セントラル科学 List of Products and Services

Organic matter contained in household and factory wastewater serves as food for aquatic organisms. While BOD and COD represent the amount of oxygen consumed for the decomposition of organic matter, TOC is a water pollution indicator that expresses the absolute amount of carbon contained in organic matter. TOC measurements are conducted across a wide range of industrial fields, from wastewater and environmental water to boiler water, ultra-pure water for semiconductors, and pharmaceutical manufacturing water. There are three series categorized by application fields, each offering three types: lab-type, portable-type, and online-type. ■ M9 Series ... For the pharmaceutical industry (compliant with 3 agencies), features Data Guard function compatible with 21 CFR part 11. ■ M9e Series ... For the semiconductor industry. ■ M5310C Series ... For the water supply sector, with a custom multi-point calibration protocol that complies with notification laws, and capable of meeting the requirements of the "Guidelines for the Validation of Water Quality Testing Methods." *For details, please request materials or view the PDF data available for download.

The bio-burden test is one of the important quality control processes to ensure the safety, quality, and compliance of pharmaceuticals. The culture method requires microbial cultivation, which takes about a week to determine results. The bio-burden rapid analysis device Soleil, developed by Sievers, can detect fewer than 10 viable microorganisms in 100 mL with ultra-high purity in under 45 minutes. It has a strong correlation with the culture method, enhancing the safety of pharmaceuticals and the efficiency of the manufacturing process while minimizing risks. In 2023, the PIC/S GMP Annex 1 was implemented, and rapid methods have begun to be adopted as a means of contamination control. This will be useful for the validation of pharmaceutical water/cleaning/process samples/raw materials/final products.

The endotoxin measurement device Eclipse, developed by Sievers, aims to make endotoxin testing easy for anyone. Many users have experienced challenges with traditional endotoxin measurements, such as the time and effort required for pipetting operations and the occurrence of human errors. Eclipse has achieved semi-automation of endotoxin measurement by developing a dedicated microplate and microfluidic technology. For measuring 21 samples, pipetting operations are reduced to fewer than 30 times, and since the standard samples are pre-filled, the preparation time and effort for testing are significantly reduced. Additionally, the amount of lysate reagent used is reduced by 90% to just 1mL, contributing to the ecological protection of horseshoe crabs. The IQ/OQ can also be completed in just a few days, so you can rest assured.

The online TOC analyzer Sievers M500 is the third generation of online TOC analyzers that has developed Sievers' long-standing reagent-free gas permeable membrane conductivity measurement technology. While inheriting the conventional "accuracy," "reproducibility," and "stability," it has achieved rapid measurement and enhanced data management functions. 【Unique technology compliant with the Japanese Pharmacopoeia】 - Complies with the Japanese Pharmacopoeia General Test Method <2.59 Organic Carbon Test> - Complies with various national pharmacopoeias (USP <643>, EP 2.2.44) - Measures by separating carbon dioxide: gas permeable membrane conductivity measurement method - Calibration using potassium hydrogen phthalate - Detects sodium dodecylbenzenesulfonate with a recovery rate of over 90% 【High performance & high functionality】 - Real-time measurement at 3-minute intervals - Flexible sampling functions - Abundant system protocols - Data integrity compliant with 21 CFR Part 11

The online TOC analyzer Sievers M500e is the third generation of online TOC analyzers that has developed Sievers' long-standing analytical technology in the electronics industry. It adopts Sievers' reagent-free gas-permeable membrane conductivity measurement technology, achieving accuracy, reproducibility, and stability of TOC below 1 ppb. ● Removal of interfering ions using gas-permeable membrane conductivity measurement method ● Significant reduction in running costs due to reagent-free measurement ● Up to 50% reduction in analysis time (compared to the previous model) It is the successor model to the Sievers 500RLe. It enhances accuracy and efficiency, supporting the stable production of ultra-pure water (UPW).

