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A structured overview of critical formulation, physicochemical, and performance attributes required to establish equivalence with the Reference Listed Drug (RLD
In the development of suspension dosage forms for bioequivalent generics, bridging with the Reference Listed Drug (RLD) requires comprehensive evaluation of formulation, physicochemical characteristics, and performance attributes. The first step involves confirming Q1/Q2 sameness, where the generic product must contain the same qualitative (Q1) and quantitative (Q2) composition as the RLD. This includes matching the active ingredient (in the same salt, ester, and crystalline form), as well as excipients such as suspending agents, preservatives, sweeteners, buffers, and flavoring agents in both type and concentration. For suspensions, preservative efficacy testing becomes crucial, especially in multi-dose presentations.
Beyond composition, achieving Q3 equivalence requires the comparison of key physicochemical attributes. These include pH, which affects both drug solubility and stability; viscosity, which impacts dose uniformity and ease of redispersion; and particle size distribution (PSD), a critical parameter influencing suspendability, physical stability, redispersibility, and, in some cases, bioavailability. Other essential tests include sedimentation volume, specific gravity, appearance, osmolality (for pediatric or sensitive routes), and content uniformity. Evaluating redispersibility is particularly important, as the product must remain uniformly suspended and re-suspend with minimal shaking.
The container-closure system must also be comparable to that of the RLD in terms of material (HDPE, glass), closure (child-resistant, induction sealed), and functionality of the dosing device (oral syringe, spoon, or dropper). Functional equivalence of the dosing apparatus is often reviewed critically by regulatory agencies. Additionally, the generic product must undergo stability testing under ICH guidelines to ensure consistent performance over shelf life. For multi-dose systems, microbial testing and preservative efficacy must be validated to maintain microbiological quality.
If the product meets Q1/Q2/Q3 criteria, it may be eligible for a biowaiver, particularly if the API is BCS Class I or III and systemic exposure is not required. However, if a bioequivalence (BE) study is mandated, it is typically performed under fasting conditions (and fed, if labeled so), with appropriate pharmacokinetic sensitivity to detect systemic levels. In some cases, local gastrointestinal action may require additional justification or clinical endpoint studies.
Overall, suspension bridging requires a holistic strategy—focusing on formulation sameness, in vitro performance, container compatibility, and clinical relevance—to ensure therapeutic equivalence and regulatory approval under the ANDA framework.
Read also:
- QTTP, CQA, CPP and CMA of Liquid Dosage Form
- Formulation Development Strategy for BCS Class IV Molecules
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