Skip links

In the News: September 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program.

FDA Discusses Focus Areas for PDUFA VII During Public Meeting

Following the August publication of the proposed PDUFA VII commitment letter negotiated with industry, the FDA held its corresponding required public meeting on September 28. The meeting consisted of FDA presentations of the major focus areas included in the commitment letter, industry negotiation participant comments, and public comments. None of the presentations revealed anything new outside of the commitment letter, but some may have indicated areas which the FDA intends to focus on and/or emphasize:

  • The Split Time Application Review (STAR) pilot that seeks to expedite patient access to novel uses for existing therapies to treat serious conditions with unmet medical needs
  • The expanded use of the INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meeting: INTERACT meetings are intended to facilitate IND-enabling efforts where a sponsor is facing a novel, challenging issue that might delay the progress of the product towards entry into the clinic in the absence of this early FDA input.
  • The new Type D meeting, which allows for quicker discussion of a narrow set of issues (no more than two focused topics) between the FDA and a sponsor, such as a follow-up question that raises a new issue after a formal meeting
  • Improved predictability in Human Factors and User-Related Risk reviews
  • Continued development of the use of complex innovative trial designs
  • Facilitating CMC readiness and enhancing communication during CMC review to promote a more efficient and effective process
  • Continue development of the use of Real-World Evidence

Many of the initiatives will not take place immediately, but during the lifespan of PDUFA VII: 2023-2027. Camargo can provide further insight as the process moves forward.

CDER Announces Novel Excipient Review Pilot Program

The Center for Drug Evaluation and Research (CDER) has announced the rollout of the Novel Excipient Review Pilot Program in Federal Register Vol. 86, No. 171. Though novel excipients can provide solutions to difficult development obstacles, sponsors have been hesitant to use them since their acceptability is uncertain. The pilot program is the first step in allowing manufacturers to receive a preliminary review of a novel excipient, prior to drug product formulation.

Eligibility for the pilot program has been limited to excipients that 1) have not been previously used in FDA-approved drug products, and 2) do not have an established use in food. Sponsors may submit proposals for excipients that meet these criteria for preliminary review. The pilot program will proceed in two stages:

  1. During the initial proposal stage, applicants can outline the supportive data gathered thus far along with the public health or drug development need addressed by the excipient. Four proposals will be accepted initially, but more may be accepted for evaluation if adequate resources for review are available.
  2. The sponsors of the accepted proposals will submit a full package consisting of required toxicology and quality data, as outlined in the Federal Register. Upon review of these packages, CDER will provide input on the acceptability of the excipient in the proposed use.

The pilot program is accepting proposals through December 7, 2021. Camargo provides extensive expertise in nonclinical, clinical, and CMC requirements for novel excipients. Our experience can assist in alleviating the challenges associated with novel excipients and empower manufacturers and sponsors to get their life-changing products to the most important place: the patient.

Appellate Court Ruling Impacts Orphan Drug Exclusivity

On September 30, the Eleventh Circuit Court of Appeals issued a decision reversing a district court ruling in a case involving orphan drug exclusivity. The case contains several interesting aspects, including the FDA’s decision to “administratively divide” an applicant’s NDA, but the central issue was whether the statutory phrase “same disease or condition” was ambiguous.

Whether or not the phrase is ambiguous is the first portion of the Chevron test, which is very often used by the courts in suits against the FDA. A short (and overly simple) explanation is that if the court finds the phrase ambiguous, it goes on to review whether the FDA’s actions were reasonable. If the phrase is found to be unambiguous, the analysis stops there (and the FDA often loses the case).

In this instance, the lower (district) court found the phrase ambiguous, determined that the FDA’s actions were reasonable, and found for the FDA. However, the appellate court, determining that the district court had applied an incorrect analysis in making that determination and that the phrase was not ambiguous, found for the appellant. The result is a decision which may significantly expand the extent of an original grant of orphan drug exclusivity. Although this is one case, and the FDA can appeal to the Supreme Court, there may be an impact on the granting of orphan drug designations (ODDs) going forward. Contact Camargo if you are considering an ODD to determine how these changes can affect you.

FDA Issues Controlled Correspondence Q&A for ANDA Sponsors

Many potential ANDA sponsors have first-hand experience with just how particular the FDA can be regarding the format and content of a controlled correspondence. Occasionally, multiple attempts are necessary to properly present a question. However, some relief for those sponsors may be found in a guidance published in September titled “Questions and Answers on Quality Related Controlled Correspondence“:

OPQ [the Office of Pharmaceutical Quality] has observed that the same questions are frequently received in multiple controlled correspondence submissions. These Q&A are intended to proactively respond to those scientific and regulatory topics that appear frequently in controlled correspondence addressed by OPQ, thereby allowing industry to move forward with certain generic drug development activities without the need to submit controlled correspondence to FDA.

The guidance lists questions and answers for the following topics:

  • Bracketing/matrixing
  • Container-closure changes
  • Dissolution microbiology (endotoxin testing)
  • Number of batches
  • Orientation
  • Packaging
  • Scoring and split tablet testing
  • Size and shape of generic solid oral dosage forms

It appears that the FDA intends for the guidance to reduce the volume of controlled correspondence and make life a bit easier for ANDA applicants. If you are developing a generic drug, Camargo has extensive experience with ANDA strategies and FDA interactions and can assist you with your development program.


Bill Stoltman, JD
Vice President, Regulatory Operations

Ryan Key, PhD
Senior Scientist, CMC Services