European Medicines Agency (EMEA) has issued a concept note on the revision for guidance on quality of modified release oral dosage forms and transdermal dosage forms. The regulatory authority will await for comments before October 2010 on the Section 1 of the document.
The proposed guideline will alter existing guideline: CPMP/QWP/604/96.According to a communication from the EMEA, the Note for Guidance (NfG) on modified release products addresses specific quality requirement for modified release products, particularly the in vitro testing.
The NfG focus primarily on oral dosage forms including both prolonged and delayed release formulations. However there is room for further guidance particularly in relation to the choice of the appropriate dissolution test and media, details on the development of in vivo/in vitro correlation and new technologies. Since the requirements for transdermal dosage forms are only briefly described in the document. As such, a more elaborated chapter on transdermal patches is needed in this guideline with special focus on the interchangeability aspects for generic transdermal patches, stated the EMEA communiqué .
The main topics during the revision of the guideline in the context of modified release oral dosage forms are: The functionality of the excipients and its role in drug release mechanism which should be considered. The choice of the appropriate dissolution test in terms of media and hydrodynamics. The use of new technologies to provide in- vitro and in-vivo relationships based on performance of individual dosage form units. Quality by Design for dissolution specifications for evaluation of generics and interaction of alcohol with modified release oral dosage forms which may lead to "dose dumping".
Oral formulations are still the most common pharmaceutical dosage form, even among the newly introduced drugs, and will probably continue to be in the next few years. Several Modified Release (MR) technologies which includes hydrophilic matrix tablets, osmotic systems, and coated multiparticulates) are well established and understood.
In vitro dissolution test is often used during development and quality control as a predictive tool to indicate changes which may have an effect on the efficacy or safety of the product.
In addition, the new quality paradigm Quality by Design and new technologies can be used to provide in vitro-in vivo relationships based on the performance of individual dosage or dissolution specifications. Since there is an interaction of alcohol with modified release oral dosage forms containing strong opioids which lead to "dose dumping" of opioids for some (generic) products, it has become necessary to review the requirements for in vitro or in vivo data for all modified release products. This has led to provide further guidance and elaborate the specific requirements, according to EMEA.
The recent scientific developments and increased number of transdermal patches applications for marketing authorisation, has forced EMEA to further illustrate the specific requirements for this dosage form. The concept of generics and interchangeability of transdermal patch formulations has generated the need for further clarification and guidance, according to EMEA.
The revision of the guideline in the context of transdermal dosage forms are the Skin adhesion which has recently a major issue for TDDS1 and should be therefore carefully addressed. Patch load versus drug released particularly when the active substance poses a risk for drug abuse besides the patch size and its implications on skin adhesion.
The Quality Working Party recommends the revision of NfG. Clear guidance will facilitate regulatory approval and help industry during the development of these products.