Qualified Services Quality without Limits

2-SERVIZIO A DOMICILIO Oltre al servizio presso la Vs sede, per la strumentazione che necessita di controlli specifici presso i Ns laboratori è possibile usufruire del servizio a domicilio che prevede:Disinstallazione dello strumento, Taratura dello strumento presso la ns Sede, rinstallazione dello strumento con verifiche documentata di funzionamento. Details...

5- NUOVI SERVIZI •Ricertificazione Cappe da laboratorio chimico e microbiologico (Biohazard, chimico, minienviroment).•Ricertificazione linee di distribuzione Ultrapure Facilities (DIW acqua, UPG gas, UPC chemical, Semiconduttori) •Supporto in processi di investigazione per la determinazione della contaminazione in loop di acque e Facility pure ed ultrapure ( UPW , PW )•Analisi su prodotti intermedi e finiti di : TOC, determinazione della concentrazione di particelle nei liquidi, conducibilità, ph•Risk Analysis •Supporto/ readazione documentazione di progetto e convalida ( URS, IOPQ, FS, HS, SWS, VPL/VMP, FINALY REPORT, SOPs, LAY OUT , P&ID)•Risk based approach su sistemi di monitoraggio parametri ambientali e di processo Details...

7-DOMANDE E RISPOSTE Total Organic Carbon per USP24 On May 15, 1998, the United States Pharmacopeial (USP) Convention implemented changes to the long-standing watermonographs. These changes require modifications to the water quality attributes and how the parameters are monitored. Mostnotable was the inclusion of Total Organic Carbon (TOC) analysis and the deletion of the oxidizable substance test.There are a number of issues pertaining to implementation of the new tests that have not been addressed. For example, TOC is alimit test and the limit must be updated "periodically". This is a simple requirement for single analyzer systems, however,manufacturers using several instruments may have several limits on the same water system. The standards used require carefulhandling, storage and additional documentation. The conductivity cell and meter have two separate calibration requirements andthe acceptable method for conducting these calibrations is not completely clear.Fully implemented in early 2000, USP 24 includes some modifications to USP 23 monographs. Relevant to TOC andconductivity testing chapters <643> and <645>, the only change made was in the drying of sucrose for standards preparation(sucrose drying time was changed from two hours at 105º in USP 23, to three hours at 105º in USP 24). No other changes impacttesting procedures from USP 23.In this document, Ionics Instruments offers important responses to questions you may have when implementing testing forChapters <643> and <645> of the water monographs.How often must I perform System Suitability for my TOC analyzer?Unfortunately, the absolute answer to this question is, periodically. Therefore, it is each user's responsibility to define periodically.Here are some ideas that can help you define “periodically” in a useful way.When asked about this term, "periodically", members of the PhRMA Water Quality Workgroup who crafted the language for theUSP 24 chapter <643> said, "frequently to begin with so you can determine the most appropriate frequency for your facility."Ionics Instruments does not recommend a specific time period to correlate to the term periodically. The following paragraphsshould help you assign a definition to the term periodically.System suitability is a quality assurance measure to demonstrate and document acceptable analyzer performance. If the suitabilityof the analyzer is demonstrated to be acceptable both before and after the water testing, the results are recognized as acceptable. Atypical scenario might be that an initial suitability test is determined to be acceptable and the water is released for use in product. Ifa second suitability test fails the USP criteria, all the water tested after the initial suitability determination will be suspect. The result is an internal investigation on the impact the water may have had on the product.In most quality control laboratories we have visited, system suitability is measured daily with every batch of samples. In this way,if suitability fails, corrective action is taken minimizing the impact on manufactured product. On the other end of the spectrum,many water system engineers who are familiar with this level of data scrutiny assume that quarterly testing is sufficient. In theevent that a once per quarter test fails, all of the water that went into product during the quarter would be suspect.How often you conduct system suitability testing is a matter of risk. Daily suitability testing eliminates risk,but increases work. Testing infrequently decreases the amount of work required, but increases risk of a costly internalinvestigation. Ionics Instruments on-line and laboratory TOC analyzers allow system suitability to be performed in less than twohours. Our patented technology allows you to pick any frequency of conducting system suitability that you feel is necessary toreduce risk for your organization.Q&A Implementing Total Organic Carbon Testing for USP 241Must System Suitability be performed for every TOC analyzer I have?Yes, suitability must be demonstrated for every analyzer used to make decisions regarding Purified Water or Water for Injection.With every system suitability test you perform, a "limit response" is established. To pass the USP TOC limit, your water musthave a TOC value below the limit response. Therefore, each TOC analyzer that passes suitability will also have a unique limitresponse. If you are considering putting several TOC analyzers on-line, call Ionics Instruments representatives. We can share withyou what others are doing to solve this problem.May I return my analyzer to the manufacturer for suitability determination?Absolutely not! The test must be performed on-site. The suitability determination should reflect your lab’s individual performancecapabilities. This is why Ionics Instruments has made system suitability determination so easy. If you have been told you can sendan instrument back to the factory for suitability determination, you have been mislead.Can the Suitability standards be used for analyzer calibration as well as the suitability test?The USP sucrose and 1,4-benzoquinone specified in Chapter <643> are for suitability purposes only. It is advisable to follow themanufacturers’ recommendations for calibration, which may require different reference materials. This is suggested in Chapter<643> where the USP states, "Prepare appropriate reagent blank solutions or other specified solutions needed for establishing theapparatus baseline or for calibration adjustments following the manufacturers’ instructions."USP 24 Chapter <643> says I must use a calibrated analyzer. Does this pertain to online as well as laboratory TOC analyzers?Yes, although the mechanism of calibration is not specified. It is important to perform system suitabilities and calibrationverifications periodically on both on-line process instrumentation just as with laboratory equipment.If my