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505(b)(2) Development Articles and Insights

In the News: Regulatory and Development Updates

Rare Disease Clinical Trials Most Often Terminated Due to Regulatory and Recruitment Issues The difficulty associated with successfully completing rare disease clinical trials is well-known. Most people believe that recruitment is the primary reason because, by definition, the number of potential trial participants is extremely

Repurposing Drugs As an Answer to the COVID-19 Crisis

Hydroxychloroquine. The world rallied around this old drug as a potential treatment of COVID-19 patients. The pharma industry, independent researchers, and governments rushed to conduct trials to see if hydroxychloroquine is safe and effective at any stage of this invasive virus. Though it has now

Three Keys to Preparing Effective Pre-IND Meeting Questions

Updated on: April 19, 2021 Asking the appropriate questions during a pre-IND meeting with the FDA is a critical step in planning a development program. A Pre-Investigational New Drug Application (pre-IND) meeting can be a valuable component in planning a development program. For companies that

2019 505(b)(2) NDA Approvals in Review

In 2019, CDER approved 64 NDAs that used the 505(b)(2) pathway, representing important advances in patient care across a wide range of therapeutic areas. The number of 2019 NDA approvals that used the 505(b)(2) pathway fell from 75 in 2018 to 64 in 2019 (Figure 1), in

ANDAs Prioritized to Combat Opioid Crisis

As part of nationwide efforts to address the opioid crisis, FDA is taking a closer look at the development of critical medications that combat overdose deaths. Most recently, FDA announced its intention to prioritize review of ANDAs for drug products indicated for emergency use in

Is the 505(b)(2) or ANDA Pathway Right for Your Product?

Last week, FDA published new guidance, Determining Whether to Submit an ANDA or a 505(b)(2) Application (CDER, 2019), to help Sponsors select the best abbreviated approval pathway for their product. While the guidance does not provide any monumental new initiatives, policies or approaches, here are four key

The New Reality of Generics under GDUFA

From recent news, we know that the FDA has been under increasing pressure to reduce the timing of its reviews while maintaining the highest possible standards for safety and efficacy of the products it approves. This is the reason for the PDUFA and now the

505(b)(2) Approval Times: The Real Scoop

The Approval Time for 505(b)(2) and 505(b)(1) NME Products Is Similar A recent article by the Tufts Center for the Study of Drug Development (summarized here) reported that approval times for New Molecular Entities (NMEs) approved via the 505(b)(2) pathway are nearly 5 months longer

Referencing a Listed Drug for the 505(b)(2) Pathway

Section 505(b)(2) of the Food, Drug, and Cosmetic Act describes a 505(b)(2) new drug application (NDA) as an application 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

505(b)(2) Application Changes: What You Need to Know

Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 was enacted in order to address concerns that had potential to delay access to more affordable drugs. The FDA has been implementing the MMA via the statute since it was enacted

Improving Drug Development ROI in 2017

Time to Pick the Low-Hanging Fruit: Improving Drug Development ROI in 2017 With forecasts of decreasing peak sales for late pipeline drugs, a logical way to increase the return on investment (ROI) for pharmaceutical companies is to develop products with lower research and development (R&D)

Back to Basics: 505(b)(2) FAQs Part 1

As the 505(b)(2) expert, Premier Consulting is frequently asked questions about how to get a product approved via the 505(b)(2) regulatory pathway and if this pathway is appropriate. Given the growing popularity of the 505(b)(2) pathway for approval of repurposed, reformulated, or unapproved marketed products,

Pediatric Applicability or Not–This Revised Guidance Is for You

Since 1994, the statutory and regulatory requirements for drug product labeling for pediatric populations have been evolving. The FDA Modernization Act of 1997 (FDAMA) contained incentives for conducting pediatric studies on drugs that had exclusivity or patent protection. In 2003, the Pediatric Research Equity Act