The "Sievers InnovOx Lab Model" is an advanced TOC analyzer that employs the innovative oxidation technology known as "supercritical water oxidation" to decompose organic matter in sample water. It is capable of measuring TOC in samples with high salinity, such as seawater, and in samples containing insoluble substances like cellulose (particle size ≤ 0.8mm). It caters to various applications, including industrial wastewater, sewage, environmental water, and industrial processes. 【Features】 ■ Wide measurement range from 0.05 to 50,000 ppm. ■ Compatible with various applications. ■ Oxidative decomposition of various organic substances. ■ Easy operation with a user-friendly display. ■ Air filter kit that does not require gas. *For more details, please refer to the catalog or feel free to contact us.

This is a support tool from Sievers that is convenient for TOC measurement. It can also be used with TOC analyzers from manufacturers other than Sievers. Cleaning guaranteed vials <Cleanroom Blue TOC Vials 40mL> A set of vials in a blue polypropylene case that can be used in locations where cardboard cannot be brought in. <Cleaning Validation Kit> A set of swabs and vials used for cleaning validation. <Pre-cleaned Vials with Cleaning Guarantee> Allows sampling without worrying about contamination from the container. <40mL Brown TOC Vials> Brown glass vials that prevent sample degradation due to exposure to external light. Other handled vials <40mL TOC Vials (Pre-treated)> Vials for cleaning validation that have been treated with acid to prevent protein adhesion to the glass surface as a pre-treatment. <30mL DUCT Vials> Vials developed to simultaneously collect conductivity and TOC samples with one vial. <Cap & Septa for 40mL Vials> Allows for repeated use of 40mL vials by simply replacing the cap and septa.

This is a set of standard solutions that conforms to the Japanese Pharmacopoeia General Test Method 2.59 for organic carbon testing. It is used for performance evaluation of total organic carbon (TOC) analyzers and comes with a NIST certificate. It can be used with Sievers brand TOC analyzers as well as those from other manufacturers. Since it is pre-prepared, it can be used immediately.

This is a set of standard solutions that comply with USP<643> Total Organic Carbon, accompanied by a NIST certificate. It can be used with Sievers brand TOC analyzers as well as TOC analyzers from other manufacturers. Since it is pre-prepared, it can be used immediately.

TOC is an effective tool for cleaning validation of pharmaceuticals, cosmetics, and medical devices. By using TOC for cleaning validation, improvements in quality, risk reduction, and efficient operations can be achieved. TOC is a simple analytical method that rapidly detects low concentrations of organic compounds and can identify degradation products and contaminants that HPLC cannot detect. Compared to HPLC, which is a specific analytical method that detects only specific components, TOC, being a non-specific analytical method, can comprehensively confirm that excipients, degradation products, and cleaning agents are adequately cleaned. Furthermore, TOC simplifies method development and minimizes equipment downtime, leading to increased efficiency. By using TOC, not only can the cleaning process be evaluated quickly, but it also reduces the workload, maintenance costs, and running costs compared to HPLC.

Sievers TOC vials guarantee the best performance in any test, including pharmaceutical water, cleaning validation, and difficult-to-recover compounds, while minimizing risks. 【Features of Sievers vials】 - Cleaning guarantee - Traceable - Manufactured by a global leader in TOC analyzers - Usable with TOC analyzers other than Sievers - OOS investigation support

The Sievers M9e can accommodate a variety of applications thanks to its unique gas-permeable membrane conductivity measurement method and wide measurement range (0.03 ppb to 50 ppm). The optional turbo mode (analysis time of 4 seconds) is useful for monitoring recovery water. Features of the Sievers M9e: - Matching of measurement deviations - Stability in ultra-low concentration ranges - Automatic operation (calibration / verification / data analysis, etc.) - 12 months of calibration stability - Three models to choose from based on application (laboratory type / portable type / online type) - Sample conductivity measurement function (optional) allows simultaneous measurement of TOC and conductivity - Auto-sampler (optional) can automatically analyze up to 63 samples (40mL each).

