USP Advisory Panel Re-issues Draft USP General Chapters on Topical & Transdermal Drug Products Dissolution Testing into PF 35(3)

By Theo Kapanadze

Today, I would like to draw your attention to a couple of recent changes to the USP Dissolution Testing monograph that you may need to be aware of.  Two new draft USP General Chapters on Topical and Transdermal Drug products have been published in the Pharmacopeial Forum Vol. 35, No. (3) May-June 2009.  The General Chapters are: <3> Topical and Transdermal Products-Product Quality Tests; and <725> Topical and Transdermal Products-Product Performance Tests.  You can find these if you follow the links provided above.

These are important developments since dissolution testing is plying a very important role in the pharmaceutical industry during drug development, quality control and stability programs.

The test is used in order to assure consistent product (batch) quality within a defined set of specification criteria and all products must pass to be on the market.

Initially, the dissolution testing procedure was developed for immediate release solid oral dosage form products and later it was extended for extended/controlled/modified release solid oral dosage form products.  Recently, the application of dissolution testing has widened to a variety of “novel” or “special” dosage forms, such as suspensions, orally disintegrating tablets, chewable tablets, chewing gums, transdermal patches, semisolid topical preparations, suppositories, implants, injectable micro-particulate formulations, and liposomes.  It is referred to as the “drug release test”.

Until now, because of significant differences in formulation design among these novel/special dosage forms, it was not possible to develop a single test protocol that could be used to study the drug release properties of all products.  Rather, different apparatus, procedures, and techniques have been employed on a case-by-case basis.  The two new draft USP General Chapters on Topical and Transdermal Drug products have been published in Pharmacopeial Forum 35(3) May-June 2009 to address this need.

These two General Chapters are part of a series of chapters that will cover product quality and performance tests for the five routes of administration.  In addition to the transdermal route, the other routes of administration include injection, mucosal, inhalation, and gastrointestinal.  The Draft General Chapter <3> is the first in the default monograph series.  For oral dosage forms (gastrointestinal), <711> and Dissolution, <724> Drug Release are examples of product performance chapters.

The general Chapter <725> covers the apparatus and procedures used to evaluate the in vitro drug release and proposes a performance verification test to assess equipment performance.  The product performance test is consistent with that proposed in the FDA Guidance for Industry, Nonsterile Semisolid Dosage Forms, Scale-up and Postapproval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vitro Bioequivalence Documentation (SUPAC-SS).

All this information has been posted on the USP web site.  Comments and suggestions for these tests and procedures are invited from interested parties through the routine Pharmacopeial Forum comment process.  I encourage everyone who may be affected by this to participate.

Reposted from DiTeba Research Laboratories Inc.

Dr. Theo Kapanadze, D.Sc., Ph.D. Chief Scientific Officer, Executive VP Science Dr. Kapanadze is a co-founder of Diteba Research Laboratories Inc. He has more than 30 years experience as an academic researcher, university professor and leading research scientist at major Canadian pharmaceutical and CRO companies.

Read Full Post »

Adapting new analytical technologies with scientific expertise

Dr. Theo Kapanadze

Implementation of new analytical technologies plays a crucial role in designing and controlling manufacturing processes for raw, in-process materials and final product quality. Introduction of new analytical initiatives helps build quality into the product and manufacturing processes, as well as continuous process improvement.

As Charles Darwin told us, it is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.  Both the FDA and industry experts expect benefits over conventional manufacturing practices: higher final product quality, increased production efficiency, decreased operating costs and better process capacity. Correspondingly, fundamental changes are also expected within the analytical services CRO’s which have to modernize their analytical capabilities, scientific expertise and compliance/regulatory standards.

The future of pharmaceutical production will require innovative technological approaches and more science-based processes. Introduction of a new generation of analytical technologies will boost collaboration between research and development and manufacturing departments both inside companies as well as with analytical CRO’s and increase overall efficiency. Approvals and inspections will increasingly focus on scientific and engineering principles. As a result, regulators will set higher expectations for new products from the outset.

Pharmaceutical companies are facing growing demands for increased productivity and reduced manufacturing costs. They also have to meet the evolving need for higher quality standards and higher drug expectations. Therefore, the role of independent analytical experts and CRO’s equipped with the new technology is significantly increasing. The cost factors (affordability) and the higher scientific throughput of the new technologies that have recently been introduced dictate that manufacturers build closer collaborations with specialized analytical CRO’s.

In recent years, a trend of change has been observed within pharmaceutical industry. As modern drug discovery has reached a remarkable level of complexity and drugs need to be discovered, developed and produced against strict timelines and within cost and regulatory constraints, industry seeks “lean”solutions to increase productivity. Among them, increasing the sample throughput of the ever-growing number of necessary (routine) analyses has become a popular target to cut costly time.

For the last thirty years, High-Performance Liquid Chromatography (HPLC) has been the leading technology when it comes to various analyses in the pharmaceutical industry.  However, the necessity of serial analyses taking typically 10-45 minutes has been a sample throughput-limiting barrier.

Lately, the fundamentals of HPLC have been exploited to raise new technologies that can speed up analyses to ground breaking limits, without compromising separation efficiency. The Ultra-Performance Liquid column with 1.7μm particle size handling pressures up to 15000 psi and High Temperature Liquid Chromatography (HTLC) have the potential to take liquid chromatography to the next level in pharmaceutical industry. As each analytical method has its own demands, the advances of the above technologies has different applications in pharmaceutical analysis where high-throughput analysis can be meaningful, as in drug discovery, development and in quality operations. Both chemical and biological pharmaceuticals have considered the perspectives of these technologies and their realizations up to now in high-throughput pharmaceutical analysis.

Since its introduction to the pharmaceutical industry, liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) has played an important role in pharmacokinetics and metabolism studies at various drug development stages. Newly introduced techniques such as Ultra-Performance Liquid Chromatography offer improvements in speed, resolution and sensitivity compared to conventional chromatographic techniques.

Accurate quantification of pharmaceuticals in biological fluids facilitates the correct determination of the pharmacokinetics of a medicine. Low-systemic-exposure compounds such as inhaled products or those undergoing extensive metabolism require very high sensitivity assays to accurately define the elimination phase of the pharmacokinetics curves. This need challenges the sensitivity of modern LC/MS/MS instrumentation.

The recently lunched Xevo TQ-S is an ultra-high-sensitivity tandem quadrupole mass spectrometer. It is equipped with StepWave optics featuring a revolutionary off-axis ion source design. The design of this source significantly increases the efficiency of ion transfer from the source to the quadrupole analyzer while the off-axis ion path eliminates neutral contaminants. These two factors combine to dramatically increase the sensitivity of the LC/MS/MS system.  Also, very valuable results have obtained by capillary electrophoresis and MALDI-TOF mass spectrometry for GLP studies of macromolecules in biological matrices.

Reposted from DiTeba Research Laboratories Inc.

Dr. Theo Kapanadze, D.Sc., Ph.D. Chief Scientific Officer, Executive VP Science Dr. Kapanadze is a co-founder of Diteba Research Laboratories Inc. He has more than 30 years experience as an academic researcher, university professor and leading research scientist at major Canadian pharmaceutical and CRO companies.

Read Full Post »