Biomedical Engineering Reference
In-Depth Information
intrinsic resource-saving potential that is maximized when combined with an AIM-
QC system. However, it is important to appreciate that EDA is also appropriate to
interpret data obtained from a full-resolution impactor. There is no one-size-fi ts-all
defi nition for the boundary size selection process. Each sponsor must therefore do
the due diligence to demonstrate the sensitivity of EDA to detect important changes
in a given product, using their in-house particle size data obtained during the prod-
uct development phase. Such an approach, if undertaken effectively, has the inbuilt
advantage that the full-resolution CI is always available for the management of
investigations, change control, and troubleshooting. A combination of AIM and
EDA can ultimately optimize resource allocation in the product QC environment.
An approach making use of abbreviated impactors based on the AIM-pHRT
design would be more appropriate, if the development of a robust IVIVR in cases
where the clinically relevant sizes are known. Such an outcome could be the ulti-
mate goal of CI-based measurements for the OIP, where the clinical performance of
the product is the primary focus of interest. Such measurements could serve as a
quick indicator that clinically relevant size fractions associated with the product
have not altered during the transfer from development to production phases and also
in the management of intentional changes post-approval.
References
1. European Medicines Agency (EMA) (2009) Requirements for clinical documentation for
orally inhaled products (OIP) including the requirements for demonstration of therapeutic
equivalence between two inhaled products for use in the treatment of asthma and chronic
obstructive pulmonary disease (COPD) in adults and for use in the treatment of asthma in
children and adolescents. London, UK. CPMP/EWP/4151/00 Rev 1 Available at URL: http://
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/
WC500003504.pdf . Visited 27 Sep 2012
2. European Directorate for the Quality of Medicines and Healthcare (EDQM). Preparations for
inhalation: aerodynamic assessment of fi ne particles. (2012) Section 2.9.18—European
Pharmacopeia [− Apparatus B in versions up to 4th edn 2002] Council of Europe, 67075
Strasbourg, France
3. European Medicines Agency (EMA) (2006) Guideline on the Pharmaceutical Quality of
Inhalation and Nasal Products. London, UK, EMEA/CHMP/QWP/49313/2005 Final.
Accessed 20 Jan 2012 at: http://www.ema.europa.eu/pdfs/human/qwp/4931305en.pdf
4. Tougas TP, Christopher D, Mitchell JP, Strickland H, Wyka B, Van Oort M, Lyapustina S
(2009) Improved quality control metrics for cascade impaction measurements of orally inhaled
drug products (OIPs). AAPS PharmSciTech 10(4):1276-1285
5. Mitchell JP, Newman SP, Chan H-K (2007) In vitro and in vivo aspects of cascade impactor tests
and inhaler performance:a review. AAPS PharmSciTech. 8(4):article110. Available at URL:
http://
www.aapspharmscitech.org/articles/pt0804/pt0804110/pt0804110.pdf . Visited 30 June 2012
6. Mitchell JP, Dolovich MB (2012) Clinically relevant test methods to establish in vitro equiva-
lence for spacers and valved holding chambers used with pressurized metered dose inhalers
(pMDIs). J Aerosol Med Pulm Drug Deliv 25(4):217-242
7. Usmani OS, Biddiscombe MF, Nightingale JA, Underwood SR, Barnes PJ (2003) Effects of
bronchodilator particle size in asthmatic patients using monodisperse aerosols. J Appl Physiol
95(5):2106-2112
Search WWH ::




Custom Search