PARTICLE SIZE DISTRIBUTION AND ANVISA: RELATIONSHIP AND IMPORTANCE

• What is ANVISA's position regarding PSD analysis?
• Is the IFA particle size test mandatory?
• Is it mandatory to indicate the methodology used?

Both the size and the distribution of the particles in the final product indicate important parameters to be carefully evaluated in the process of registering new products on the market. As one of the most mentioned within the industry, the inadequate size and distribution of the particles can lead to a decrease in the degree of dissolution of the final product, causing losses in functionality, bioavailability and efficiency. This size naturally varies according to the sample being studied and its application.

On the other hand, when poorly distributed, the particles can start a process of agglomeration and non-uniform population density, causing different possible reactions of the same product to the final consumer.

A particle size distribution analysis (PSD) necessary for the vast majority of samples to be approved by the National Health Surveillance Agency (ANVISA), whether in the sector of medicines or cosmetics. The problems caused by these parameters, however, are bigger and more diverse than those portrayed in this article. Some affected factors cited by ANVISA are: uniformity of content; stages of the manufacturing process (processability); stability and appearance.

PSD ANALYSIS FOR THE PHARMACEUTICAL INDUSTRY

Aware of these concerns, the regulator requires that the PSD (Particle Size Distribution) is carried out in order to document the physicochemical information of the analyte.

In the Registration of Active Pharmaceutical Inputs (IFA) process, governed by RDC Nº 57/2009, ANVISA clarifies some points as to what is required in this regard.

What is ANVISA's position regarding PSD analysis?

As commented on in the topics above, PSD analysis can be decisive for the study of the IFA dissolution rate, especially for those considered not highly soluble. As it is directly related to the pharmacokinetic profile of the drug, ANVISA considers this analysis to be relevant for the consideration of the quality of the final product, where it is indicated in resolution No. 57/2009. [[top]

Is the IFA particle size test mandatory?

Yes, except in cases where there is a technical justification for the absence of such data. If it is understood that the IFA has its properties influenced in some way by the size and distribution of its particles, the PSD test will be mandatory. In addition to solid samples, the same goes for suspensions, emulsions and aerosols. Otherwise, where there is no specification for particle size distribution, the manufacturer of the IFA may exempt itself from presenting the data. [[top]

Is it mandatory to indicate the methodology used?

Yes, the agency requests the presentation of the method used when registering the IFA. Since the methodology depends on properties inherent to the substance itself, and a method may offer more accurate results than others, the indication of the method is requested. [[top]

As could be seen earlier, it is necessary to have a technical judgment on the need for PSD analysis for each substance. Usually, this analysis is more than necessary, and the lack of this may result in a future requirement from the Agency. It is also important that the methodology to be used is appropriate for the intrinsic properties of each sample.