The latest changes we have recommended were presented as In Process Revision articles that appeared in the January-February issue of Pharm. Forum (39(1); 2013). The changes are examined, together with responses to the public commentary on the previous revisions, in an explanatory Stimulus to Revision paper.
The sub-committee has favored moving away from specification setting on the basis that this process is really the task of the regulatory agency. A consensus has emerged that the role of the national/regional pharmacopeias is primarily to provide scientifically sound and robust methodologies that support the provision of safe and efficacious products.
The Aerosols sub-committee is currently considering the collection of all the background information about the complex cascade impactor method into a new informative chapter in the >1000 series, thereby simplifying Chapter 601 still further. The sub-committee also presented in Pharm. Forum (37(4); 2011) a Stimulus to Revision paper proposing that a new informative chapter be developed to cover spacers and valved holding chambers which are used widely with pressurized metered dose inhalers.
There is becoming a regulatory need, in Europe at least, to have standardized methods in place for such products. Late last year, the British Pharmacopeial Commission, in a policy statement, recommended to the European Directorate for the Quality of Medicines and Health Care (EDQM), the governing body for the Ph. Eur., that a monograph covering add-on devices be developed, based on the initial steps taken at the USP in the Stimulus article referred to previously. My hope is to harmonize this work in the regional pharmacopeias and I’m working informally with Dr. Steve Nichols, who sits on the Inhalanda Committee of the Ph.Eur., to achieve this goal.
These topics will be presented in detail at the upcoming AAPS Workshop on Inhaled Drug Products: Current Practices and the Future of In Vitro Testing Technologies and Regulation, which is sponsored jointly by the AAPS Inhalation and Nasal Technology Focus Group (INTFG), the USP, and the FDA. in early September.
Q: What are the best developments in the OINDP industry you have seen in the past few years?
A: In terms of equipment for testing inhalers, I am excited about the potential of a new mixing inlet that was developed many years ago by Dr. Nick Miller (Nephele Enterprises), and is now available through Copley Scientific Ltd. and also RDD Online. This inlet has been used successfully by several groups to separate the constant flow rate requirement for the cascade impactor from the variable flow rate experienced at the inhaler patient interface when testing on a breathing simulator.
A group of former AstraZeneca employees, has just published a paper where they used this inlet in conjunction with a series of anatomically accurate upper airways representing small, medium, and large adult airways, evaluating different inhalers for the delivery of budesonide particles at low, medium, and high flow-rate patterns associated with healthy adults. This study is, to my knowledge, the first to show excellent in vitro-in vivo correlations with different inhaler types for this particular corticosteroid (Olsson B, Borgström L, Lundbäck H et al. J. Aerosol Med. Pulmon. Deliv. 2013;26: Fast Track).
It’s just one drug product; but they were able to get their in vivo/in vitro correlation to apply across DPIs, MDIs, and a jet nebulizer. I encourage everybody to read it as an example of what can be done to improve the measure of agreement between laboratory testing and clinical measures relating to API regional deposition in the human respiratory tract. Their approach also demonstrates with the value of clinically relevant and appropriate testing methods.
