The FDA wields a supreme amount of power in the regulatory realm of the pharmaceutical industry. For smaller start-ups or those newer to the industry, navigating the compliance pathways can prove a daunting task.
The relationship between pharmaceutical companies and the Food and Drug Administration (FDA) has often been a difficult one, with some drugmakers feeling stymied by the agency’s influence on the process of getting a new drug to market.
Essentially, the FDA is responsible for holding companies to account and ensuring the efficacy, safety and security of drugs and biological products. Of course, thousands of potentially unsafe drugs have been blocked before reaching the public, but some have questioned the extreme regulatory scrutiny applied by the FDA over the years.
In December 2022, congress gave the FDA more powers to hold drugmakers accountable as part of a mammoth spending bill. For example, the agency now has explicit authority to make drug companies have confirmatory studies to get accelerated approval. This increased leverage over pharmaceutical companies has meant for newer companies to the industry it may seem a rather daunting task to get a drug approved.
We sat down with the FDA’s own Charles Kohler who works as a Press Officer for the Centre for Drug Evaluation and Research. Informed by experts, Kohler explains how start-up companies might go about getting their drug to market and what the FDA looks for when deciding upon approval.
The process
Tom McGhie: How soon in the process should a pharmaceutical company “get in touch”?
Charles Kohler: If a company has identified a specific product and has outlined a clinical development programme, but they have questions in advance of submitting an investigational new drug (IND) application to the FDA, they can request a pre-IND meeting to discuss the content and format of the IND.
TM: What advice would you give smaller start-up pharmaceutical companies who haven’t engaged with the FDA before?
CK: We encourage companies to take advantage of the many public resources and guidance documents FDA makes available on the FDA.gov website. For smaller companies, the FDA also has a CDER Small Business & Industry Assistance (SBIA) website which provides a focused resource for small businesses that provides comprehensive information on drug development.
Keeping up with industry changes
TM: How has advanced manufacturing (automation, etc.) influenced your approval system? Has it sped it up/complicated matters?
CK: Since innovative approaches to manufacturing can present regulatory challenges, CDER created the Emerging Technology Program (ETP) to discuss, identify, and resolve potential technical and regulatory issues facing manufacturers developing and implementing emerging technologies. ETP engagements with manufacturers can occur prior to filing a regulatory submission and even be independent of a specified drug product.
ETP members represent all relevant FDA quality review and inspection programmes including CDER’s Office of Pharmaceutical Quality (OPQ), CDER’s Office of Compliance (OC), and the FDA’s Office of Regulatory Affairs (ORA).
There are no prescribed review timelines for applications submitted during or following ETP engagement other than those related to user fee goal dates. ETP reviews of applications with advanced technologies have yet to miss a user fee goal date. In fact, a recent FDA self-audit found that continuous manufacturing applicants who had early engagement with the ETP to discuss development and implementation had relatively shorter times to approval and marketing as compared to similar batch applications, based on the median times to approval (three months faster) and marketing (four months faster) from submission (see: Fisher AC, et al. An Audit of Pharmaceutical Continuous Manufacturing Regulatory Submissions and Outcomes in the US. Int J Pharm. 2022).
TM: Has there been an impact from the rise of orphan drugs?
CK: While the FDA does not have a way of measuring impact to the public from the rise in orphan drugs, we would hope that the increasing number of products approved for the treatment of rare diseases is having a positive impact on patient communities with previously limited treatment options.
Common mistakes
TM: Are there any common mistakes you see from companies?
CK: There are a few noteworthy common pitfalls that drug developers and researchers may encounter when seeking to market a new drug in the US and applying for FDA approval. These include:
- Insufficient data: One of the most common pitfalls is failing to generate enough data to support the drug's safety and effectiveness. The FDA requires comprehensive clinical data to evaluate a drug before approving it for marketing—referred to as substantial evidence of effectiveness.
- Inadequate study design: Another common pitfall is a poorly designed study, which can lead to flawed results that do not adequately generate data (see first pitfall) to demonstrate the drug's safety and efficacy. Study design must be carefully planned to ensure the data collected is reliable and informative.
- Incomplete or inaccurate labelling: The labelling of a drug is critical to its safe use, and any inaccuracies or omissions can lead to serious harm to patients. The FDA requires clear and accurate labelling that includes information on the drug's risks, benefits, and proper use.
- Inadequate communication with the FDA: Communication between drug developers and the FDA is critical throughout the drug development process to ensure adequate study design and that the necessary data needed to support the drug’s safety and effectiveness will be generated.
- Non-compliance with FDA regulations: Finally, failure to comply with FDA regulations can result in significant delays in the approval process or even rejection of the drug. Drug developers must ensure that all regulatory requirements applicable are met throughout the drug development process, at the time of and throughout marketing.
It's important to note that these are just some of the common pitfalls drug developers and researchers may encounter when seeking FDA approval, and there may be other challenges and obstacles that arise along the way.
TM: Have you seen a move in relationships between manufacturers and FDA from adversarial in the past to a consultative one in the 21st century?
CK: CDER’s role is to assure that high-quality medicines are safe, effective, and available to US patients. In addition to the ETP, CDER has other ways of supporting manufacturers developing certain products for US patients. The user fee programmes emphasise the importance of, and create opportunities for, effective communication between applicants and FDA in driving the development of high-quality drug products. The recently reauthorised user fee programmes include, for example:
- FDA meetings for certain noncompliant facilities to obtain preliminary feedback regarding corrective actions after receiving a warning letter and prior to a reinspection.
- FDA’s early assessment of drug master files (DMFs), up to six months prior to the submission of certain abbreviated new drug applications (ANDAs) or supplements that will reference the DMF.
- A new type of meeting to expand communication and feedback during drug development; in addition to the traditional development meetings (Type A, B, and C), there is now a Type D meeting for quick discussion on a narrow set of issues.
- A new meeting option to facilitate successful Investigational New Drug Applications (Initial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT)).
- A Chemistry, Manufacturing, and Controls Development and Readiness Pilot programme to further expedite the development of products that address unmet medical needs.