Additional 505(b)(2) Benefits: Selective Safety Data Collection

Last month CDER/CBER released a short, final guidance, “Determining the Extent of Safety Data Collection Needed in Late Stage Premarket and Postapproval Clinical Investigations.” (CDER/CBER, 2016) While brief, the guidance could provide a significant reduction in safety data collection for NDA sponsors. This could be

3-Year Exclusivity May Not Be Worth as Much as You Think

It is a widely held tenet that market exclusivity is essential for the successful launch of a new drug. But is this always the case? For products approved through the FDA 505(b)(2) pathway, is pursuing the 3-year period of exclusivity available through Hatch-Waxman always necessary?

Enforcement Activities: FDA removes unapproved prescription ear drops

For years FDA has threatened to remove unapproved products (so-called DESI products) from the marketplace. Recently, the FDA took enforcement action against  several unapproved prescription ear drops.  What products will be next?  DESI producers can use the 505(b)(2) pathway to avoid such actions on their products. Let’s take a

Examining the Amarin VASCEPA Saga

The headlines and newscasts reported Amarin’s success in wining off-label promotion, but behind the scenes, another noteworthy action took place – in a very rare action, the FDA rescinded a special protocol assessment (SPA) that would have enabled Amarin to promote the new indication. In

To List or Not to List – That is the Question

A 505(b)(2) may rely on the FDA’s previous findings of safety and efficacy  of an approved drug product. It is possible to rely on more than one approved drug product.  It is also possible that a 505(b)(2) applicant does not have to rely on any approved

Pediatrics – What are the appropriate age ranges?

As we have noted in this blog previously, under the Pediatric Research Equity Act (PREA), all new drug applications for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration are required to contain an assessment of the

MAPPing out the timing of a Complete Response submission

A type of FDA document which sometimes slides past under the radar is  MAPP, that is, Manual of Policies and Procedures.  These are actually internal FDA documents which are generally analogous to the SOPs FDA requires that industry have and follow.  However, by virtue of

Extending Exclusivity: How Long Will It Really Last?

Last week at the Generic Pharmaceutical Association (GPhA) Annual Meeting, the 21st Century Cures Act, a proposed bill with bipartisan support, was a topic of discussion. Specifically, subtitle L—Dormant Therapies, which would offer 15 years of exclusivity for drugs and biologics approved as dormant therapies.

Therapeutic Equivalence Ratings Under 505(b)(2)

The FDA listing of therapeutic equivalence (TE) ratings can be a murky area for products approved under 505(b)(2) applications. The concept of TE ratings emerged from FDA regulations for generics and revolve around the announcement that the FDA would publish a current listing of all

5-Year Exclusivity for Certain Fixed-Combination Drugs with an NCE

The FDA recently posted new guidance on its website awarding certain fixed-combination drug products (fixed-combinations) 5-year new chemical entity (NCE) exclusivity. While the Agency held previously that these products were ineligible for NCE exclusivity (5 years) if one component is already approved, with this new

Alkermes Prodrug for Treatment of Multiple Sclerosis: NCE?

The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease).

Paper Submissions: Going, going…away

In order to fulfill a requirement specified in Section 745A(a) of the Food and Drug Administration Safety and Innovation Act (aka FDASIA), FDA recently issued a draft guidance directing mandatory use of electronic filing and formatting for most regulatory submissions which currently can still be submitted

ANDA but No NDA – What to Rely on?

Premier Consulting participates in multiple pre-IND (PIND) meetings each month and one thing we notice in the FDA minutes is that the boilerplate answer to ‘does the Agency agree this ….. is appropriate for filing under 505(b)(2)?’ keeps getting longer.  Recently, the Agency (or, at

PREA – Pediatric Plan Timing Changed by PDUFA V

The Food and Drug Administration Safety and Innovation Act (FDASIA; also known as PDUFA V), signed into law on July 9, 2012, contains amendments to the Pediatric Research Equity Act (PREA) that specifically detail the timing of the submission of a Pediatric Study Plan (PSP). In

New PDUFA V Meeting Timelines

PDUFA V ushered in new industry and FDA commitments. Among these are changes in meeting timelines. A significant change from PDUFA IV is the timeline for Type A meetings. Under PDUFA IV the meeting package was due 30 days in advance of the meeting. Now,

Are 505(b)(2)s “Super Generics,” or what do we call them?

