On February 12th, Tracey Safran, Senior Account Manager and Oksana Olkhovyk, Senior Scientist at Gateway Analytical hosted a webinar for generic drug manufacturers of nasal spray suspensions discussing how the method of Ingredient-Specific Particle Sizing (ISPS) using Raman Chemical Imaging (RCI) developed by Gateway Analytical, can address the critical path opportunity (CPO) by providing the accurate and precise drug particle size measurement to demonstrate bioequivalence.
The presenters also provided information on Gateway Analytical’s process for addressing the critical path opportunity; outlining the development of the feasibility study, writing and implementing the validation protocol, and the sample size needed for analysis as required by the FDA.
For more details on the webinar, you can use the links below.
- View the webinar
- Download the presentation slides
We received a number of questions from attendees during the Q&A segment, and you can find those questions and answers below. If you have any questions about this or any other topic, please contact us.
- How long does it take to go through the CPO process versus completing clinical trials?
The Process provided by Gateway Analytical for the CPO takes approximately 6 to 9 months to complete (from Phase I through Phase III). The time frame is dependent on factors including the number of APIs in the formulation, if agglomerates need to analyzed and how timely the samples are submitted for analysis. - What is the cost savings associated with the CPO?
The cost of completing the 3 phase approach we have taken for the CPO is a fraction of the cost of a PK Study and Clinical trial combined. As you know, these two studies alone can cost millions of dollars. Since each formulation is different, the cost may be different for each customer. We would encourage you to set up a conference call to discuss your particular formulation in order to provide you with a formal quote. - How does RCI differentiate API particles from their agglomerates or from API-excepient agglomerate?
In RCI, a Raman spectroscope analyzes the wavelengths of scattered light emitted by the molecules of every particle in a sample and matches up the spectral information with morphological information. Since each type of molecule emits a characteristic signature, its spectrum can definitively identify the makeup of each individual particle scanned. Resulting optical and Raman Chemical Images enable analysts to correlate the data on a pixel-by-pixel basis, clearly showing which particles consist of API and which are excipients. For further details, please refer to the White Paper: Analysis of Aggregates in Nasal Spray Suspensions - Can you expand on the advantages of treating a nasal spray suspension as a solution, does this require less testing overall?
The FDA regulations for establishing BA/BE for solution formulations are different and less comprehensive than that for suspensions. The specific testing requirements may be found on FDA website. - During this comparative in-vitro testing, do you maintain blinding of samples and whether the blinding procedure is mentioned in the In-vitro protocol?
The ISPS analysis of Blinded samples may be included in Validation study upon customer request. - Is RCI also suitable for DPI analysis?
Yes, we offer ISPS analysis for DPI and MDI formulations using RCI. At Gateway Analytical, highly trained analysts can identify the PSDs of each of the active ingredients found in the fine particle fraction after actuation of the device, the amount of each drug that remains attached to carrier particles, and the number of drug particle aggregates. Please refer to the White Paper: Analysis of Multi-Component Engineered Particles for Inhalation by Raman Chemical Imaging and the White Paper: Using Raman Chemical Imaging to Analyze Inhaled Combination Therapies - Is RCI similar to Malvern’s G3-ID?
The technology utilized for ISPS by RCI is fundamentally different. Wide-field illumination RCI allows for obtaining Raman spectrum in each pixel with high spatial and spectral resolution in conjunction of Brightfield Reflectance image of the same Field of View (FOVs). Imaging modalities are collected in series parallel: Brightfield Imaging then Raman Chemical Imaging for thousands of randomly selected FOVs. FOVs are collected as either: a montage or a coordinate list. Automated data acquisition accelerates the generation of data leading to larger number of particles and the capability of more representative sampling. How this works: Individual API particles are initially identified by their specific Raman spectrum. Each particle is treated with a unique intensity threshold to binarize the Raman chemical image and thus yielding a particle map. A feedback loop is initiated which confirms the chemical identity against the Raman spectrum and validates the particle size against the brightfield optical image. A single particle, for example, may be represented within a 30 pixel x 30 pixel field, with a spectrum collected for each pixel. By associating the spectra of the different chemicals with spectrum of each pixel in the RCI, it is possible to obtain a visual representation of the presence of each of the chemical within each FOV by correlating the data on a pixel-by-pixel basis. - Would you share if the FDA has accepted the in vitro equivalence data (as presented) and if they have given a clinical waiver for any generic program?
The FDA has not shared with us if anyone has submitted their results using RCI for the CPO biowaver at this time. You are welcome to call the FDA office of Generic drug for further information on this topic and they encourage and welcome your calls for further information. - Have you communicate with FDA for this Bio-wavier issue? What are the FDA's comments?
We have a very good working relationship with the FDA and the office of Generic drugs. We have also published a paper with the FDA on this very topic using our RCI technique as discussed in the webinar.