Biowaiver Eligibility for Injectable Formulations

For injectable formulations, biowaiver eligibility depends on several factors, including the type of injectable (solution, suspension, emulsion), formulation differences, and regulatory guidelines from agencies like the USFDA, EMA, and WHO. Here are the general biowaiver requirements for injectable projects:

Biowaiver for Parenteral (Injectable) Solutions

For biowaivers to be granted for injectables, the formulation must meet specific criteria:

(A) Aqueous Solutions for Intravenous (IV) Use

• Identical API concentration and formulation (excipients, pH, osmolarity)
• No surfactants or complexing agents affecting drug solubility/permeability
• Same route of administration (IV)
• No excipients that impact bioavailability (e.g., cyclodextrins, polymers)
• Comparative physicochemical properties (pH, osmolarity, viscosity)

In vitro equivalence tests, including:

• Assay & Impurities
• pH & Osmolarity
• Viscosity (if applicable)
• Particulate Matter & Sterility
• Extractable Volume & Stability

(B) Non-Aqueous Solutions for IV or IM/SC Administration

• Same qualitative & quantitative composition of excipients
• No change in vehicle or solubilizing agents
• No new complexing agents affecting drug absorption

Biowaiver for Suspensions, Emulsions, and Lyophilized Products

Injectable suspensions and emulsions require bioequivalence studies unless:

• The drug is in true solution after administration
• No excipient changes that impact solubility/dissolution
• No alteration in particle size or polymorphic form

Lyophilized powders (for reconstitution):

• Same API concentration & composition post-reconstitution
• Identical reconstitution medium
• No new excipients affecting bioavailability

Regulatory Guidelines for Biowaiver of Injectables

• USFDA (21 CFR 320): Allows biowaivers for solutions if composition is identical and no excipients affect bioavailability.
• EMA: Requires Q1 (qualitative) and Q2 (quantitative) sameness for solutions.
• WHO Biowaiver Criteria: Similar to EMA/USFDA but allows minor excipient variations if justified.

In Vitro Comparative Testing for Biowaivers

If a biowaiver is pursued, in vitro comparative testing is crucial:

• pH & Osmolality (within acceptable physiological range)
• Particulate Matter & Sterility
• Container Closure Compatibility
• Dissolution/Reconstitution Properties
• Stability Profile Comparison

Conclusion

Biowaivers for injectables are most feasible for aqueous IV solutions with identical formulations. For suspensions, emulsions, or non-aqueous solutions, bioequivalence studies are generally required unless justification is provided based on in vitro equivalence and excipient similarity. Regulatory acceptance varies by composition, administration route, and impact on bioavailability.

Read also:

• Biowaiver for BCS Class 1 Drugs
• Biowaiver for Topical Dosage Forms
• Biowaiver Criteria for Multiple Strengths Across Regulatory Bodies

Resource Person: Moinuddin syed. Ph.D, PMP®