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Globalization Intensifies The Need For Standardized Tests To Ensure Safe Drugs

Mon, 03/24/2008 - 5:55am

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Test chambers for constant climatic conditions are ideal for carrying out mandatory stability tests
Globalization has many advantages. Products and services are available worldwide, and consumers are given a multitude of choices. At the same time, standards have to be adapted and synchronized in order to ensure uniform quality and safety parameters. In this context, the safety of drugs represents a particularly sensitive area.

Here is an example of how this works in practice: The DiapharmGroup is an alliance of consulting and service companies, which is active in the pharmaceutical and health products industry. It specializes in drugs and congeneric products such as nutritional supplements, medical products and cosmetics.

The DiapharmGroup portfolio covers the complete lifecycle of products. Designated specialists handle the various aspects beginning with the product concept through to development, chemical analysis, preclinical and clinical aspects, regulatory questions, risk analysis, including routine chemical analysis, pharmacological vigilance as well as complete lifecycle management.

The Zentralinstitut Arzneimittelforschung GmbH [Central Institute for Drug Research] is the service laboratory of the DiapharmGroup and is responsible for the quality control of its products. It is certified in accordance with Good Manufacturing Practice (GMP) and authorized for approving the release of drugs to the market pursuant to the Arzneimittelgesetz [German Drug Law]. Among the main activities of the service laboratory are:

* Method development

* Method validation

* Quality control for the release of drugs

* Stability testing for certification and/or registration, and as part of pharmacovigilance.

These activities are used to ensure drug safety and consequently the safety of patients. Quite a challenge in terms of globalization, since the development and production of drugs are no longer performed at one location but rather spread around the globe. In addition, markets are no longer confined to a specific continent, but instead are globally diversified.

In terms of pharmaceutical analytics, the results from research, development and production must be comparable, reproducible and comprehensible worldwide. Manufacturers' shelf life data have to be substantiated for an extremely wide range of climatic conditions with respect to transportation, storage and trading conditions.

Within the scope of pharmaceutical analytics, stability tests are being applied pursuant to ICH guidelines, in which drugs are subjected to defined climatic conditions over specific time periods in accordance with a globally harmonized standard. Here, the quality of products can not change, or only within narrow limits. In addition, the so-called organoleptic aspects which are perceived by patients initially, such as odor, taste and the "look and feel," play a role.

This applies both for drugs with chemically defined ingredients as well as for vegetable products (e.g. essential oils) and all administrative forms such as solutions, juices, sprays, transdermal systems, creams, ointments, capsules and tablets.

The stability tests according to ICH are performed at the Zentralinstitut Arzneimittelforschung GmbH with KBF series constant climatic test chambers from BINDER GmbH.

The tests according to ICH are a significant component in the process of certification or registration of a product; in this particular case, the stability of a product with respect to a defined climatic condition over a specific time period (shelf life) has to be substantiated.

In addition to the tests for the certification/registration of drugs, the so-called ongoing stability tests have become increasingly important. They are a part of the continuous monitoring of the quality of drugs in accordance with Good Manufacturing Practice (GMP). Here it must be substantiated that the pharmaceutical product has the necessary stability (quality) for the indicated shelf life period. At the same time, any negative impact on stability, for instance through change of suppliers, should be detected, or even better, be prevented in the first place. Since 2006, the EU-GMP guideline stipulates new obligatory specifications for the preparation of product quality reviews and the ongoing stability testing incorporated in them. Consequently, as part of periodic inspection, the regulatory authorities also focus on the special equipment required for stability testing, in this case, primarily on chambers for constant climatic conditions.

Between 5 and 15 product batches are stored in each constant climate test chamber, where they are exposed to defined climates for specific time periods. The climatic data of the test chambers are completely recorded without interruption.

In order to keep the climate in the test chambers as constant as possible, door openings are kept to a minimum. On the other hand, it is important that the climatic parameters in chambers for constant climatic conditions are restored to the required level as quickly as possible after a door has been opened. Although deviations from ICH climate levels can be tolerated, they must be recorded and the average must not exceed strictly defined narrow limits during the entire time of the stability tests.

BINDER KBF series climatic chambers have formed the basis for all of these stability studies, since no ICH compliant tests can be performed without stable test climates and no GMP compliant handling of test data is possible.