- Low concentration stability (quantitative lower limit: 4 ppb) - Operates immediately after power on - No carrier gas required - Calibration frequency is once a year - Short measurement time (4 measurements per sample in 14 minutes) - Compact design - Three types: lab type / portable type / online type - Inorganic carbon removal device (ICR) is built-in as standard - Optional auto-sampler for automatic measurement of up to 63 samples (40 mL vials) - Custom multi-point calibration protocol compliant with notification methods for the water sector

Product lineup according to purpose: Corresponding to each process such as raw water, RO water, reclaimed water, UF/EDI, and use points.

Water quality monitoring using the Sievers TOC analyzer enables equipment maintenance, protection, reduction of downtime, and mitigation of process failures.

- Rapid measurement (initial response 4 minutes, measurement interval 15 seconds *during online measurement) - Simultaneous monitoring of TOC and conductivity - Capable of online/offline analysis with a single unit - Excellent portability suitable for maintenance of pharmaceutical water systems (compact and lightweight) - Compliant with pharmacopoeias of various countries (USP <643>/EP<2.2.44>) - Built-in sample pump allows users to perform calibration and system suitability tests on-site - Standard solutions provided for calibration and system suitability testing - Screen and documentation available in Japanese - Capable of displaying TOC trend graphs

- Rapid measurement (initial response 4 minutes, measurement interval 15 seconds *during online measurement) - Simultaneous monitoring of TOC and conductivity - Capable of online/offline analysis with a single unit - Excellent portability suitable for maintenance of pure water systems (compact and lightweight) - Built-in sample pump allows users to perform calibration on-site - Easy part replacement by users and low maintenance - Calibration standard solution provided - Capable of displaying TOC trend graphs

The Sievers M9 can accommodate a variety of applications due to its unique gas-permeable membrane conductivity measurement method and wide measurement range (0.03 ppb to 50 ppm). Features of the Sievers M9: - No carrier gas required - Stability in ultra-low concentration range - 12 months of calibration stability - Three models to choose from based on application (laboratory type/portable type/online type) - Compliance with data integrity requirements based on 21 CFR Part 11 (optional) - The sample conductivity measurement function allows simultaneous measurement of TOC and conductivity (USP<645> Stage 1) (optional) - An auto-sampler can automatically analyze up to 63 samples (40mL) (optional)

Data integrity is a crucial requirement in pharmaceutical manufacturing, and there is a strong demand to easily manage electronic data and metadata in one place. Pharmaceutical companies must not only ensure patient safety and meet data integrity requirements but also improve production efficiency to respond to production demands. By reviewing data in real-time and conducting trend analysis, processes can be streamlined through encrypted data transfer. Additionally, utilizing electronic signature functionality allows for even faster record reviews. Features of DataShare Elite Software: - Compatibility with both new and old models of Sievers TOC analyzers - Management of metadata including error history and audit trails - Electronic signatures for data (measurement results, audit trails) - Access to lab/online TOC analyzers from a single PC

In cleaning validation, it is important to select the appropriate analytical method according to the purpose. By choosing the optimal analytical method for each phase (design, validation, verification), the risk of product contamination can be minimized.

✓ Rapid measurement of TOC over a wide measurement range Measurement time: 4 seconds Initial response time: 6 minutes (ICR off), 10 minutes (ICR on) Response time: 3.25 minutes Measurement range: 0.20 ppb to 10 ppm ✓ Three models to choose from Lab type / Portable type / Online type ✓ Three measurement modes to choose from Online measurement / Grab measurement / Auto-sampler measurement

The TOC method for cleaning validation is an important technique for evaluating the cleanliness of equipment. The TOC method is recognized as a way to assess the carbon content in samples and is used to evaluate the cleanliness of equipment. In accordance with ICH Q2B guidance, examples of the evaluation of various parameters related to the validation of analytical methods using TOC will be introduced.

