Significance and Use
Pharmaceutical water is the most common component or ingredient used in pharmaceutical and biopharmaceutical manufacturing. Acceptable purity of the water is important to the quality of the final pharmaceutical product. TOC concentration is a key indicator and attribute of the purity of this water and also an important monitor of the overall performance of the water purification system. TOC analysis is the measurement of all the covalently bound carbon present in the water, not including carbon in the form of carbon dioxide (CO2), bicarbonate icon (HCO3–), or carbonate ion (CO32–), and is reported as the mass of organic carbon per volume.
Application of this practice provides pertinent information to make informed decisions on the release of water meeting pharmaceutical TOC concentration specifications.
1.1 This practice establishes an approach to the real-time release testing (RTRT) of pharmaceutical water based on the total organic carbon (TOC) attribute using on-line total organic carbon (OLTOC) instrumentation that is in agreement with current regulatory thinking.
1.2 This practice is harmonized with or supports the concepts of relevant ASTM International Committee E55 on Manufacture of Pharmaceutical Products standards, ICH Harmonized Tripartite Guidelines, the US FDA PAT Guidance, and US FDA Pharmaceutical cGMPs.
1.3 This practice does not provide general guidance information for pharmaceutical procedures that are considered standard practice in the pharmaceutical industry. This practice provides specific guidance for non-standardized procedures.
1.4 This practice does not address the user’s various internal procedures for risk, change, or quality management systems. The overall project effort associated with this practice shall be proportional to the overall risk of failing the pharmaceutical water’s TOC concentration specification.
1.5 This practice does not purport to establish how to comply with pharmacopeias. The RTRT methodology selected must assure compliance with the user’s current required pharmacopeias. However, compliance with pharmacopeia TOC methods is not necessarily sufficient to meet current regulatory expectations for RTRT.
1.6 This practice does not purport to substitute for or replace compendial bioburden testing requirements. It is strictly applicable to the TOC attribute of water quality.
1.7 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.
2. Referenced Documents (purchase separately) The documents listed below are referenced within the subject standard but are not provided as part of the standard.
D4839 Test Method for Total Carbon and Organic Carbon in Water by Ultraviolet, or Persulfate Oxidation, or Both, and Infrared Detection
D5173 Test Method for On-Line Monitoring of Carbon Compounds in Water by Chemical Oxidation, by UV Light Oxidation, by Both, or by High Temperature Combustion Followed by Gas Phase NDIR or by Electrolytic Conductivity
D5904 Test Method for Total Carbon, Inorganic Carbon, and Organic Carbon in Water by Ultraviolet, Persulfate Oxidation, and Membrane Conductivity Detection
D5997 Test Method for On-Line Monitoring of Total Carbon, Inorganic Carbon in Water by Ultraviolet, Persulfate Oxidation, and Membrane Conductivity Detection
D6317 Test Method for Low Level Determination of Total Carbon, Inorganic Carbon and Organic Carbon in Water by Ultraviolet, Persulfate Oxidation, and Membrane Conductivity Detection
E2281 Practice for Process and Measurement Capability Indices
E2363 Terminology Relating to Process Analytical Technology in the Pharmaceutical Industry
E2500 Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment
E2537 Guide for Application of Continuous Quality Verification to Pharmaceutical and Biopharmaceutical Manufacturing
ICS Number Code 11.120.10 (Medicaments); 13.060.50 (Examination of water for chemical substances)
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