special facilities. Nonetheless, George W. Bush and the Republican majority decided that Medicare was "overpaying" for these cancer drugs and included a 6% cap on price increases every six months in the 2003 prescription drug bill. These new price controls (which apply to the providers that purchase the drugs) took effect in 2005, when the shortages began.
In a rational market, sterile injectable prices would now be rising to encourage more supply, since the demand for cancer drugs is inelastic. The old reimbursement system, called "buy and bill," was imperfect, but at least it allowed prices to float and wasn't producing the scarcity that central planning always does. The sterile injectables that are in short supply currently sell for $37.88 a dose on average, and modest price increases could make the market economic.
The problem is compounded because Food and Drug Administration rules cause pointless delays. It takes as long as two and a half years to receive FDA manufacturing approval for a generic, so other drug makers can't ramp up production if a company cancels a product line due to these disincentives or even if the fragile supply chain for sterile injectables is contaminated and manufacture is delayed.
Mr. Obama's executive order will do little if any good since it doesn't address or even mention this underlying distortion that Medicare has created. Instead, it merely expands the FDA reporting requirements about production interruptions or terminations. This is supposed to be an early warning system, but the scandal is that the availability of basic medicines could be allowed to become an emergency.
The order also tells the Justice Department to crack down on the "grey markets" that have sprung up to deliver supplies to doctors and hospitals, albeit with the inevitable markups. So rather than allow price signals to govern supply and demand, Mr. Obama wants to suppress them further.
The larger danger apart from the risks to the patients forced to receive compromised treatment is to the future of cancer progress. The common chemotherapy drugs are critical in clinical trials as the standard regimen or in combination with new options, and the Coalition of Cancer Cooperative Groups reports that as many as half of all ongoing trials require the drugs that are vanishing. This is a delay that really is killing people.
WSJ - November 2nd, 2011
•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
•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
•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.
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.