TOC allows for the direct measurement of organic matter load. It is preferred over traditional oxygen demand methods like BOD and COD because it does not require hazardous chemicals and results can be obtained in less than 10 minutes.

Pharmaceutical companies are always required to demonstrate validated cleaning programs. Here, we present five ways to successfully implement a cleaning validation program.

In a refinery, strict management of water quality and quantity is necessary for efficient operations. An average refinery consumes about 1.5 barrels of water to produce 1 barrel of crude oil. Rapid decision-making using real-time data contributes to cost and time savings, as well as water reuse and recycling. The water used in refineries varies widely, including cooling water and boiler feedwater, each with different water quality requirements. In particular, boiler feedwater requires high purity. To quickly assess the deterioration of water quality, responsive measuring instruments are necessary. Refineries primarily use large amounts of water for cooling and heating, but significant water is also used in other processes. Water quality monitoring helps facilitate decisions on regeneration/discharge/processes while managing and minimizing water usage and complying with regulatory requirements. Since most of the incoming pollutants originate from natural organic matter, and the main products are organic matter with the primary discharge standards being organic matter concentration, TOC monitoring allows for real-time decision-making and process control improvement. Directly monitoring organic matter throughout the refinery, from river intake to river discharge, aids in operational efficiency, cost management, and plant sustainability.

Cleaning validation is a very important process in the pharmaceutical industry. Various analytical methods are used to ensure that manufacturing equipment is properly cleaned. Among these, TOC analyzers and HPLC are widely used as representative methods. Here, we conducted a cost comparison of TOC analyzers and HPLC from various perspectives (initial costs, maintenance costs, and labor costs).

TOC and conductivity are important analytical items that support cleaning validation, cleaning verification, and cleaning monitoring. TOC measurements can be performed in response to user requests in various settings, including laboratories, manufacturing sites (at-line), and online (final rinse water monitoring from CIP).

- Purpose and Challenges of Cleaning The cleaning process is designed to effectively remove compounds, ensuring that no decomposition products or residual cleaning agents are left in the manufacturing equipment, allowing it to be used for the production of the next batch. Relying on specific analytical methods can take years from design/development/completion and requires significant manpower.

In cleaning validation, when considering worst-case scenarios involving low solubility compounds or poorly designed cleaning processes, TOC analysis is effective. TOC analysis is a non-specific analytical method that can detect substances remaining on surfaces such as APIs, surfactants, and decomposing agents.

- Establishing the Cleaning Validation Process Each process of cleaning validation is unique, and factors such as raw materials, process flow diagrams, work procedures, and minimum batch size (MBS) influence the cleaning process. The cleaning validation process is divided into three stages: design, qualification, and verification, and these should be continuously confirmed and updated throughout the duration of the process. It is necessary to set a Maximum Allowable Carryover (MAC) when switching products in production equipment. The MAC is the amount of the previous product that can be present in the next product without posing a risk to the patient. Here, we will introduce the method for calculating the Maximum Allowable Carryover (MAC) in cleaning validation.

Cleaning validation is an essential process in pharmaceutical manufacturing. However, traditional manual sampling and swab testing are time-consuming, carry a high risk of human error, and are costly. This is where Process Analytical Technology (PAT) comes into play. Based on guidance published by the FDA in 2004, this technology provides recommendations for understanding, controlling, and continuously verifying processes. By using PAT, it becomes possible to understand processes without manual sampling or analysis, leveraging real-time data. Utilizing real-time data on TOC, IC, and conductivity from online TOC analyzers enables comprehensive understanding of the cleaning process through online cleaning validation.

The evaluation of the cleaning process is a very important issue in manufacturing. In particular, to ensure product quality, it is necessary to confirm that the cleaning standards are appropriate. Here, we will introduce a method to evaluate the validity of cleaning standards using the process capability index.

