Pharmacy Practice in Focus: Health Systems
The FDA reviews NDAs and BLAs to approve medications for sale and marketing in the US with decisions required by the PDUFA date.
Since 2015, the FDA has approved an average of 47 new medications each year. In 2024, there were 50 new drugs, with 48% approved as first in class; additionally, 52% received orphan drug designation targeting rare diseases, and 66% used one or more expedited programs, including fast track designation, breakthrough therapy designation, priority review designation, and accelerated approval.1
The Federal Food, Drug, and Cosmetic (FD&C) Act was passed by the US Congress in 1938. The act granted authority to the FDA to regulate the safety of food, drugs, medical devices, and cosmetics. This legislation replaced the Pure Food and Drug Act of 1906 and was introduced following the death of more than 100 patients who ingested elixir sulfanilamide.2
In 1944, the Public Health Service (PHS) Act was enacted, providing a legislative framework for the provision of public health services. This act encompasses biological products and defines them as a “virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, and analogous product, applicable to the prevention, treatment, or cure of a disease or condition of human beings.” Biologics also meet the definition of drugs under the FD&C Act.3
To ensure that medications marketed in the US are safe and effective, the FDA’s Center for Drug Evaluation and Research (CDER) reviews new drug applications (NDAs). CDER oversees both prescription and nonprescription or OTC drugs, with
OTC drugs being brought to the market following the NDA process or through an OTC monograph. It is the responsibility of the company seeking approval to analyze the medication and subsequently submit supporting evidence for review.4 This evidence is derived from data collected from human clinical trials, including information on safety, efficacy, dosages, indications, and drug metabolism of a medication. Based on this research, the FDA decides whether to approve the application to market the medication.5
Types of applications submitted to CDER include investigational new drug, NDA, abbreviated NDA, OTC drug, and biologic license application (BLA).6 This article specifically focuses on NDAs and BLAs.
NDAs are the formal requests that drug sponsors submit to the FDA for approval of new pharmaceutical agents for sale and marketing in the US.7 Biological products, a subset of drugs, are regulated by both CDER and the Center for Biologics Evaluation and Research. These products fall under the FD&C Act but are licensed under the PHS Act, and a BLA is required for biologic products that need licensure under the PHS Act.3 The primary goal of both NDAs and BLAs is to provide sufficient evidence for the FDA to make critical decisions regarding the medication.
Key decisions by the FDA for NDA/BLA submissions include the following7:
Changes to NDAs or BLAs, such as updates in packaging, labeling, inactive ingredients, or indications, are handled through supplemental applications, referred to as sNDAs and sBLAs. A medication would require an NDA or BLA if it was changed to have a different active ingredient, different route of administration, or different dosage forms that would necessitate an additional clinical trial to establish efficacy and safety. These are still approved through CDER, with changes incorporated into labeling and prescribing information, and the drug can then be marketed and prescribed according to the updated and approved changes.8
The Prescription Drug User Fee Act (PDUFA) was created by Congress in 1992 and collects user fees on human drug applications for review, including applications for approval of a new drug submitted under the FD&C Act or licensure of certain biological products of the PHS Act (Table 1).9,10 PDUFA was introduced to address concerns over the FDA’s ability to review and approve drugs in a timely manner. Congress reauthorizes PDUFA every 5 years (currently PDUFA VII), providing an opportunity to enhance the program.
Prior to the PDUFA, average approval decision times were between 21 and 29 months. The time is now half that, with 10 months being the average. For drugs designated with priority review, the timeline is reduced to 6 months from when the application is accepted.11 Priority review designations are granted to medications that provide treatment of disease states that previously did not have any available options or may offer major advances in treatment.5
PDUFA dates refer to the latest date by which the FDA must respond to NDAs or BLAs.12 Once the FDA accepts a filing for the approval of a drug, the agency must complete its review process within 6 or 10 months, depending on whether the application was designated as a priority or standard review.5 Overall, the PDUFA date serves as the anticipated FDA approval date, if approved (Table 2).12-14
The FDA approved benzgalantamine (Zunveyl; Alpha Cognition Inc), a novel oral therapy, for the treatment of Alzheimer disease, on July 26, 2024. The manufacturer submitted the NDA on September 27, 2023, with an original PDUFA date of July 27, 2024—10 months from submission. Studies demonstrated that benzgalantamine, a prodrug previously known as ALPHA-1062, achieves the same therapeutic effects as galantamine with improved gastrointestinal tolerability and without the incidence of insomnia impacting adherence and patient quality of life.1
The FDA’s decision regarding injectable nivolumab and hyaluronidase (Opdivo Qvantig; Bristol Myers Squibb) was made on December 27, 2024. This decision was made 2 days in advance of the PDUFA date of December 29, 2024, which had moved up from its original date of February 28, 2025. Nivolumab, a PD-1 immune checkpoint inhibitor used to treat several types of cancer, is currently administered as a 30-minute intravenous infusion every 2 to 4 weeks. However, the BLA sought approval to administer the medication subcutaneously. This approval makes nivolumab the first PD-1 inhibitor approved for subcutaneous administration, which would be more convenient for patients.13
After reviewing NDAs or BLAs, the FDA may either approve the application or issue a complete response letter (CRL). A CRL is a regulatory action indicating that the application cannot be approved in its current form. This decision may arise from concerns related to key factors such as safety and effectiveness, labeling, or Good Manufacturing Practices. In response, drug companies have several options: they can withdraw the application, request a hearing, or resubmit the application after making the necessary updates.15
A total of 16 medications in 2024 received a CRL due to various reasons. Most recently, Lykos Therapeutics received a CRL for its midomafetamine-assisted psychotherapy for posttraumatic stress disorder, with a request to provide additional phase 3 trial data examining safety and efficacy.14,16,17 Regeneron Pharmaceuticals, Inc, was also issued a CRL for linvoseltamab in relapsed/refractory MM due to a preapproval inspection at a third-party manufacturer, with a plan for reinspection by the FDA.17 Both parties will need to submit additional information required for the FDA to reconsider approval of these medications.
Julie B. Sibbesen, PharmD, is a clinical pharmacy specialist, enterprise medication use, at WVU Medicine in Morgantown, West Virginia.
Jeanette Rich, PharmD, is a clinical pharmacy specialist, enterprise medication use, at WVU Medicine in Morgantown, West Virginia.
The FDA’s drug approval process involves several key components and essential information for evaluation. To initiate the review of new medications, drug sponsors submit NDAs or BLAs. This allows the FDA to assess the drug’s safety and effectiveness, packaging labeling, and manufacturing processes. The FDA is required to decide by the established PDUFA date, which can be either 6 or 10 months after submission. If the application is approved, this date becomes the official approval date. However, if a CRL is issued, sponsors can either withdraw their application or resubmit it for review.
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