Exemptions from bioequivalence evaluation (BE) can simplify the approval process for drugs and lower marketing costs. Our company provides BE exemption guidance services for generic drug companies, reducing the need for bioequivalence trial in the drug development process and speeding up the drug marketing process.
Types of BE Exemption
The guidelines issued by various authorities (such as FDA, NMPA, EMA and WHO) on the exemption of BE for generic drugs are roughly divided into the following two types.
Type Ⅰ exemption: The BE trial of a specification shows bioequivalence to the RLD, thereby exempting the BE trial of other specifications.
For this type of BE exemption, the prescribing process for other specification products must demonstrate prescribing similarity. There are three cases of prescription similarity judgment:
- The composition ratios of all active and inactive components are similar among different specifications.
- Meet these conditions:
- The quality of preparations with different specifications is almost the same.;
- Each specification uses the same inactive components;
- The specification is changed by changing the amount of active components and one or more inactive components.
- The proportions of active and inactive ingredients are not similar among products of different specifications, but there is sufficient evidence to support the similarity of the prescriptions.
Type Ⅱ exemption: BE exemption based on the Biopharmaceutics Classification System (BCS).
Introduction of BCS
The BCS system is a widely accepted scientific system for classifying drugs according to their water solubility and intestinal permeability. When it comes to the rate and extent of API absorption in vivo in oral solids, commonly released preparations, the BCS system mainly considers solubility, intestinal permeability, and dissolution.
According to the BCS classification system, drugs are divided into four categories:
Class Ⅰ: High Solubility - High Permeability
Class Ⅱ: Low Permeability - High Permeability
Class Ⅲ: High Permeability - Low Permeability
Class Ⅳ: Low Permeability - Low Permeability
The rate and extent of absorption of BCS Class Ⅰ and Ⅲ drugs does not depend on the dissolution time or transit time of the drugs in the GI tract. Therefore, for drugs in BCS Class Ⅰ and Ⅲ, it is not necessary to demonstrate the possibility of in vivo bioavailability and bioequivalence of the drug, that is, BE exemption, as long as other excipients in the prescription do not significantly affect API absorption.
BCS-based BE exemption conditions
For drugs in BCS Class Ⅰ, the following conditions need to be demonstrated:
- The drug has high solubility.
- The drug has high permeability.
- Both the generic and RLD are rapidly dissolving and do not contain any excipients that could affect the rate and extent of API absorption.
For drugs in BCS Class Ⅲ, the following conditions need to be demonstrated:
- The drug has high solubility
- Both the generic and RLD had rapid dissolution
- Generic drugs and RLD should be prescribed exactly the same, with similar dosages of each component, and when scaled up and changed after marketing, the formulation should be exactly the same
Information for application for BCS-based BE exemption
- Data support (or literature information) of high solubility
- Data support (or literature information) for high permeability
- Data support for rapid dissolution and curve similarity
There are some differences in the requirements and scope of BE exemption for generic drugs among different regulatory agencies. Moreover, excipients, prodrugs and combination preparations may also affect BE exemption. Our company has fully studied and compared the technical requirements of different guidelines, and can provide guidance services for BE exemption for drug manufacturers in different countries or regions to ensure compliance and shorten the time of drug approval to market.
