Biowaiver under SFDA guidelines follows the Biopharmaceutics Classification System (BCS) provision, enabling certain medicines to bypass additional human studies without compromising regulatory standards. The rules are designed to expedite and facilitate the drug registration of eligible medicines, ensuring timely patient access. This approach supports the availability of safe and effective treatments by allowing waivers for certain immediate-release tablets and capsules, balancing strict oversight with practical development timelines.

What is a Biowaiver?

A biowaiver permits the waiver of in vivo bioavailability and bioequivalence studies where in vitro data can justify equivalence. This product development method focuses on highly soluble drugs that have established human absorption profiles and do not have a narrow therapeutic index.

Applicability and Exceptions

Suitable for: Immediate-release, solid oral dosage forms for systemic action if the dosage form is identical.
Not suitable for:
- Dosage forms intended for oral cavity absorption, such as sublingual or buccal tablets, sustained-release, extended-release, or modified-release preparations, cannot be approved without conducting bioequivalence studies.
- Exclude drugs with a narrow therapeutic index, as they require intensive monitoring. This includes medications like digoxin, lithium, phenytoin, theophylline, and warfarin.

Biopharmaceutics Classification System (BCS)

BCS provides a classification of drug substances based on their properties regarding solubility in water and permeability through the intestine:

Class	Solubility	Permeability	Allowance for BCS -based Biowaiver
I	High	High	Eligible
II	Low	High	Ineligible
III	High	Low	Conditionally eligible
IV	Low	Low	Ineligible

Criteria for Biowaiver Eligibility

Solubility

For a biowaiver request, the solubility class boundary is based on the highest strength of the immediate-release (IR) product. A drug substance is considered highly soluble when it achieves complete solubility in ≤250 mL of aqueous media at pH levels of 1.2, 4.5, and 6.8, all at 37 °C.

Permeability

A drug substance is considered highly permeable when the total amount absorbed in humans is 85% or more of the administered dose, as determined by mass balance or comparison with intravenous administration, provided there is no evidence of gastrointestinal instability.

Dissolution

An immediate-release product is fast-dissolving if not less than 85% of the labeled amount of drug substance dissolves within 30 minutes in vitro.
Compare the drug-release profiles of the test and reference products using at least 12 units across three different media, and demonstrate that they are similar.

Excipients

The excipients in the test product should be of the same nature and concentration as those in the reference product, particularly for BCS Class I drugs.
Do not include excipients that affect GI motility or drug permeability, or that interact with membrane transporters, unless you justify their inclusion.
Acceptable excipients to the SFDA should be used here as one of the criteria.
The use of excipients that might affect bioavailability, such as those that impact gastrointestinal motility, complexation, drug permeability, or interaction with membrane transporters, must be avoided unless they have been used in the reference product in the same qualitative and quantitative manner.

Applications of BCS-Based Biowaivers under SFDA

The SFDA permits biowaivers for specific drug applications under the BCS Class I classification. This means a reduced need for in vivo studies, provided conditions for solubility, dissolution, and equivalence are met. The application should include the required information on the excipients as described.

Application Type	Applicable BCS Class	When Biowaiver Applies	Conditions & Requirements	Notes
New Chemical Entities (NCEs)	BCS Class I	After in vivo bioavailability is established.	1) IR solid oral dosage form. 2) Pharmaceutical equivalence between the two formulations. 3) Rapid & similar dissolution.	Not applicable for initial BE waiver; intended only for BE studies (not food-effect or other pharmacokinetic studies)
Generics	BCS Class I	At the time of generic registration	1)High solubility & high permeability 2) Fast dissolution 3) Pharmaceutical equivalence with reference product.	Most frequent biowaiver use in KSA
Post-Approval Changes Variations	BCS Class I	For major changes in the formulation or composition	Pre/post version changes: products have to be pharmaceutically equivalent, rapidly dissolve, and have a similar in vitro profile.	Justification required in variation submission

Fees for Biowaiver Submissions

The SFDA does not charge a separate fee for submitting a biowaiver. Instead, it charges the applicable fee for the specific type of regulatory submission, such as for the registration of a generic drug or a post-approval variation.
Refer to our SFDA Fees guide for a breakdown of all applicable fees for new applications, variations, and scientific advice.