Dr. Sven Oliver Kruse, Managing Director of the Zentralinstitut Arzneimittelforschung GmbH, who uses BINDER test chambers, considers the following criteria to be particularly important:

* Reliability over the entire lifecycle of the climatic test chamber

* Precision

* Compliance with standards.
Reliability and Precision
The test climates pursuant to ICH-Q1A must be maintained reliably and accurately. Stability experiments can extend over a period from three to five years. During this entire time period, climatic chambers must be stable and operate trouble-free.

One of the rules of traceability requires that the quality of the test medium must be better than the quality of the product being tested. BINDER chambers incorporate technologies, such as the APT.line or the Horizontal Airflow Design. The result is that these chambers can achieve natural conditions for environmental simulation to create optimum preconditions for realistic testing while complying with all required test parameters, including specified tolerances.
Compliance With Standards
Another important item is compliance with international standards, in this context specifically ICH specifications; this is absolutely necessary when performing stability tests for approval by the respective national test institutes.

BINDER covers not simply the climatic range in terms of ICH guidelines, but a far larger climatic spectrum. Tests can be run free of humidity at temperatures between -10°C to 100°C [14°F- 212°F]. Climatic testing with humidity covers a temperature range from 10°C to 90°C [50 °F - 194 °F], with a relative humidity range from 10% RH to 90% RH. BINDER KBF chambers moreover maintain constant climatic conditions far more accurately than what is required under ICH guidelines.

The requirements in terms of the GLP/GMP guidelines with respect to recording, processing and storage of measured data pursuant to FDA CFR 21 Part 11 are equally important. This, among other things, also covers the access rights to current measurements as well as stored data.

For this purpose, users can benefit from using the GLP version of BINDER's own APT-COMTM software. The APT-COMTM-GLP software controls and records measured data from up to 30 BINDER units and meets all requirements with respect to data security and validation in terms of FDA CFR 21 Part 11. As an additional feature, the APT-COMTM-GLP software comes with extensive alarm functions, which can also be transmitted via e-mail or by telephone, including transfer into the cellular phone network. This scope of functions is completed with features such as the central control function via TCP/IP, an automatic backup system, as well as an unlimited number of users.
Another Benefit: Photostability
An optional lighting system in accordance with ICH Q1B, Option 2, is available for the KBF chamber for constant climatic conditions. In this case, pharmaceutical products are exposed to defined light quantities from defined lighting sources under constant climatic conditions; in terms of ICH-Q1B, Option 2, separate lighting sources are provided for visible and UV light. Users thus have the advantage of evaluating the effect of visible and UV light on the samples either together, or separately, if necessary.

As an additional option, BINDER offers users its in-house Light Quantum Control feature. With this option, the lighting intensity can be measured conveniently directly at the specific sample location and is integrated into the actual light quantity absorbed in each case online. Once the respective specified individual setpoints for visible and UV light are achieved, the respective lighting sources are switched off individually.

In contrast to traditional light sensors, BINDER - light sensors are not of the planar type, but are spherical. The light intensity can therefore be measured irrespective of the incident angle of the light.

The ICH-Q1B guideline specifies a chemical actinometer for measurement of the exposure dose, which is an ampoule containing a photosensitive solution which converts the absorbed light quantity at a specific rate. This ampoule therefore has an important function, since it is subject to volumetric expansion, just like a pharmaceutical product, in order to provide conclusions with respect to the photosensitive conditions in a medicinal drug. The closest electronic simulation is the spherical measurement with integration through the Light Quantum Control's which BINDER offers as the only source as a method for testing photostability worldwide; BINDER holds a patent for this unique feature.

Stability Chamber Options

With the KBF, BINDER offers users the following options for stability testing:

* KBF basic model for stability tests pursuant to ICH-Q1A

* Lighting system in accordance with ICH-Q1B, Option 2

* Light Quantum Control

This is supplemented and rounded off with a full range of services such as user specific IQ/OQ packages and PQ documentation as well as equipment validation and calibration. Maintenance agreements, a service Hotline, and maintenance service are available either from the BINDER service team or from a qualified service partner. Users thus have global access to a unique package for precise and reliable stability testing in compliance with standards.
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