Catawba Research Concludes Another Rosacea Clinical Trial

Rosacea Clinical Trial Spotlight:

Catawba Research is pleased to announce another achievement for a recently completed rosacea clinical trial. In this trial, Catawba enrolled more than 1000 rosacea subjects in 22 weeks from 33 sites.

The time line for the entire project including investigational product at the site to delivery of final clinical study report was 9 months.  Catawba Research continues its excellent 100% track record in successfully completing clinical trials on time without a single change order.

Catawba Research is proud of yet another rapid study completion and committed to achieving aggressive timelines for our clients.

See more about this program in the enclosed press release:

Rosacea Press Release

Learn more about our rosacea CRO services or get in touch with us for additional information.

Acne First-to-File:

The team at Catawba Research has recently completed a first-to-file submission for acne clinical trial . In this study, Catawba enrolled a staggering 1125 acne vulgaris subjects in 8 weeks from 12 sites.

The time line for the entire project from the delivery of investigational product at the site to submission of final clinical study report was 6 months. Catawba Research has a lot to be proud of: our sterling record of successful completions of Phase III clinical trials coupled with our innovative approach to clinical research, has further enhanced our reputation in the industry.

Catawba Research is proud of this first-to-file milestone and committed to delivering quality results within fast timelines for our clients.

See more about this program in the enclosed press release:

Acne Press Release

Learn more about our acne CRO services or get in touch with us for additional information.

Route 505(b)(2) vs. 505(j)

Your life is consumed by the single minded challenge of developing a generic drug product by navigating the FDA’s 505(j) regulatory pathway. Your journey has finally come to an end. The FDA has issued you an approval. Congratulations! You’ve endured this journey at a great financial risk; testing your business and scientific acumen. Not to mention the legal battles that could have taken you to the ‘poor house’ and ‘nut house’.

However, you have arrived at an already over-crowded souk with competitors from the 4 corners of the globe, selling their wares. Your approval is rapidly declining in worth due to the existence of other AB rated ANDAs (Abbreviated New Drug Application) and most likely, there are more to follow on the next caravan of approvals.

Upon reflection, investing your money in a Dunkin Donuts franchise or a nail salon may have a wiser decision, but pharma is all you know. May be another regulatory route with a quicker approval time and the potential for a greater reward may have been the more appropriate route to pursue. You’re too poor for a full on New Molecular Entity (NME) New Drug Application (NDA) and you’re still licking your wounds from your ANDA battles. Where do you go from here?

“Difficult situations inspire ingenious solutions”, Plato (maybe)

Won't you get hip to this kindly tip, and go take that regulatory trip, get your kicks on Route 505(b)(2). What is that?


505j pathwayTaking the 505(b)(2) route may have led to a quicker market approval of your new product and ensured that you are the only one at the finish line, likely to be alone free to sell your product unopposed for 3 to 7 years.

This paper will outline offer a historic overview of the regulatory landscape and will compare and contrast the 505(j) and 505(b)(2) regulatory pathways, with examples of successful ‘transformations’ of generic products into ‘branded generics’ and their impact on the consumer.

With a greater threat from the generic pharmaceutical industry, coupled with lengthy and costly development programs and a limited product pipeline, pharmaceutical companies of innovator drug products have looked to creative regulatory ways to maintain their competitive edge.

Section 505 of the Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments) describes three types of new drug applications:

  1. 505(b)(1). The traditional NDA route with full reports of investigations of safety and effectiveness
  1. 505(b)(2). An NDA with full reports of investigations of safety and effectiveness but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference.
  1. 505(j). ANDA used for generic drug approval.

The 505(b)(2) application was intended to motivate innovation without creating duplicate work on what is already known about a drug. Therefore, it is possible to submit a 505(b)(2) application that relies on literature and data not developed by the applicant i.e. the FDA’s finding of safety and effectiveness for a previously approved drug product (e.g., to support a new claim). As outlined in Figure 3 (below), there has been a steady increase in 505(b)(2) applications and subsequent approvals.

“Does this qualify for a 505(b)(2)?”