When Premier Consulting was young, products approved under 505j were called “generics” and 505(b)(1) “new drugs.” There was no consensus name for products approved via 505(b)(2). Of course, at the time there had been very few 505(b)(2) products approved. By now, we have seen an

No 5-Year Exclusivity for Combinations Drugs with an NCE

One anomaly to the exclusivity rules is that a combination drug product containing a new chemical entity (NCE) and one or more previously approved drugs does not receive the 5-year exclusivity that a single-component NCE drug would receive. Thus, Ferring Pharmaceuticals Prepopik (sodium picosulfate, citric

Orphan Designation without Exclusivity: Court asked to decide

Yesterday, Depomed filed suit against the FDA requesting the Court to order FDA to grant their product Gralise (gabapentin) seven years of exclusivity since it was granted Orphan status; upon approval, Gralise was granted three years of exclusivity. Depomed licensed the product to Solvay which became

ViroPharma Denied Request for 3-year Exclusivity

ViroPharma has pulled out all stops to prevent generic copies of its off-patent Vancocin® capsule (vancomycin hydrochloride) including the use of the Citizen Petition process. Recently, FDA denied most of the requests in their Citizen Petition and simultaneously approved generics from 3 companies. ViroPharma immediately

Drug Development Planned Like the Titanic

How many drug development companies leave it up to the CMO to design or execute their formulation and manufacturing without oversight? Like those who boarded the Titantic 100 years ago, they seem to trust the mantra that their contractor’s work is unsinkable. MAP Pharmaceuticals seemed

Generic vs. 505(b)(2) Failure-to-Warn Liability

A recent editorial (may need subscription) in the New York Times opined that a recent Supreme Court decision – a “bizarre outcome” – “makes it virtually impossible to sue generic manufacturers for failing to provide adequate warning of a prescription drug’s dangers.” The court case the

When is an IND required?

Most of us know that a BA/BE study of a generic can be done without an IND (the exception, called a Bio-IND, is when the drug being studied is cytotoxic or a radioactive labeled drug). In 505(b)(2) drug development we often are studying the BA/BE

Labeling for Abuse-Deterrent Drugs

From a technological standpoint, it is understood that the goal of developing 505(b)(2) abuse-deterrent products is to make changes to the API or formulation of a drug that has abuse potential in such a way that it dissuades the abuser from wanting to use the

Target Product Profile

In any project development program an understanding of the program goal is critical to finding the shortest path to the final result. Generation of a Target Product Profile early in a development program facilitates reaching the goal of a marketed drug product. It provides a

505(b)(2): Repositioning, Repurposing or What?

Some define repositioning as the process of examining alternate indications for drugs that have failed in the clinic. Others say that repurposing (with or without the hyphen; re-purposing) is interchangeable with repositioning. When many people think of repositioning drugs, they expect the outcome to be

FDA’s Determination of Vyvanse as NME Upheld

On March 4, 2010 the U.S. District Court for the District of Columbia agreed that FDA was within its rights to grant Shire’s Vyvanse (lisdexamfetamine dimesylate) NME status and thus, 5-years exclusivity. New Rivers Pharmaceuticals (NRP) was the original sponsor of the lisdexamfetamine NDA. During the

505(b)(2) Approval Standards – Referenced Studies

Awareness of current FDA standards and those of its various divisions is important when preparing a new submission. A basic premise for a 505(b)(2) submission to the Agency is that the application contains full reports of investigations of safety and effectiveness. However, for 505(b)(2) applications, at least

Reference Listed Drugs (RLDs): Can More Than One Be Used?

