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When is 505(b)(2) a Good Choice for Your New Drug Application?

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Taking a New Drug to Market

When you want to market a new drug and there is enough evidence on the drug’s safety and efficacy, the 505(b)(2) is a desirable regulatory pathway for a New Drug Application (NDA).

Based on the source of studies that support the safety and efficacy of the proposed drug, you’ll most often choose between these three main types of NDAs:

  • 505(b)(1) applications require that all of the safety and effectiveness studies were conducted by the applicant or that the applicant has the right of reference for use of the studies. These applications are also called “stand-alone” NDAs. 
  • 505(b)(2) applications should contain complete safety and efficacy data, but also allow certain safety and effectiveness studies not conducted by the applicant. The applicant does not have the right of reference for use of the information. This can include studies published in scientific literature or findings of a previously approved drug from the public domain. The strength of evidence needed for the safety and effectiveness of the drug is the same as those required for a 505(b)(1) application. The 505(b)(2) is sometimes considered the hybrid of the 505(b)(I) application and the ANDA.
  • Abbreviated new drug applications (ANDAs) under section 505(j) are appropriate for drugs that the FDA has previously approved, such as generic drugs. The applicant must provide information to support that the generic product’s active ingredient is bioequivalent to the Reference Listed Drug (RLD). If any new studies are necessary to demonstrate safety or effectiveness, then the drug would not be appropriate for this type of application. A generic drug 505(j) means the life of the previously approved new drug via 505(b)(1) route has ended. 

Drug Approval Pathways Can Be Cumbersome And Confusing

The 505(b)(2) pathway leads to a prolonged life cycle of a new drug compared to 505(b)(1). This approval route is designed to encourage innovation and eliminate expensive and lengthy duplicative preclinical and clinical studies from the existing new product, which may not have been optimized for the safety and efficacy during the initial 505 (b)(1) period. For example, you can use previously published literature to justify the safety or effectiveness of a drug, which saves both time and resources. 

The types of information can include biochemical, pharmacokinetic, pharmacodynamic, pre-clinical or clinical studies. However, the applicant will still need to conduct some clinical PK/PD bridging studies to have a complete application in most cases.

Another major advantage of the 505(b)(2) pathway is shortened review time by the FDA. Since 2017, 60% of all approved NDA’s were 505(b)(2) applications and the average review time dropped to 10 months. Almost half of the 505(b)(2) products approved in 2017 were submitted by companies with four or fewer approved products in the U.S., and 30% of the approvals led to many companies’ first FDA-approved product. This shows that the 505(b)(2) pathway provides unprecedented opportunities for companies.

Right Of Reference and Market Exclusivity

Both the 505(b)(2) and ANDA allow applicants to use data not generated by themselves and include previously known drugs or molecules. This often causes some confusion on which pathway to select. 

By definition, 505(b)(2) is “an application that contains full reports of investigations of safety and efficacy 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 or use.” 

To be defined as a study conducted by the applicant or for which the applicant has the right of reference, the applicant should either be named a sponsor of the investigation or provide substantial support for the investigation. Alternatively, the applicant may have purchased exclusive rights to a study. 

Another significant difference that sets these pathways apart is the number of years of market exclusivity allowed. The 505(b)(1) grants five years, the 505(b)(2) grants three to five years, and the ANDA grants only six months of market exclusivity. Thus, the 505(b)(2) pathway can expedite the new product’s time to market, minimize development costs and gain three years of market exclusivity. This difference may drive some critical decisions in developing a previously known drug into a new drug.

Ideal 505(b)(2) Candidates

Drugs that fit the 505(b)(2) pathway are usually not entirely novel entities but have not been previously approved by the FDA. For example, a 505(b)(2) would be appropriate for a new indication of a known small molecule, a different mode of delivery of an approved drug, or a combination drug that includes a previously known drug. Between 2012–2016, most 505(b)(2) applications involved drugs with new dosage forms, new combinations, or new formulations.

Ideal drug candidates for a 505(b)(2) application include:

  • Drugs for a new indication from an already approved label
  • New combination formulation of already approved drugs
  • New combination formulation that consists of an already approved drug along with new active ingredients
  • Drugs with a change in dosage, form, strength, or route of administration of an already approved drug on the market. This includes, but is not limited to, oral extended-release formulation, injectables, inhalation, transdermal patches, etc.

On the other hand, the ANDA pathway is suited for drugs that the FDA has already approved. The applicant must demonstrate that the new drug is bioequivalent to the old drug, along with equivalence of active ingredients, conditions of use, route of administration, and so on. 

However, specific differences may be allowed, such as inactive ingredients or omission of an indication. The line between “allowable differences” and “considerable differences” is the key to whether the ANDA or 505(b)(2) is the appropriate pathway for the proposed drug. 

BioPharma Can Help You Navigate The Regulatory Affairs Landscape

In addition to meeting the numerous conditions throughout an NDA, the application process is a long one, and BioPharma can assist you throughout the journey. 

BioPharma’s Scientific and Medical team has extensive experience developing a 505(b)(2) product clinical development plan using the bridging PK/PD study approach. BioPharma also provides advice related to safety and efficacy assessments, and the variety of clinical trials necessary for the 505(b)(2) pathway.

Whether you need a study to establish a new indication for a small molecule or investigate a novel route of delivery for a previously approved drug, BioPharma can provide the services you need and guide you through the appropriate regulatory pathways. 

BioPharma has extensive experience conducting clinical pharmacokinetic studies as a part of 505(b)(2) submissions. The results of these studies may serve as the bridge study for pharmacokinetic response and therapeutic efficacy for your drug. 

Common bridging studies in 505(b)(2) program can include: 

  • Comparing the bioavailability of an existing pharmaceutical moiety with the new product(s)
  • Steady-state comparative pharmacokinetics assessment
  • The effect of food
  • The impact of gender and age
  • Presence of active metabolite(s)

The Highest Standards for Studies

BioPharma Services Inc. is a full-service Contract Research Organization (CRO) staffed and managed by leaders in their fields. BioPharma specializes in conducting Phase I/IIa and Bioequivalence clinical trials for pharmaceutical companies worldwide. Founded in 2006, BioPharma has conducted numerous clinical studies that helped companies navigate complex FDA regulatory pathways. In addition, Dr. John Oldenhof, Chief Scientific Officer at BioPharma, has extensive experience with Canada’s equivalent of the FDA, providing clients with further flexibility on a global scale.

Dr. Nicola Hughes, VP of BioPharma’s Bioanalytical Lab, said, “We really understand that clients put a lot of emphasis and finance into their drug program, and we want to make sure that when we run a study that we do it absolutely perfectly, so I set very, very high standards for our studies.” 

BioPharma’s Bioanalytical Lab is equipped with the latest instruments that demonstrate the bioequivalence of molecules and all the necessary analytics necessary for clinical studies. In addition to services such as Bioanalysis at our GLP- Certified Laboratory and Regulatory Affairs, BioPharma also specializes in Biostatistics and Safety Data Analysis (CDISC), Data Management, and Medical Writing.

About BioPharma Services

BioPharma Services, Inc., a Think Research Corporation company, is a full-service Contract Research Organization (CRO) based in Toronto, Canada, specializing in Phase I/IIa and Bioequivalence clinical trials for international pharmaceutical companies worldwide. BioPharma has clinical facilities both in the USA and Canada with access to healthy volunteers and special populations. 

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