Over the past 35 years, the Food and Drug Administration’s (FDA) generic drug program has helped increase the availability of affordable, high-quality drugs in the United States. There are now more than 10,000 FDA approved generic drugs and nine out of ten prescriptions in the United States are filled with generic drug products. Generic drugs alone have saved the U.S. healthcare system over a trillion dollars in the past ten years. And while companies find their generic drug applications placed into a rigorous review process at the FDA, they also find Agency assistance that gives them the information they need to be successful.

Developing a generic drug

As most generic drug companies know, the first step in developing a generic drug is to identify what drug product to pursue and to research the most appropriate methodology to make it. The next step is to prepare and submit an Abbreviated New Drug Application (ANDA) to the FDA. The ANDA contains all required information and related documents necessary to support the approval of the proposed generic drug product. Generic drug applications are termed "abbreviated" because they are generally not required to include independent preclinical (animal) and clinical (human) data to establish safety and effectiveness as are brand name drugs. Instead, the ANDA contains data about the drug which the FDA assesses to assure the proposed generic is the same as the brand-name drug it references.

Typically, generic drug applicants must demonstrate, among other things, that their generic drug has the same active ingredient, strength, dosage form, route of administration, and (with certain permissible differences) labeling as the brand name drug. Companies must also ensure the generic drug product is bioequivalent to the brand name drug, and that the generic will be manufactured according to the Current Good Manufacturing Practice Regulations required by the FDA for all drug products.

To assist applicants with meeting the standards of an ANDA application, the FDA’s Generic Drug Program provides an abundance of online information and guidance. The additional good news is that during the past few years, the FDA’s generic drug assessment and approval process has become increasingly efficient, with the number of review cycles and overall time to approval decreasing for newly submitted applications. The FDA has also improved communications with applicants about application deficiencies, which helps applications move more efficiently through the review process.

The following are some of the resources available online at Generic Drug Development.

Pre-ANDA Program

The pre-ANDA Program³ is a valuable information resource that features product development assistance and pre-submission and mid-review cycle meetings for complex generic products to help clarify regulatory expectations early in product development and during application review.

ANDA Forms

Summary tables, application forms, and other ANDA submission resources are available on the FDA website. To ensure submission of a complete ANDA, applicants should review the following forms and prepare all that are required for their specific application. Please note that this is not an exhaustive listing of requirements.

• Filing Review of ANDAs MAPP including filing checklist

• Form FDA-356h: Application to Market a New Drug, Biologic, or Antibiotic Drug for Human Use

• Instructions for using Form FDA-356h

• Form FDA-3794: GDUFA Cover Sheet

• Form FDA-3674: Certification of Compliance

• Instructions for completion of Form FDA-3674

Guidances and other information

Guidance documents represent the Agency’s current thinking on a variety of topics. These documents provide recommendations on the content, evaluation, and ultimate approval of applications as well as the design, production, manufacturing, and testing of regulated products for FDA assessment staff, ANDA applicants, and ANDA holders.

• Generic Drugs Guidances: Search for guidances related to generic drugs by typing “generics” into the search box

• Biopharmaceutics Guidances (Search "Biopharmaceutics" in the box above the table)

• Product-Specific Guidances for Generic Drug Development: to assist the generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating the evidence needed to support ANDA approval, FDA regularly publishes product-specific guidances describing the Agency’s current thinking and expectations on how to develop therapeutic equivalents to specific reference listed drugs 

• Drug Master Files (DMFs)

Laws, regulations, policies, and procedures

The Federal Food, Drug, and Cosmetic Act⁴ is law that sets forth the requirements for drug product approval. Section 505(j) of the law contains the foundational requirements for ANDAs. 

FDA regulations that implement the law are published in the Federal Register⁵ (a daily published record of proposed rules, final rules, meeting notices, etc.) and collected in the Code of Federal Regulations (CFR).⁶ Section 21 of the CFR contains most of the regulations pertaining to food and drugs. The following regulations directly apply to the ANDA process (but is not an exhaustive listing):

• 21 CFR Part 314: Applications for FDA Approval to Market a New Drug

• 21 CFR Part 320: Bioavailability and Bioequivalence Requirements

Edward Sherwood, Director and Captain Vincent Sansone, Deputy Director, Office of Regulatory Operations in the Office of Generic Drugs, U.S. Food and Drug Administration

References

1. https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations

2. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/generic-drug-development

3. https://www.fda.gov/drugs/generic-drugs/pre-anda-program

4. https://www.fda.gov/regulatory-information/laws-enforced-fda/federal-food-drug-and-cosmetic-act-fdc-act

5. https://www.federalregister.gov/

6. https://www.ecfr.gov/cgi-bin/ECFR?page=browse