Can a 505(b)(2) NDA have more than one RLD? In a word, the answer is “yes.” When using the 505(b)(2) regulatory pathway, sponsors may rely on the agency’s previous findings of safety and/or efficacy of an already approved product which is termed the reference listed

REMS or RiskMAP or what?

On 30 September 2009, the FDA issued a new draft guidance for industry: Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications. The guidance describes the content and format of a REMS, which the FDA was authorized

Comparability Protocols

What do you need to do when you need to change suppliers or manufacturing sites? Among the many choices is a formal FDA comparability protocol. Advance planning can improve the possibility that the FDA accepts your proposed change. One alternative that can streamline the process

DESI Products: Q&A

The FDA is moving against DESI drugs and DESI producers are wondering if their products are next on the chopping block. Here are a few commonly asked questions about how that will affect DESI producers. Will a 505(b)(2) of a DESI receive exclusivity? Yes, the

Test Specifications for Stability Studies

Pivotal stability programs that are used to generate stability data for NDA submissions are different than research stability programs used to design the drug product, explore packaging configurations, etc. This is common sense, but we have seen instances of pivotal stability programs that have been

ANDA Suitability Petition vs 505(b)(2)

I was honored to be invited to speak at the FDA-OCRA 12th Annual Educational Conference in Irvine California on June 10, 2009.  I was asked to discuss and compare the 505(b)(2) and ANDA Suitability Petition.  I thought I should share this topic with the readers

Risk Evaluation Mitigation Strategy (REMS) for long-acting opioids

The Food and Drug Administration (FDA) heard testimony on May 27 and 28, 2009, regarding the effort to develop a class-wide Risk Evaluation Mitigation Strategy (REMS) for long-acting opioids products that contain fentanyl, hydromorphone, methadone, morphine, oxycodone or oxymorphone. The public hearing was held to

What are DESI Drugs?

DESI drugs are a great source for 505(b)(2) development since many will qualify for 5 years data exclusivity. In this post, we will define what they are. Once upon a time…. In 1938 the FD&C Act was established that required that drugs be proven safe

Multiple Dosage Strength Products – CMC Considerations

Developing a product with multiple strengths? How do you go about filing multiple strengths in an IND? How and when do you draft one CMC section covering multiple drug strengths for the same dosage form? Long-term drug development goals may include multiple strengths of a

505(b)(2) NDA Labeling

A draft label be included with all NDA submissions. For a 505(b)(2) NDA, where do you get the information for this label? What labeling is required? What is labeling? Well, the “label” is what is on the immediate container of the drug product and can

505(b)(2) Literature Searches – Too much or too little?

A 505(b)(2) submission relies on information in the public domain to fulfill some of the information required in an NDA for approval. This information comes from more than the reference drug’s NDA review documents. In fact, for older drugs, the amount of information can be

PREA and 505(b)(2)

Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the

What Is the Competition for Your Product?

In speaking with sponsors, we often discuss the potential competition to their proposed drug product. In order to have success in the market, the proposed product needs market differentiation. Existing products What other drugs are available for the same therapeutic indication(s)? Why would the medical

Paragraph IV Certifications under 505(b)(2)

What is the difference between a Paragraph IV certification between the 505j (ANDA, generic) and 505(b)(2)? None.  The difference is the exclusivity outcome – 505(b)(2) never gets any exclusivity based on patent certification. In a U.S. drug application, in Module 1, Administrative Documents, you must

505(b)(2) Patent & Marketing Exclusivity

IP attorney Stephen Albainy-Jenai and I just concluded a webinar hosted by DIA entitled 505(b)(2) Patent & Exclusivity.  23 different companies attended, showing the increasing interest in 505(b)(2) issues.  Earlier this year, DIA hosted my overview of the 505(b)(2) drug development process where the attendees had many questions asking