The role of TOC validation technology in the pharmaceutical industry
author: Otis
2022-12-03
Drug production requires strict quality control and accurate analysis and testing methods. The US Pharmacopoeia (USP), the European Pharmacopoeia (EP) and the Japanese Pharmacopoeia (JP) have used TOC analysis as proven clean validation, purified water (PW) and intravenous water (WFI).
TOC analysis is an indirect method used to ensure the cleanliness of the water for drug production and the production equipment for producing drugs. TOC is a "comprehensive" cleaning verification procedure for the main manufacture of contaminants because the presence of carbon indicates various cross-contamination, including cleaners, foreign bodies (paint, hair, building materials, etc.) and bacteria.
Validation required by the pharmaceutical industry
Cleaning Verification-Cleaning Verification Program Verification Using in-place cleaning procedures The cleaned pharmaceutical and cosmetic manufacturing equipment are not contaminated before starting the next production run. Pollution may reduce the safety, strength, quality, or purity of the product.
PW and WFI validation-WFI is the water used to manufacture the injectable drugs. Both PW and WFI are essential for drug preparation and must be within the ppb, or even the sub-ppb, carbon range.
The Verification Technology in the Pharmaceutical Industry
The pharmaceutical industry uses several common validation techniques, including:
Thin-layer chromatography method (TLC)
High-pressure liquid chromatography (HPLC)
spectrophotography
conductivity
Total organic carbon (TOC)
HPLC / TLC
Although HPLC can be very accurate and quantitative, it is often highly selective in its methods because each target compound interacts with the column differently, depending on the polarity, aperture, and stationary phase. Therefore, HPLC / TCL is very useful for identifying known selective compounds, but it cannot identify other types of contamination (foreign bodies and bacteria) that analysts may not be aware of. Furthermore, TLC is not quantitative and the amount of contamination cannot be determined. Finally, HPLC analysis requires superior operator skills to develop analytical methods. On the other hand, TOC analysis, quite the opposite, requires minimal operator skills to achieve successful results.
Spectrophotometer
The spectrophotometer was resolved in a closed glass chamber, where the carbon dioxide was oxidized using the persulfate oxidation method. The CO 2 is dispersed into the solution, which becomes carbonic acid and indicates the presence of the carbon by changing the color. This color change is directly proportional to the carbon concentration in the sample. Since the spectrophotometric analysis measures the color change of the reactive compounds, it itself has many interfering factors, including sulfur, chlorine, manganese, calcium, copper, and iron, resulting in unreliable results.
Conductivity
Conductivity measures the conductivity of the sample before and after oxidation; this difference yields the amount of TOC. Samples in the oxidative phase form a dissolved CO2, It acts as a weak acid, enhancing the electrical conductivity of the sample. The size of the conductivity is directly proportional to the number of TOC in the sample. Hydrophobic gas permeable membrane is used to improve the accuracy of conductivity methods to enable dissolved CO2Greater discrimination than the other compounds.
Total organic carbon (TOC)
The TOC methods can employ one of two different oxidation techniques:
The UV-persulfate oxidation method
High-temperature catalytic oxidation method
UV persulfate oxidation: Transfer sample aliquots to a UV reactor, in which oxidation is achieved by a combination of a chemical oxidant (usually sodium persulfate) and UV light. Carbon oxide in the sample is converted into carbon dioxide and swept over by a detector using conventional non-dispersive infrared (NDIR) detection.
High-temperature catalytic oxidation method: Use a catalyst to help burn organic carbon into CO2. In these systems, furnace closed catalyst tubes with samples are heated to 680℃ -1000℃ to oxidize carbon to CO through a combination of temperature, oxygen-rich environment (usually super-zero air or oxygen-carrying gas)2And catalyst. Then the CO2Scan to the NDIR detector.
Since the catalysts used in the catalytic combustion system may have carbon artifacts producing a carbon background, using the UVP system for the low-concentration analysis required for PW and WFI applications is recommended. The only major interference in the NDIR assays used in both systems was the halogen and sulfur. To mitigate their effects, most TOC systems include a halogen washer and provide an alternative sulfur washer.
In conclusion, the TOC analysis method stands out among the numerous assays. An excellent approach from all aspects of the performance. Optosky's TOC analyzer TOC-2000 and TOC-3000 simply use the above TOC analysis method, which is very suitable for use in pharmaceuticals, and we are very welcome to consult for details.