USP water fails chapter <645> conductivity specifications with my on-lineinstrumentation, what can I do?There are three testing stages outlined in USP 24 for monitoring conductivity compliance according to Chapter <645>. Only inthe event of failure at all three stages is the sample judged to be out of compliance. CO2 ingress is the most common cause ofhigh conductivity in on-line USP water systems, and can come from a variety of sources (R/O systems, storage tanks exposed tothe atmosphere, etc.). Failing Stage 1 specifications of Chapter <645> is not really that uncommon, and testing in accordancewith Stage 2 procedures often elucidates the extraneous conductivity to be the result of dissolved CO2 in the water system. UponStage 2 testing, most samples failing Stage 1 specifications are found to be in compliance with USP <645>, and released.Failing Stage 2 specifications (and certainly those of Stage 3) often indicates issues with water systems themselves. Resindegradation and leaching of ions from poorly passivated or deteriorating metal components are two common examples. The firstresponse to failing a USP conductivity test should be a thorough examination of your water system.I have heard that 1,4-benzoquinone is light sensitive. Is there a problem with long term storage of this material?Ionics Instruments has conducted extensive research on 1,4-benzoquinone, and we have confirmed that this compound isextremely light sensitive. 1,4-Benzoquinone changes immediately when added to water. You can witness this by placing solutionin the open laboratory for several hours. The yellow stock solution will eventually turn to dark brown. If you prepare 1,4- benzoquinone in your laboratory, always prepare the solutions for immediate use.It is important to recognize that although 1,4-benzoquinone does undergo changes, this change does not impact the actual carboncontent of the solution. Some TOC analyzers will give erroneous TOC values from 1,4-benzoquinone solutions that have not beenstored properly.I am worried about contaminating samples for off-line TOC analysis. Is on-line TOC a better option to avoid this problem?Yes. On-line analyzers are generally free from the sample contamination issues that can impact off-line or laboratory typeanalyzers and thus, typically provide a higher degree of accuracy. Off-line TOC samples, however, can be measured withminimum contamination using validated protocols and proper training.It is important to understand that if you are performing both on-line and off-line TOC tests in your facility, the results will notmatch exactly. This is due to low level "contamination" that can be introduced in handling container storage and sample portexposure. The impacts are measurable, but will not impact the quality of data. That is why the USP allows either on-line or offlinetesting. If you have questions about on-line to off-line data, call Ionics Instruments. Our technical experts can discuss thiswith you.Is the pharmaceutical industry trending toward on-line or off-line TOC analysis?The companies we have communication with are opting for laboratory analysis initially, while they begin to validate their watersystems. Later, they plan transition to on-line testing to reduce the labor costs associated with taking samples to the lab.Other companies have the full intention to move to on-line analysis quickly. These companies are generally more familiar with thebenefits of measuring on-line in a continuous manner as a water system process control parameter. Remember, either approach isacceptable, the most important thing is that you gather all the facts and plan your implementation strategy with all the necessaryprincipals involved. Typically, this will include the facilities, purchasing, and quality assurance persons responsible forimplementing this new USP requirement.Once you have put your information team together, use this booklet as a place to begin. Answer all these questions for yourfacility and you will be off to an excellent start.How much do TOC analyzers cost?TOC analyzers range in price from $10,000 to $40,000 (USD). When determining which TOC analyzer to purchase, werecommend you also consider the analyzer operating costs. In some cases, these costs exceed the capital cost of the analyzerwithin the first year.Another important cost to consider is the cost of water to waste. Analyzer operating volumes vary from 20 - 500 m./min and allthat water goes to waste.I have been doing cleaning validation using TOC for several years, can I use the same analyzer for EP Purified Water testing as well?The answer is maybe. Some TOC analyzers were originally developed for higher level TOC samples [TOC>0.5 ppm]. Theseanalyzers will not have sufficient low level detection capability to test clean Purified Water or Water for Injection. Similarly,analyzers can be designed specifically for low-level purified water and may lack the capacity to analyzer cleaning validationsample. Before you decide to use existing equipment, evaluate the analyzer’s detection limit and make certain you have sufficientsensitivity to conduct water testing.Chapter <643> says that glassware must be "scrupulously" clean. What does that mean?All glassware contributes some level of TOC to your samples. This can range from <10 mg/L (ppb) to much higher levels.Glassware for TOC testing can either be cleaned using appropriate protocols, or purchased precleaned. Low level TOC glasswarecan be purchased from Eagle Picher, Miami, OK (1-800-331-7425). We have found this glassware to be exceptionally low inbackground TOC. More information on glassware cleaning procedures is available from Ionics Instruments.Can TOC analyzers detect endotoxins?There is no evidence that TOC analyzers are capable of providing information regarding endotoxins in pharmaceutical watersystems. This is not to say that TOC analyzers do not detect the carbon contained in the endotoxins. Endotoxin levels are so low,relative to the background TOC levels in the water, that it is very difficult to attribute TOC changes to changes in endotoxin levels.My on-line TOC analyzer seems to "spike" above the limit response. What do I need to do with this data?Any TOC result that is above the limit response should be investigated. This may mean evaluating the analyzer to ensure that it wasworking properly, correlating the data to other water system events (change out of resins, maintenance on the system, etc.), anddocumenting the findings.I am using a laboratory TOC analyzer to release my water and I have a couple of online trend TOC analyzers that I can not validate but I use them to identify potentialproblems with my water system. Is this acceptable?This is a very gray area as far as enforcement is concerned. The most conservative answer is that any analytical instrument thatprovides data must be validated. If you do not validate the analyzer, it will be your responsibility to demonstrate to the FDAInspector that it truly is for information and no action will be taken based upon the analyzer’s response. Details...