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?
Taking 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:
- 505(b)(1). The traditional NDA route with full reports of investigations of safety and effectiveness
- 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.
- 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:
- New Molecular Entity (NME)
- Change in dosage form
- Change in route of administration
- Substitution of an active ingredient in a combination product
- Formulation change
- Change in active ingredient
- Dosing regimen
- Combination product
- Change in strength
- 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.
The Drug Efficacy Study Implementation (DESI). ‘Youthful old drug’
The 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.