A 505(b)(2) application can be submitted for products that are either a New Chemical Entity (NCE)/New Molecular Entity (NME) or for those previously approved with new changes. In either case, an application may rely on the Agency's finding of safety and effectiveness of the previously approved product, coupled with the information needed to support the change from the approved product, i.e. bridging studies or published literature. In October 1999 by the FDA published the Guidance for Industry, Applications Covered by Section 505(b)(2), in which the agency identified the types of applications that are covered by section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (the Act). Below are examples of 505(b)(2) applications:

  1. New Molecular Entity (NME)
  2. Change in dosage form
  3. Change in route of administration
  4. Substitution of an active ingredient in a combination product
  5. Formulation changedrug exclusivity
  6. Change in active ingredient
  7. Dosing regimen
  8. Combination product
  9. Bioinequivalence
  10. Change in strength
  11. Unapproved drug products (DESI); see below

The 505(b)(2) regulatory pathway has been widely used by a variety of small, medium as well as large pharmaceutical companies for an array of examples as listed above.

Figure 3: Continued growth in 505(b)(2) approvals. The 505(b)(2) route continues to be a viable opportunity for many pharmaceutical companies.

505(b)(2) NDAs


The Drug Efficacy Study Implementation (DESI). ‘Youthful old drug’

hip manThe Drug Efficacy Study Implementation (DESI) was the process used by FDA to evaluate for effectiveness for their labeled indications over 3,400 products that were approved only for safety between 1938 and 1962.

The FDA estimates that in the United States until recently perhaps as many as several thousand drug products are marketed illegally without required FDA approval. As a result, the agency has undertaken a vigorous exercise to enforce the Federal Food, Drug, and Cosmetic Act (1962) with regard to drugs marketed in the United States that do not have required FDA approval for marketing.

A DESI product can be ‘legitimized’ and brought to its youthful state by a company submitting and gaining approval via the 505(b)(2) pathway. Once approved, the FDA normally intends to allow a grace period of roughly 1 year from the date of approval of the product before it will initiate enforcement action (e.g., seizure or injunction) against marketed unapproved products (older products) of the same type, it is possible that a substantially shorter grace period would be provided, depending on the individual facts and circumstances.

Financial advantages of this ‘pharmaceutical plastic surgery?’

The advantage to companies pursuing the policy of gaining approval for their DESI product has resulted in extremely favorable market conditions for the sponsors, as best illustrated by colchicine. URL Pharma used publications and commissioned studies to show that colchicine was safe and effective, and received patents on its formulation. URL Pharma also sued five makers of manufacturers of colchicine, claiming they have been illegally marketing their colchicine products since Colcrys’s approval (URL Pharma’s brand name). URL Pharma has claimed that its approval helped make colchicine safer for everyone, noting there wasn’t even a standard dosage for the medicine until the company went through the FDA approval process.   URL was sold for a substantial profit; Colchrys is now owned by AR Holding Company and Takeda Pharmaceuticals USA.

Let Catawba Research, LLC be your guide

Catawba Research, LLC is currently involved in a number of 505 (b)(2) clinical programs. Our clients have realized the cost and time advantages of pursuing this regulatory route and have chosen Catawba as their guide on their journey.

Successful ‘transformations’ of generic products into ‘branded generics’ via the versatile 505(b)(2) regulatory pathway has offered a time and cost effective solution to our clients to become ‘innovative’ and offer solutions to the consumer by providing improved and modified versions of previously approved products that benefit the patient.

We are looking forward to taking you on this exciting journey. For more information, explore our website.

The quest for consistency in subjective clinical assessments, has led to the development of a number of grading methods to achieve data reliability. Whether it is the IGA, PASI, PGA or signs and symptoms scale to assess severity, the inherent nature of the subjective assessments still plays a role in impacting good reproducible and robust data.

At Catawba Research, we are acutely aware of these challenges, and as such, we are working with industry leaders to develop tools to provide us with consistency and reproducible data. Ultimately, excellent data is what our clients and the regulatory agencies strive to achieve.

Here at Catawba Research, one of the things we get most excited about is continually improving processes and finding new ways to approach clinical research. We like to think outside the box and develop new methods to improve the overall quality and outcome of our clients’ clinical trials.

