NDA Submissions: 505(b)(1) & 505(b)(2)


Because the FDA is an agency established by a federal law, there are clearly defined pathways along which a drug can be approved. Deciding on the appropriate regulatory pathway for your drug development program is a process that requires an understanding of the content and purposes of sections 505(b)(1) and 505(b)(2) of the Federal Food, Drug, and Cosmetics (FD&C) Act.

The 505(b)(1) Regulatory Pathway

The 505(b)(1) regulatory pathway is the traditional New Drug Application (NDA).  This pathway is used by sponsors to obtain the approval of a new drug whose active ingredients have not previously been approved.  As you can imagine, this type of submission requires extensive research including both clinical and nonclinical studies to prove the product’s safety and efficacy for the indication being sought.  Because of the substantial amount of research and data that is required, 505(b)(1) NDA submissions can take many years to complete, and require a significant amount of resources to get approved.

The 505(b)(2) Regulatory Pathway

The 505(b)(2) regulatory pathway is another type of NDA submission that can be used to obtain the approval of a new drug.  This type of submission differs from the 505(b)(1) NDA in that the product in question contains similar active ingredients to a previously approved drug.  As such, the data included in the submission can rely, at least partially, on the Agency’s findings of safety and effectiveness related to another product.

For example, if a sponsor reformulated a drug so that it can be taken in liquid form instead of tablet or capsule form, the company could use the 505(b)(2) pathway to minimize the amount of original data it would need to submit in support of its new drug. The FDA could rely upon existing data showing that the reference drug is safe and effective, allowing the Agency to focus its attention on determining whether the changes made to the new drug alter its safety or efficacy.

Sponsors taking advantage of the 505(b)(2) regulatory pathway can experience a shorter drug development program that requires less resources than the 505(b)(1) regulatory pathway.

Choosing the Appropriate Regulatory Pathway

When deciding which regulatory pathway is best for your NDA submission, the following questions should be considered:

  • Does the product consist of a New Chemical Entity (NCE)?
  • Is the product a new or novel formulation?
  • If it is an existing product, is it a new route of administration?
  • Does any published literature exist?

While this is by no means an all-inclusive list, answering these four questions will help you to determine which regulatory pathway is most appropriate for you and your product, which is a critical step in the development and submission of an NDA.

If your regulatory strategy guides you down the 505(b)(1) route, you must develop an application that includes all information necessary to prove the safety and efficacy of your new active ingredient. This process will take time and guidance, and supporting information will need to be generated through clinical studies that you must conduct.

If, however, your regulatory strategy guides you down the 505(b)(2) route, your time to market will likely be shorter because you are able to rely, in part, on data from existing reference drugs.

Whichever route you take, it is important to know that the standard of approval is the same. All NDAs are judged with a risk-benefit analysis that doesn’t change because the source of the data supporting the analysis is different.

Benefits of Having a Regulatory Consultant

Choosing the right regulatory pathway is critical to the success of your submission. It is of the utmost importance that you take all precautionary measures to ensure that you are headed in the right direction.  We can help you do this.  The Weinberg Group has significant experience in helping our clients determine the most appropriate regulatory pathway, and then develop and submit the application to the FDA.

Using our unique approach that combines vast regulatory experience with a deep scientific knowledge, we have had overwhelmingly high success rates when dealing with the Agency.  By partnering with us, some of the benefits you will receive include:

  • Experience – we have been working directly with the FDA for more than 35 years.
  • Knowledge – we know what is required to achieve a successful interaction with the Agency, and are uniquely qualified to work with you in preparing and submitting an extraordinary submission.
  • Diversity – our team of scientific and regulatory experts specialize in a variety of disciplines and stay abreast of changing and trends and current events within the industry. Because of this, we are able to bring a unique and extensive range of knowledge and experiences to the table, which is exactly what is needed to develop an application that will be successful.

Regardless of which regulatory pathway fits your development plan best, we’ll be there to ensure that your discussions with the FDA are properly framed to fit the chosen pathway and guide your product through the approval process.

The Weinberg Group:  Expert Guidance for 505(b)(1) & 505(b)(2) Submissions

After developing your regulatory strategy, you know which new drug pathway – 505(b)(1) vs. 505(b)(2) – to use to take your product to market.  For those taking the 505(b)(1) route, The Weinberg Group will help you develop your application, including all information necessary to prove the safety and efficacy of your new active ingredient. This process will take time and guidance, and supporting information will need to be generated through clinical studies.

On the other hand, if you are planning to submit a 505(b)(2) application, your time to market will be remarkably less due to the fact that you are able to rely, in part, on data from existing reference drugs. Our staff will work with you to ensure your product only differs from an approved drug in the following ways:

  • Dosage form
  • Strength
  • Route of administration
  • Substitution of an active ingredient in a combination product
  • Formulation
  • Dosing regimen
  • Active ingredient
  • New molecular entity
  • Combination product
  • Indication
  • Rx/OTC monograph
  • Naturally derived or recombinant active ingredient
  • Bioinequivalence

Afterwards, we will guide you through the entire 505(b)(2) application, using our vast knowledge of and past experience with the FDA to create a seamless filing process.

To learn more about how The Weinberg Group can help you navigate FDA’s regulatory landscape, contact us today.