In the pharmaceutical industry, cleaning validation of manufacturing equipment is a crucial element of quality control. In particular, accurately detecting residues of alkaline cleaning agents is essential for ensuring product safety and quality. Here, we will introduce a method for simultaneously measuring the TOC and conductivity of alkaline cleaning agents using the Sievers M9 TOC analyzer. - Characteristics and Importance of Alkaline Cleaning Agents We selected CIP-100Ⓡ as the alkaline cleaning agent commonly used for cleaning manufacturing equipment during product changeovers in the pharmaceutical industry. Its composition includes potassium hydroxide (10-30%) and disodium EDTA (1-5%), which contribute to its cleaning effectiveness. In cleaning validation, it is important to confirm that no cleaning agent remains on the equipment after the final rinse.

Cleaning validation in the pharmaceutical industry is a crucial process to ensure the quality and safety of products. This importance increases significantly when dealing with complex compounds. We will introduce the evaluation of recovery rates of alkaline cleaning agents using Sievers' TOC measurement technology.

The TOC meter Sievers M9 is very effective in quantitatively detecting trace residues of cleaning agents and plays an important role in cleaning validation and process validation. Furthermore, by simultaneously measuring conductivity and TOC, it allows for a deeper understanding of the cleanliness of both ions and organic substances after the cleaning process.

The design of a robust cleaning process for pharmaceutical manufacturing is crucial for cleaning validation. Traditionally, the design of cleaning processes in pharmaceutical manufacturing has focused on reducing the most potent and toxic active pharmaceutical ingredients (APIs). For validated cleaning processes, the emphasis is on reducing risks and demonstrating process control and understanding. A newly highlighted concept for risk reduction is the identification of comprehensive cleanability and master soil. In the past, potential substances were considered individually, and all substances were ranked based on the time required for cleaning completion under worst-case cleaning conditions. The master soil was established based on the time to cleaning completion, and the cleaning process was optimized around the reduction of the master soil. Often, this relied on subjective ranking through visual confirmation as a qualitative indicator. To optimize the cleaning process of pharmaceutical manufacturing facilities, we propose a method to measure total organic carbon (TOC) and conductivity in real-time to evaluate cleanability.

In the pharmaceutical industry, cleaning validation of manufacturing equipment is a crucial element of quality control. In cleaning validation, conductivity is useful for detecting residual cleaning agents, but it cannot accurately assess the concentration of organic substances. TOC is very useful in the cleaning evaluation of manufacturing equipment because it can detect both types of organic substances (conductive and non-conductive). Particularly in cases where non-conductive organic substances are present, relying solely on conductivity for cleaning evaluation increases the risk of missing organic contamination.

Cleaning validation is an essential process to ensure the cleanliness of manufacturing equipment. This process requires highly sensitive and reliable swab or rinse sample analysis. In particular, vials with a low and stable TOC background are necessary. Using kits with high TOC or significant variability increases the risk of errors, leading to incorrect assessments of equipment cleanliness and the possibility of unnecessary cleaning. Sievers' cleaning validation kits provide low TOC backgrounds with minimal variability, resulting in more sensitive and accurate results. Additionally, using vials with a cleaning guarantee ensures the accuracy and completeness of the analysis.

Potassium hydroxide is a commonly used cleaning agent in the pharmaceutical industry. However, it cannot be detected by TOC because it does not contain carbon. Therefore, using conductivity as a detection method is effective. However, there are often trace amounts of residual organic matter, and TOC measurement is essential to detect this. The Sievers M9 TOC analyzer can measure both conductivity and TOC simultaneously, making it useful for detecting residual concentrations of potassium hydroxide.

Sodium hydroxide is a commonly used cleaning agent in the pharmaceutical industry. However, it cannot be detected by TOC because it does not contain carbon. Therefore, using conductivity for detection is effective. However, there are often trace amounts of residual organic matter, and TOC measurement is essential for detecting this. The Sievers M9 TOC analyzer can simultaneously measure both conductivity and TOC, making it useful for detecting residual concentrations of sodium hydroxide.