We are pleased to announce the arrival of our latest brainchild – training videos! We have been hard at work developing and filming a series of comprehensive, indication and product-specific training videos for the individual therapeutic areas we're conducting trials in. Each video is extensive, with more than 30 minutes of technical information specific to that indication or product, as explained by a key opinion leader in the industry. Following the deep dive into the indication or product, trainees will get to take part in a brief test to aid in retention of the topic.

These videos are intended for the key study team members involved in the clinical trial. This initiative is part of a comprehensive approach to training, as CRAs and investigator sites will receive this training on top of their standard therapeutic and protocol training. The overall goal of these video lessons is to improve consistency, reduce variably, and yield more robust data. We are confident this innovative approach to training is something that will greatly benefit all parties involved and improve the outcome of our clients’ programs.

Catawba Research is committed to being a pioneer in our therapeutic areas of focus, which include dermatology, women's health, and ophthalmic clinical trials. These new, state of the art training videos are the result of months of hard work, and we couldn't be more pleased with the end product. We look forward to future iterations and continuing to find new ways to add value to your clinical programs.

To learn more about our training program or see some our videos, contact us!

An Overview of GDUFA

Introduction to The Office of Generic Drugs (OGD)

The Office of Generic Drugs (OGD) reports directly to the Director of the Center for Drug Evaluation and Research (CDER). The OGD’s mission is to ensure safe, effective, and affordable medicines for the American public.

The OGD helps ensure that human generic drug products are thoroughly tested and shown to meet the statutory standards for approval. The OGD’s work has helped millions of Americans to use quality and affordable generic drug products to treat a wide variety of medical conditions and in turn save the American health care system over $1.6 trillion over the 10-year period from 2005 through 2014. Under the Drug Price Competition and Patent Term Restoration Act of 1984, or Hatch Waxman Act, recent evidence has shown that the OGD has helped save Americans over $254 billion in just in 2014 alone.

This Success Brought New Challenges

Over the last several decades, the generic industry, the number of generic drug applications (known as “Abbreviated New Drug Applications” or “ANDAs”) submitted to FDA for review, and the number of foreign facilities making generic drugs grew substantially.  As a result, FDA’s generic drug program became increasingly under-resourced.  Its staffing did not keep pace with the growth of the industry.

ANDA submissions

Because the program could not keep up with its workload, a backlog of submitted ANDAs developed and grew. It overwhelmed the FDA staff and created unpredictability and delay for industry.

Pending ANDAs

Solution? GDUFA

What is GDUFA?

The Generic Drug User Fee Amendments (GDUFA) is a recent law passed by Congress as part of the Food and Drug Safety and Innovation Act of 2012. The FDA and generic drug industry developed the proposal for GDUFA. Under GDUFA, industry agreed to pay approximately $300 million in fees each year of the 5-year program.  In return, the FDA committed to performance goals. There are a multitude of metrics that apply to GDUFA, and ultimately the end goal is faster window of review for all Abbreviated New Drug Applications (ANDAs). These metrics and commitments have been ramping up over the course of the first 4 years of the program, as illustrated below.

goals of GDUFA

Because of the amount of hiring, restructuring, and catch-up needed, performance goals were set to commence in the later years of the program.  The GDUFA performance goals with respect to ANDAs, amendments to ANDAs, and prior approval supplements (PAS) are timeframes by which FDA is to take a “first action” on an application, by either granting an approval or tentative approval, or, if there are deficiencies that prevent approval, identifying those deficiencies to the applicant in a complete response letter or in a refusal to receive4 the application.  When deficiencies are identified, industry usually responds by correcting them and resubmitting the application.

Actions on Pre-GDUFA (“Backlog”) Applications

A major commitment of GDUFA was to take a “first action” on 90% of the “backlog” applications, defined as pre-GDUFA applications pending before the Agency on October 1, 2012, by the end of Fiscal Year 2017. As of October 1, 2012, the backlog included 2866 ANDAs and 1873 PASs. The chart above shows that to date, the FDA has completed first actions on 84% of ANDAs and 88% of PASs. And so, FDA is well ahead of schedule in achieving the GDUFA goal to significantly reduce the backlog, and our ultimate goal of eliminating it.

