Inhalation formulations provide rapid and direct access to the lungs through localized administration, reducing the dose administered and increasing efficacy. Inhalation formulations can be classified as dry powder inhalers (DPI), metered dose inhalers (MDI), nebulizers, and sprays depending on the device. Inhalation is the preferred mode of administration for the prevention and treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, due to the special features of the dosage form, device and mode of action as compared to ordinary formulations, research into generic inhalation formulations is difficult.
Our Services
As a professional generic conformity assessment company, Alfa Chemistry specializes in providing comprehensive and detailed services to clients in the field of inhalation formulations to ensure that generic drugs match the RLD in terms of safety, efficacy and quality.
Regulatory Consulting and Support
- Project development consulting: conducting gap analysis for clients' proposed projects.
- Regulatory interpretation: interpretation of the requirements of drug regulatory agencies in different countries and provision of customized solutions to clients.
- R&D strategy consulting: providing consulting services to clients on drug development and market access.
- Regulatory guidance: providing clients with regulatory counseling and document preparation services during the drug registration process.
Pharmacological Equivalence Evaluation
We select the appropriate RLD according to the guidelines of the client's region, and use it as a reference to conduct the following pharmacological studies on generic inhalation formulations to ensure consistency with the RLD:
- Qualitative and quantitative analysis of active ingredients
- Selection and dosage of excipients
- Formulation process study
For the process prescription, we give full consideration to the particle size, dispersion state, ratio and binding mode with the carrier, as well as the control of water and environmental humidity of the raw and auxiliary materials.
Bioequivalence Evaluation
The bioequivalence evaluation requirements for generic inhalation formulations vary in different regions, and the following are examples from FDA and EMA.
The FDA recommends the use of the weight-of-evidence method for BE studies. This method judges equivalence based on all data obtained from appropriate in vitro studies, PK studies and PD studies. Similarities in prescribing and delivery devices are considered while ensuring equivalence and patient adherence to the replacement drug. To conclude that a generic drug and RLD are bioequivalent, the four elements of similarity in prescribing and delivery devices, equivalence in in vitro testing, equivalence in PK studies of systemic exposures, and equivalence in PD and clinical studies must be met simultaneously, otherwise bioequivalence is not established.
The EMA guidelines use a stepwise assessment approach to the bioequivalence evaluation of inhalants. This approach uses in vitro studies as the first step, and if the results of the in vitro studies meet the specific equivalence criteria, bioequivalence between the two agents can be determined directly. If the results of the in vitro study do not meet the bioequivalence criteria, a PK study is required, which includes an assessment of pulmonary and systemic bioavailability. If the PK study results still do not meet the equivalence criteria, a third step uses PD and clinical endpoint studies to demonstrate local bioequivalence. If bioequivalence can be demonstrated by PK studies, no further large-scale PD and clinical efficacy studies are required.
Our team of experts is well versed in the bioequivalence evaluation guidelines for inhalation formulations in major countries/regions around the world, and provides compliant and efficient bioequivalence evaluation services to our clients.
Application Preparation and Submission
Our company has successfully completed a number of conformity evaluation cases and has rich experience in generic drug development and submission, and we are skilled at completing the data organization and submission process in accordance with the latest requirements of the guidelines.
For most of the inhalation preparations, it is a special preparation which is a kind of medicine and equipment in one, so the requirement for the linkage of medicine and equipment is high. Through our professional technology platform and rigorous validation process, our company provides efficient and reliable generic consistency evaluation services for inhalation formulations, and helps the products to be marketed smoothly.
