Teriparatide Injection's Generic Approval and FDA Quality-Related Review

Introduction to Teriparatide and its Generic Approval

Teriparatide, a peptide-based drug consisting of 34 amino acids with a molecular weight of 4117.8 daltons, is primarily indicated for treating osteoporosis. Its formulation comes as a clear solution in a multi-dose injector pen for subcutaneous injection. Teriparatide is administered daily in a dose of 20 µg for 28 days. The original reference listed drug (RLD) for Teriparatide is Forteo™, developed by Eli Lilly and Co.

In November 2023, the FDA approved the first generics of Teriparatide injection, manufactured by Teva Pharmaceuticals and Apotex Inc. Both these generics, synthesized from a synthetic API, demonstrated equivalence in terms of quality and formulation to the RLD, complying with regulatory guidelines for generic drugs under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).

Key Learning Objectives

The review of Teriparatide generic applications highlights two critical objectives:

Quality-Related Recommendations: To ensure the generic drug meets quality standards, which include the active ingredient’s sameness, proper dosage form, and bioequivalence.
Common Deficiencies: To identify areas where generic drug applicants may face challenges in receiving FDA approval, particularly in peptide drug formulations.

Therapeutic Equivalence: Pharmaceutical and Bioequivalence

For a generic drug to gain FDA approval under the ANDA (Abbreviated New Drug Application) pathway, it must prove therapeutic equivalence with the RLD. This equivalence is based on:

Pharmaceutical Equivalence: The generic must have the same active ingredient, dosage form, strength, and route of administration as the RLD.
Bioequivalence: According to CFR 320.22(b)(1), bioavailability studies for injectable, parenteral solutions like Teriparatide may be waived if they match the active and inactive ingredient concentrations of the RLD.

FDA Guidance on Peptide-Based Generics

The FDA’s 2021 guidance outlines a clear path for generic approvals of synthetic peptide drugs, including Teriparatide, under section 505(j) of the FD&C Act. The guidance emphasizes two critical areas:

Active Ingredient Sameness:This involves rigorous analytical methods to ensure the generic peptide matches the RLD in its primary sequence, physicochemical properties, and higher-order structures.
Comparability Studies:These studies ensure the generic drug’s structure and biological activity are consistent with those of the RLD. Comparisons include the peptide’s sequence, aggregation profile, and biological activity.

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Resource Person: Shubham Sonu