Some of these backlog applications had been pending or in review for a long time prior to GDUFA. At this point in time, as FDA acts on one of the outstanding backlog applications, the “time to approval” of such application will be recorded as, at minimum, 40 months (i.e., we now are three years and four months (40 months) into GDUFA implementation). This helps to explain the often-quoted 42-month approval time, which does not apply to post-GDUFA applications as explained below.

Moreover, the filing backlog for ANDAs has been eliminated. “Filing” is where we evaluate if a drug sponsor’s submitted application is sufficiently complete to permit FDA’s substantive review. In August 2014, we had a filing backlog of over 1,100 applications. Now that backlog is gone. (See chart below).

ANA submission backlog

GDUFA also established goals for our review of PASs. PASs are important because they enable flexibility and improvements for generic drug manufacturing. To date, we have substantially exceeded GDUFA PAS goal of 60% reviewed within 6 months if an inspection is not required and 10 months if an inspection is required.

 PAS review goals

What are the Outcomes of GDUFA?

2016 marks the 4-year mark of GDUFA being instated, and there has already been considerable progress. To support the growth of GDUFA, the OGD hired roughly 125 new employees in 2015. Additionally, employees were hired across the CDER and FDA to help support the GDUFA program, including employees in the Office of Bioequivalence (OB), Office of Research and Standards (ORS), Office of Regulatory Operations (ORO), and Office of Generic Drug Policy (OGDP).

staffing for GDUFA

One of the main goals of GDUFA at the outset was to take “first action” on 90% of applications in backlog (applications submitted prior to the 2012 rollout of GDUFA). The FDA is ahead of schedule in reducing this backlog of several thousand ANDAs and PASs, and by the end of 2015, 84% of ANDAs and 88% of PASs had first actions completed. (See above “Actions on Pre-GDUFA (“Backlog”) Applications”).

A second major focus area has been working through controlled correspondences, which are product development questions that can help companies develop more thoughtful applications. At the end of 2015, the OGD had completed 2,065 controlled correspondences, a record number. (See chart below).

controlled correspondences

Additionally, another strategic focus of the OGD to achieve GDUFA goals has been improving business processes. There have been several notable improvements thus far, including a new informatics platform, improved review processes, and staff training / professional development.

Another outcome of GDUFA has been the issuance of more tangible guidances and standards. The OGD now has product specific guidance documents (also known as bioequivalence or BE guidances) which serve as recommendations to help facilitate pre-market development and efficient filing of generic drugs. The recommendations include useful information on scientifically and clinical supported methods to go about developing a therapeutically equivalent generic version of the branded / reference listed drug. These BE guidances help clarify the expectations of the OGD for specific products, in hopes of supporting the industry in developing generic alternatives to branded drugs more expeditiously.

As of 2015, there are now more than 1,3000 product specific guidances available to the industry, including the introduction of more nuanced products including complex dosage forms. In addition to issuing BE standards, the OGD publishes regulatory guidances focused on the development and approval process. (See chart below).

ANDA BE guidances

An additional goal of the OGD has been more timely and effective communication with the industry. This is being accomplished through an increasing number of forums and webinars.

Finally, as part of GDUFA, the FDA is working with the industry, academics, and the public to develop a list of regulatory science initiatives to further advance generic drug research. This research can provide “new tools to for FDA to evaluate generic drug equivalence and for industry to efficiently develop new generic products in all product categories.” These priority areas for regulatory science research include:

Generic Drug Approvals on the Rise

2015 has been a record year of generic drug approvals, with the OGD awarding more than 580 approvals and tentative approvals, including 99 in December alone. There is much optimism that this trend will continue in 2016 and future years, all towards the larger goal of bringing safe, effective, and affordable drugs to people as quickly as possible. This is certainly an exciting time to be in the rapid-paced world of generics, with many changes and advancements still on the horizon.

Catawba Research, LLC

Catawba Research, LLC is a full-service contract research organization (CRO) providing clinical management services to pharmaceutical, device, formulation development and biotechnology companies. We focus on what we know best: dermatology, women’s health and ophthalmology.

Catawba Research, LLC is your trusted partner for generic drug development, and is proud to have been a part of dozens of successful ANDA applications including a number of “First-To-File” programs.

Have a question about an upcoming project of yours? Reach out to us – we’re happy to help.