TOC analysis is an indirect method used to ensure the cleanliness of the water for drug production and the production equipment for producing drugs. TOC is a "comprehensive" cleaning verification procedure for the main manufacture of contaminants because the presence of carbon indicates various cross-contamination, including cleaners, foreign bodies (paint, hair, building materials, etc.) and bacteria.
Validation required by the pharmaceutical industry
Cleaning Verification-Cleaning Verification Program Verification Using in-place cleaning procedures The cleaned pharmaceutical and cosmetic manufacturing equipment are not contaminated before starting the next production run. Pollution may reduce the safety, strength, quality, or purity of the product.
PW and WFI validation-WFI is the water used to manufacture the injectable drugs. Both PW and WFI are essential for drug preparation and must be within the ppb, or even the sub-ppb, carbon range.
The Verification Technology in the Pharmaceutical Industry
The pharmaceutical industry uses several common validation techniques, including:
Thin-layer chromatography method (TLC)
High-pressure liquid chromatography (HPLC)
spectrophotography
conductivity
Total organic carbon (TOC)
HPLC / TLC
Although HPLC can be very accurate and quantitative, it is often highly selective in its methods because each target compound interacts with the column differently, depending on the polarity, aperture, and stationary phase. Therefore, HPLC / TCL is very useful for identifying known selective compounds, but it cannot identify other types of contamination (foreign bodies and bacteria) that analysts may not be aware of. Furthermore, TLC is not quantitative and the amount of contamination cannot be determined. Finally, HPLC analysis requires superior operator skills to develop analytical methods. On the other hand, TOC analysis, quite the opposite, requires minimal operator skills to achieve successful results.
Spectrophotometer
The spectrophotometer was resolved in a closed glass chamber, where the carbon dioxide was oxidized using the persulfate oxidation method. The CO 2 is dispersed into the solution, which becomes carbonic acid and indicates the presence of the carbon by changing the color. This color change is directly proportional to the carbon concentration in the sample. Since the spectrophotometric analysis measures the color change of the reactive compounds, it itself has many interfering factors, including sulfur, chlorine, manganese, calcium, copper, and iron, resulting in unreliable results.
Conductivity
Conductivity measures the conductivity of the sample before and after oxidation; this difference yields the amount of TOC. Samples in the oxidative phase form a dissolved CO2, It acts as a weak acid, enhancing the electrical conductivity of the sample. The size of the conductivity is directly proportional to the number of TOC in the sample. Hydrophobic gas permeable membrane is used to improve the accuracy of conductivity methods to enable dissolved CO2Greater discrimination than the other compounds.
Total organic carbon (TOC)
The TOC methods can employ one of two different oxidation techniques:
The UV-persulfate oxidation method
High-temperature catalytic oxidation method
UV persulfate oxidation: Transfer sample aliquots to a UV reactor, in which oxidation is achieved by a combination of a chemical oxidant (usually sodium persulfate) and UV light. Carbon oxide in the sample is converted into carbon dioxide and swept over by a detector using conventional non-dispersive infrared (NDIR) detection.
High-temperature catalytic oxidation method: Use a catalyst to help burn organic carbon into CO2. In these systems, furnace closed catalyst tubes with samples are heated to 680℃ -1000℃ to oxidize carbon to CO through a combination of temperature, oxygen-rich environment (usually super-zero air or oxygen-carrying gas)2And catalyst. Then the CO2Scan to the NDIR detector.
Since the catalysts used in the catalytic combustion system may have carbon artifacts producing a carbon background, using the UVP system for the low-concentration analysis required for PW and WFI applications is recommended. The only major interference in the NDIR assays used in both systems was the halogen and sulfur. To mitigate their effects, most TOC systems include a halogen washer and provide an alternative sulfur washer.
| Comparison of drug validation techniques | |||||
| method | Residual drugs | cleaner | Accessories 1PW | byproduct | germ |
| thin layer chromatography | yes | fault | fault | fault | fault |
| high pressure liquid chromatography | yes | yes | fault | fault | fault |
| spectrophotography | yes | fault | yes | fault | fault |
| conductivity | yes | yes | yes | yes | fault |
| total organic carbon | yes | yes | yes | yes | yes |
| Accessient 1: an inactive substance as a carrier or medium of drugs or other active substances. | |||||
In conclusion, the TOC analysis method stands out among the numerous assays. An excellent approach from all aspects of the performance. Optosky's TOC analyzer TOC-2000 and TOC-3000 simply use the above TOC analysis method, which is very suitable for use in pharmaceuticals, and we are very welcome to consult for details.
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