FDA Product-Specific Guidelines Guide Proper Evaluation of Generic Bioequivalence in Key Oncology Drugs

On May 21, 2026, the FDA published new product-specific guidances for the development of generic versions of multiple drugs like avutometinib potassium; defactinib hydrochloride (Avmapki Fakzynja), carboplatin, dordaviprone hydrochloride (Modeyso), imetelstat sodium (Rytelo), mirdametinib (Gomekli), selumetinib sulfate (Koselugo) and zanubrutinib (Brukinsa).¹

The newly published guidelines aim to properly guide clinical trials in evaluating the bioequivalence of investigational generic drugs to reference listed drugs. Product-specific guidelines for each drug seek to establish bioequivalence with the most sensitive, accurate, and reproducible processes available according to 21 CFR 320.24 regulations.

Keep reading to see snapshots of how the regulatory agency suggests each drug be developed to best establish therapeutic and bioequivalence to reference listed drugs.

What are the new FDA product-specific guidelines for investigating generic hematologic malignancy drugs?

Zanubrutinib

• The FDA suggests 2 types of studies, one fasting and the other fed, that are single-dose, 2-treatment, 2-period crossover in vivo studies with pharmacokinetic end points to best establish bioequivalence of generic zanubrutinib formulations with oral zanubrutinib tablets.² Both trials suggest studying 160-mg doses of zanubrutinib in patients who are either healthy males or non-pregnant, non-lactating females. Additionally, both studies are recommended to establish bioequivalence on 90% CIs.
• Safety recommendations
  • Exclude patients with abnormal complete blood counts, liver function tests or electrocardiograms, or those who have received or plan to undergo elective surgery, including dental procedures, at least 1 week prior to or following the study
  • Regularly monitor infections throughout the study
  • Regularly use effective contraception for patients who are females with reproductive potential or patients who are male with female partners of reproductive potential throughout the study until 1 week after their final dose

Imetelstat Sodium

• The FDA suggests conducting comparative characterization studies that support active ingredient sameness or requesting a waiver of in vivo bioequivalence studies to properly evaluate the bioequivalence of intravenous (IV) generic imetelstat sodium.³
• Comparative characterization studies suggested by the FDA are identified as studies evaluating either nucleotide sequencing or physicochemical properties.

What are the new FDA product-specific guidelines for investigating generic drugs in breast and gynecologic cancers?

Carboplatin

• The FDA suggests requesting a waiver of in vivo bioequivalence study requirements for evaluating IV generic carboplatin at doses of 20 mg/2 mL, 80 mg/8 mL, or 500 mg/50 mL (10 mg/mL).⁴
• In order to qualify for a waiver of in vivo bioequivalence study requirements, generic carboplatin solutions should be qualitatively and quantitatively the same as reference listed drugs. If generic carboplatin solutions differ from reference listed drugs regarding preservatives, buffers, or antioxidants, developers can still apply to waive study requirements if said differences prove to not affect the efficacy or safety of the drug.

Avutometinib potassium; defactinib hydrochloride

• The FDA suggests a single-dose, 2-treatment, 2-period crossover in vivo study with pharmacokinetic end points to properly establish bioequivalence for oral tablets of generic avutometinib potassium.⁵ The suggested study outlines using EQ 0.8–mg base or EQ 200–mg base doses of generic avutometinib potassium and including patients who are healthy females without reproductive potential. The study also suggests evaluating bioequivalence at a 90% CI.
• Safety recommendations
  • Exclude patients who have a history of risk factors for serious retinopathy or retinal vain occlusion, or who have abnormal ophthalmic exam findings
  • Give prophylactic medications to patients that do not interact with avutometinib or bioanalytical methods to analyze the plasma concentrations of avutometinib
  • Recommend that patients use appropriate sun protection and have limited sun exposure in efforts to prevent dermatologic adverse effects (AEs)
• The FDA suggests a single-dose, 2-treatment, 2-period crossover in vivo study to properly establish the bioequivalence of generic defactinib tablets. The suggested study uses EQ 200–mg base doses of generic defactinib tablets in patients who are healthy females without reproductive potential. The study also recommends evaluating bioequivalence of generic defactinib with a 90% CI.

What are the new FDA product-specific guidelines for generic treatments in neurologic malignancies?

Dordaviprone hydrochloride

• The FDA suggests a single-dose, 2-treatment, 2-period crossover in vivo study with pharmacokinetic end points to properly evaluate the bioequivalence of oral generic dordaviprone hydrochloride tables.⁶ The suggested study uses EQ 125–mg base doses of generic dordaviprone hydrochloride tables and includes patients who are healthy and without reproductive potential. The study also recommends using a 90% CI to evaluate the bioequivalence of generic dordaviprone.
• Safety recommendations:
  • Use effective contraception throughout the study and for 1 month following their last study dose for patients who are male with female partners who have reproductive potential

Mirdametinib

• The FDA suggests either requesting a waiver of in vivo testing based on documented high solubility, permeability, or rapid dissolution of generic mirdametinib, or a single-dose, 2-treatment, 2-period, crossover in vivo study with pharmacokinetic end points to properly evaluate the bioequivalence of oral generic mirdametinib capsules.⁷ The suggested study has a dose of 2 mg and includes patients who are healthy males or healthy females without reproductive potential. Additionally, the suggested study uses a 90% CI to evaluate the bioequivalence of generic mirdametinib.
• Safety recommendations:
  • Exclude patients who have abnormal ophthalmic exam findings
  • Use effective contraception throughout the study and for 3 months following their last dose for patients who are male with female partners with reproductive potential

Selumetinib sulfate

• The FDA suggests fasting or fed studies that are both single-dose, 2-treatment, 2-period crossover in vivo studies to properly evaluate the bioequivalence of oral generic selumetinib sulfate granules.⁸ The suggested study suggests using EQ 25–mg base doses of generic selumetinib sulfate administered as 5 5-mg capsules of granules. Both studies should include patients who are healthy males and non-pregnant, non-lactating females.
• Safety recommendations:
  • Exclude patients who have a history of or risk factors for ophthalmological abnormalities like retinopathy
  • Use non-hormonal contraception in patients who are female and effective contraception throughout the study and 1 week following their last dose in patients who are male with female partners with reproductive potential
• Study recommendations:
  • Oral granules of selumetinib sulfate should be carefully opened and sprinkled within 1 to 3 teaspoons of smooth yogurt or fruit puree.

References

1. Product-specific guidances for generic drug development. News release. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/scripts/cder/psg/index.cfm
2. Draft guidance on zanubrutinib. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_218785.pdf
3. Draft guidance on imetelstat sodium. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_217779.pdf
4. Draft guidance on carboplatin. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_219921.pdf
5. Draft guidance on avutometinib potassium; defactinib hydrochloride. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_219616.pdf
6. Draft guidance on dordaviprone hydrochloride. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_219876.pdf
7. Draft guidance on mirdametinib. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_219389.pdf
8. Draft guidance on selumetinib sulfate. FDA. May 21, 2026. Accessed May 21, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_219943.pdf