In the pharmaceutical industry, cleaning validation is an essential element for ensuring the reliability and quality of the manufacturing process. In particular, cleaning validation using TOC is gaining attention for its accuracy and efficiency. Sievers' validation support package for cleaning validation provides a systematic approach to building cleaning validation and complements the existing quality management standards, requirements, and guidelines commonly used in the pharmaceutical and biopharmaceutical industries. This document includes guidance, construction examples, worksheets, templates, and sample protocols, significantly reducing the time and effort required to establish cleaning validation.

In recent years, the demand for gluten-free products has surged. Consequently, in food and beverage factories, the cleaning of manufacturing equipment has become an increasingly important issue when producing both gluten-containing and gluten-free products. In particular, strict cleaning between batches is required to prevent carryover of materials between products. - Challenges in Gluten-Free Management When dedicated equipment for gluten-free products cannot be secured, it is necessary to thoroughly clean the manufacturing equipment. Allergen testing is mandated to prove that no specified ingredients remain after cleaning, but this requires time and skilled techniques. Traditional testing methods, such as the ELISA method, have high accuracy but are labor-intensive and time-consuming, leading to a demand for more efficient methods. Against this backdrop, the Sievers M9 TOC analyzer is gaining attention. This instrument can simultaneously measure TOC and conductivity, making it very effective for determining the nature of contaminants remaining after equipment cleaning.

In the food and beverage industry, effective cleaning of manufacturing equipment is essential to deliver high-quality and safe products to consumers. It is particularly important to appropriately reduce the risk of contamination by microorganisms. According to the FDA, the primary cause of product recalls in the food and beverage industry in 2017 was product contamination by microorganisms. Therefore, proper cleaning processes are required to reduce microbial contamination. Additionally, it is important to have means to verify the effectiveness of the cleaning process. TOC (Total Organic Carbon) is a widely adopted non-specific analytical method for detecting potential contaminants such as product residues, detergents, and microorganisms. To use TOC, it is necessary to consider the recovery rates and linearity of substances that may remain after cleaning. While testing for chemical contaminants and compounds using TOC is common, there is limited information regarding the recovery rates of microorganisms. By using the Sievers M9 TOC analyzer, it is possible to detect microbial residues at lower concentrations than visual inspection in cleaning evaluations. TOC analysis is effective for measuring residues, monitoring cleaning processes, and reducing overall risks. This enables more accurate and efficient microbial management in the cleaning evaluation of manufacturing equipment.

In the pharmaceutical and cosmetics industries, cleaning validation of manufacturing equipment is a very important process. In particular, accurately detecting residues of insoluble and difficult-to-decompose compounds is essential for ensuring product quality and safety. TOC analyzers are widely adopted non-specific analytical methods for detecting residual products and cleaning agents in manufacturing equipment. The Sievers M9 TOC analyzer can measure with high accuracy even for insoluble and difficult-to-decompose compounds, providing reliable data.

In the pharmaceutical industry, cleaning validation is an essential process to ensure the quality and safety of products. In particular, accurately detecting residues of protein samples is crucial for guaranteeing the cleanliness of manufacturing equipment. TOC analyzers consist of a combination of oxidation methods and detection methods. - Oxidation Method of TOC Analyzers Commercially available TOC analyzers oxidize organic compounds to carbon dioxide using methods such as combustion oxidation or oxidants combined with ultraviolet oxidation. - Detection Method of TOC Analyzers To detect the concentration of carbon dioxide generated from the oxidation of organic compounds, non-dispersive infrared absorption (NDIR) methods and conductivity methods are commonly used. - Sievers Measurement Technology Sievers TOC analyzers employ a wet ultraviolet oxidation combined with gas-permeable membrane conductivity measurement method, allowing for high accuracy in measuring recovery rates even for protein samples, thus providing reliable data. This is expected to ensure product quality and safety and contribute to the overall reliability improvement in the industry.