Of all the big decisions to be made when conducting a clinical trial, perhaps the biggest of them all is selecting the right CRO for the job. With all the moving parts inherent in a trial, it is critical to find the right partner, and one that can deliver results in a timely and cost-effective manner. But what criteria should a sponsor look at when selecting a CRO? Here we outline some of the major factors you should weigh when making this decision.

Cost – Perhaps this is an obvious statement, but naturally cost will be a determining factor for most sponsors looking to run a clinical trial. It is important to select a partner that can perform your trial within budget. Unfortunately, regardless of how much you like a CRO, if the cost is too high it can be a deal-breaker. This is a delicate balancing act however, because while it may be tempting to go with the lowest bid for the project, you need to stop and consider and a few things:

One other approach to manage cost in clinical trials is through getting the CRO to bid based on your template, i.e. 'bid grid'.

Depending on whether you prefer a fixed fee type of arrangement or a pass-through arrangement, you have many options when finalizing cost with your CRO.

Finally, one other solution to help keep trial costs under control is through a discount for a group of trials. Perhaps you have a group or series of trials on the table. If you feel confident you have found the right CRO to partner with, you can often get a discount across the board for awarding the package of trials to that CRO.

Timelines – We all know meeting timelines is of paramount importance to the success of a critical trial. Every CRO is going to promise that they will deliver on your aggressive timelines. But how can you be sure this is true? When evaluating CROs for their ability to deliver on-time results, look for a prior track record of proven success in meeting milestones. Your partner should be one that has consistently performed on time or ahead of schedule.

Another way you can help ensure the CRO you are partnering with will meet timelines is to have certain assurances and even incentives built into the contract. There can be a monetary bonus at stake to help motivate the CRO to deliver results ahead of time. On the flip side of the coin, if milestones are missed, it could lead to a penalty to be paid back to the sponsor. Thus, by clearly setting expectations ahead of time, both parties will be held accountable to delivering on those milestones.

Quality – It may go without saying, but quality of the data is critical to the overall success of the clinical trial. But how can a sponsor be sure that their CRO will deliver quality data? It is important to look into a proven track record of success. If the CRO you're considering has a history of delivering successful results, this is usually a promising sign. Additionally, you can conduct a quality audit of your prospective partner. Do they have any past 483's? Are there any red flags that you uncover? It is important to do your due diligence before entering into a partnership.

Finally, the therapeutic experience of a CRO can profoundly impact the quality of the program. If the CRO and its project personal have worked on that indication before, that expertise will benefit the overall execution and quality of the trial.

Communication – Moving beyond the more obvious criteria, communication is a very important factor when selecting the right CRO. While larger CROs offer benefit in their vast experience, the potential downside is infrequent communication. Project managers at larger CROs are often managing many huge studies and don't have the time to provide frequent communication to all their sponsors. On the opposite end of the spectrum, smaller CROs will likely provide you with a project manager who is very dedicated and committed to your project. In addition to frequency of communication, the style of communication is another important consideration. When evaluating CROs, make sure you know which project team members will be running your project and that you feel comfortable working with those individuals. There are always going to be some roadblocks that arise during the course of the trial, but as long as you feel you have a partner you can communicate with effectively, then those hurdles can be overcome.

Strategic Thinking – Finally, when choosing your CRO, don't underestimate the power of a partner who can think strategically. While it is easy to send out the specs of a project and receive a series of bids in return, not all projects are straightforward. Depending on the indication or type of clinical trial at stake, there are more often than not many intricacies that need to be taken into account. The good CROs will separate themselves from the pack by recognizing those nuances and offering suggestions or creative ideas to potentially approach the trial in a different manner. From their experience in this therapeutic area, they may know a way to improve oversight, mitigate risks, or design the trial differently to factor in important variables. Ultimately a discussion can take place and both parties can decide the best way to run the trial, but a CRO that demonstrates the ability to think outside the box is a valuable partner.

Catawba Research, LLC is your perfect CRO partner:

By using these five criteria, you can hopefully sift through the list of prospective partners and choose the right CRO for your upcoming clinical program. Catawba Research lives by these five pillars and is dedicated to providing excellence to our sponsors. To learn more about Catawba Research's services or to request a quote on an upcoming project, reach out to us.

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