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Verifying efficacy and safety with multipurpose analytical devices

Supporting pharma company development and product quality control

Without medicines, human health maintenance is impossible. Japan’s universal health insurance system allows everyone to receive medical treatment, from hospital diagnosis and drug prescriptions to injections. If a hospital visit is impractical, over-the-counter medicines can be purchased easily through nearby pharmacies or drugstores. For minor ailments, these medicines can alleviate symptoms or prevent them from worsening.

At the same time, since drugs are taken into the body, they have a direct impact on life and health. Consequently, pharma companies are responsible for ensuring drug efficacy and safety. They develop and manufacture medicines ethically, under such strict legal controls as the Pharmaceutical and Medical Device Act. Furthermore, pharma companies aim to provide stable supplies of medicine so that anyone receiving treatment for illness can continue that treatment as long as needed.

Shimadzu analytical technologies support pharma company development and quality control of medicines. Do you know how many years it takes for a single new drug to reach the market? The answer is more ten or more years.

Drug development begins with synthesis of candidate compounds and basic research to determine potential effectiveness. In addition to a compound’s effect on the body, pharma companies must conduct repeated testing to determine the quality of active constituents as well as their formulation. The next steps are verification of absolute efficacy and safety through animal and human clinical trials, research relating to commercialization, and obtaining government approval before placing the drug on the market. At key points throughout this long process, Shimadzu's analytical instruments play an essential role.

Making contributions to drug development, principally by means of liquid chromatography-mass spectrometry

Among the many analytical instruments from Shimadzu that contribute to drug development, Shimadzu’s liquid chromatography-mass spectrometers (LC-MS) are the ones most often used. These measuring instruments combine a liquid chromatograph that separates and analyzes the components of compounds, with a mass spectrometer that ionizes specific substances and measures their mass.

LC-MS technology supports drug discovery by identifying and verifying promising drug candidates from over 100,000 compounds, and in the purification of synthesized compounds. In addition, these instruments can evaluate how drugs make their way through the body, and by measuring drug concentrations in urine and blood, how they are metabolized and excreted.

In addition, at the pre-shipment quality control stage, these instruments play a critical role in a wide range of quality tests, including verification of active constituent levels. Recently, LC-MS technology has been contributing to drug effectiveness testing, disease biomarker detection, and discovery of new medicines to target disease-causing substances.

Besides its liquid chromatographs and LC-MS instruments, other instruments from Shimadzu are active in numerous stages of drug development and manufacturing. These include spectrophotometers for material acceptance testing, total organic carbon analyzers to verify line cleanliness, gas chromatograph-mass spectrometers to measure levels of residual solvents in manufactured drugs, ICP emission spectrometers to measure the content of inorganic compounds such as lead, and imaging mass microscopes to confirm that drugs are reaching the site of pathogens as designed. Each of these instruments plays a role in verifying drug efficacy and safety rigorously.

Answering the needs of pharma companies and surmounting obstacles to drug development

Automating analysis for more efficient development and quality control

What pharma companies need from Shimadzu is highly reliable analytical results. Even the smallest measurement error can undermine drug efficacy and safety, even leading to health impairment during use.

Shimadzu therefore not only develops and manufactures analytical instruments, but researches analytical methods in collaboration with pharma companies. This is because accurate analysis is not determined solely by the inherent precision of the instrument. Accuracy can also be affected by the way the instrument is operated. As such, Shimadzu also offers support to users in determining the suitability of instruments for specific use cases. This includes the structuring of environments and systems required for accurate instrument operation, as well as preservation and management of operational records.

Furthermore, Shimadzu works with pharma companies to update analytical methods as required to meet increasingly stringent legal restrictions. We also support structuring of data management systems to support smooth regulatory approval of new drugs during the development process. With respect to quality control, Shimadzu backs pharma companies with support for stable quality analysis, helping to ensure that manufacturing defects do not result in shipment stoppages from factories.

In recent years, efficiency is being asked of analytical instruments. In pharmaceutical development, automation is the key to increasing efficiency.

Drug development requires that huge numbers of specimens be analyzed, but analyzing each sample individually is labor-intensive and time-consuming. As such, it is desirable to automate the process.

For example, samples could be left in the instrument at the end of one week, and the analysis would be available when one arrives for work at the beginning of the following week. What pharma companies are looking for is analysis processes that are speedy, reduce human error risk, and deliver more consistent, accurate data, all to the greatest extent possible and without human involvement. Shimadzu has been automating analysis and addressing these challenges through continuing joint research with pharma companies.

Demand for automation in biopharmaceutical (biologic) development is especially strong. Biologics are drawing increasing attention as medicines whose active constituents include proteins produced through recombinant DNA technology and cell culture techniques. This contrasts with conventional, low-molecular-weight drugs manufactured principally through chemical synthesis. Biologics are showing promise in the treatment of diseases where conventional medicines have proven inadequate.

The active constituents in biologicals are very large macromolecules, such as proteins. Moreover, these proteins are extremely complex, making their analysis correspondingly labor-intensive. Biologics are also challenging to manufacture, since numerous impurities can contaminate the product during the lengthy manufacturing process, and identifying these impurities can require a tremendous amount of time. Limits on the human capacity to address such challenges translates to strong demand for automation.

There is also a need to automatically verify cell culture efficiency, search for optimal analysis methods, and analyze the resulting data. By automating labor-intensive analysis, reducing the human resources required, and cutting costs, the cost of biologics to the patient can be restrained.

Creating medicines to cure even hard-to-treat diseases

Pharma companies have presented Shimadzu with successive challenges, such as enhancement of development efficiency through automation. In response, Shimadzu has pushed its analytical technologies forward by meeting these challenges successively. One reason Shimadzu has accumulated its record of problem-solving is that it manufactures and sells products across multiple fields. It is precisely this broad involvement in many fields that has allowed Shimadzu to cultivate broad expertise, and conferred an advantage in generating new concepts from multiple perspectives. For example, ideas for pharma applications may result from addressing challenges relating to environmental or food analysis.

Pharmaceuticals have become progressively more advanced over time, and for diseases that have been previously difficult to treat, ultra-early diagnosis (disease detection prior to the appearance of symptoms) is contributing to the discovery of drugs that can be expected to prevent disease progression.

For example, a drug was recently approved that slows the progression of early-stage Alzheimer's disease by removing disease-causing abnormal proteins in the brain. Furthermore, biomarker measurement has begun to show promise in facilitating early cancer treatment.

In our modern aging society, demand for medicine continues to increase. The challenge is to ensure efficacy and safety, cure previously untreatable diseases, and detect and prevent diseases before symptoms appear. Doing so will not only safeguard human health, but increase the population of those participating actively in society, even in old age. Shimadzu will maintain its collaboration with pharma companies to ensure that everyone can receive appropriate drug treatments without having to forego them for reasons of cost, and to ensure efficacy and safety by supporting efficient drug development and quality control.