Generally, complex generics are products that have complex active ingredients, formulations, dosage forms, or routes of administration, or are complex drug-device combination products. Generics of complex brand name drugs (i.e., reference listed drugs) can be more difficult to develop. As such, a complex drug may be less likely to have an available generic.
To help patients access important medical treatments, FDA’s Center for Drug Evaluation and Research works to better understand the scientific issues impacting complex generic development and assessment. FDA shares these scientific insights publicly, further enabling generic drug applicants to develop complex products and helping to ensure that applicants have the necessary information to prepare complete submissions.
This page features news, information, and additional resources about FDA’s activities that support the development and approval of complex generic drugs.
Every year, FDA approves or tentatively approves hundreds of generic drug applications, including dozens of complex generics. Below is a list of recent notable complex generic approvals.
- On March 15, 2022, FDA approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol.
- On February 24, 2022, FDA approved the first generic of Apokyn (apomorphine hydrochloride (HCl)) injection, 30 milligram (mg)/3 milliliter (mL) (10 mg/mL).
- On February 2, 2022, FDA approved the first generic of Restasis (cyclosporine ophthalmic emulsion) 0.05% single-use vials.
Below is a list of recent and upcoming events regarding complex generics.
- October 27-28, 2022: Best Practices for Utilizing Modeling Approaches to Support Generic Product Development
- November 3, 2022: Formulation Characterization and Cutaneous Pharmacokinetics to Facilitate Generic Topical Product Development
- December 6, 2022: Excipients and Formulation Assessments of Complex Generic Products: Best Practices and Lessons Learned
- September 20-21, 2022: Advancing Generic Drug Development: Translating Science to Approval
- June 29, 2022: In Vitro Release Test (IVRT) and In Vitro/In Vivo Correlation (IVIVC) of Complex Generic Ophthalmic, Injectable, Implantable, and Inserted Products
- May 9-10, 2022: Generic Drug Science and Research Initiatives Workshop
- April 26-27, 2022: Generic Drugs Forum 2022: The Current State of Generic Drugs
- September 21-22, 2021: Advancing Generic Drug Development: Translating Science to Approval
Guidance documents represent FDA's current thinking on a topic and may discuss more specific products or issues that relate to the design, production, labeling, promotion, manufacturing, and testing of regulated products. Below is a list of recently published guidances and other documents related to complex generics.
- In October 2022, FDA published a revised final guidance for industry, “Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA” This guidance, previously published in November 2020, describes the enhanced pathway for discussions between FDA and a prospective applicant preparing to submit (or an applicant that has submitted) an ANDA for a complex generic drug product to FDA.
- In August 2022, FDA published a new batch of 48 draft product-specific guidances (PSGs). PSGs provide recommendations for developing generic drugs and generating the evidence needed to support abbreviated new drug application (ANDA) approval, thereby helping to streamline generic drug product development by industry and ANDA assessment by FDA. FDA also updated the Upcoming Product-Specific Guidances for Complex Generic Drug Product Development web page, which is updated each time FDA publishes a new batch of PSGs.
- In May 2022, FDA published a new batch of 37 draft product-specific guidances (PSGs). PSGs provide recommendations for developing generic drugs and generating the evidence needed to support abbreviated new drug application (ANDA) approval, thereby helping to streamline generic drug product development by industry and ANDA assessment by FDA. FDA also updated the Upcoming Product-Specific Guidances for Complex Generic Drug Product Development web page, which is updated each time FDA publishes a new batch of PSGs.
- In April 2022, FDA published a new draft guidance for industry, “Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use.” The guidance is intended to assist applicants preparing an abbreviated new drug application (ANDA) by describing how FDA intends to evaluate a request for a waiver, with regard to a pH adjuster, under 21 CFR 314.99(b) of the requirement in 21 CFR 314.94(a)(9)(iii) and (iv).
- In April 2022, FDA published a new Manual of Policies and Procedures (MAPP) 5240.10, “Classifying Approved New Drug Products and Drug-Device Combination Products as Complex Products for Generic Drug Development Purposes.” The MAPP details FDA’s policies and procedures for classifying which approved new drug products and CDER-led drug-device combination products are complex products for generic drug development purposes.
- In February 2022, FDA published a new batch of 43 draft PSGs. FDA also updated the Upcoming Product-Specific Guidances for Complex Generic Drug Product Development web page.
FDA’s GDUFA Science and Research Program provides new tools for FDA to evaluate generic drug equivalence and for industry to efficiently develop new generic products. Below are recent FDA articles focusing on complex generics.
- Effects of Realistic In Vitro Test Factors on the Aerosol Properties of Metered-Dose Inhalers
- Formulating Drug Products for Optimized Absorption: Elucidating Amorphous Solid Dispersions
- How Modeling Was Used to Support the FDA Approval of a Topical Generic Drug Product
- Generic Drugs in the 21st Century: FDA’s Actions Create Transparency and Value for Complex Generic Product Development
Further information on complex generics is available at the links below.
- The Center for Research on Complex Generics
- Product-Specific Guidances for Generic Drug Development
- Upcoming Product-Specific Guidances for Complex Generic Drug Product Development
- GDUFA Science and Research
- Generic Drug Research Priorities and Projects
- FDA Drug Competition Action Plan
- Infographic GDUFA III – Summary of T-Cons and Meetings (PDF - 117 KB)