Version 3 Application Notes

Transcription

1 Integrated Solutions Version 3 Application Notes Tablet Dissolution, Content Uniformity and Sample Preparation Automation unique automated analytical solutions for both UV and HPLC Analysis

2 The IDISis is a unique system for customers to configure analysis for Dissolution, Content Uniformity, Sample Preparation and Measurement of Liquid Finished Products. The results for each application are calculated in real time and are available anywhere on the company s network that has an IDISis client installed. IDISis automate experiments more easily and with a higher level of integration than with other instruments thus allowing you to gain greater productivity, deliver analysis results in faster times with reduction in labour costs. One software for multiple applications will also greatly reduce training time and costs and provide quicker turnaround times in application method development and in Quality Control. You can realise the return on your investment with IDISis data management using the power of Oracle 10g database. Applications are configured under the security and compliance stipulated for 21 CFR part 11 with functionality over and above that of our competitors. From setting user access to configuration for electronic signing, this seamless integration allows the system administrator to easily manage compliance issues for day-to-day analysis. Page 2 of 28

3 One Software Solution IDISis automate UV and HPLC analysis to reduce labour costs and increase productivity with Oracle Database for data integrity For the first time ever, one software for both UV and HPLC analyses with automation for ph and profiling of ph in each Vessel throughout the analysis. This unique system also provides unparalleled performance for Sample Preparation and measurement with the ASP2000 Analytical Processing Workstation.! The most comprehensive dissolution and Content Uniformity measurement software available today! Meeting the quality standards and Validation requirements of the pharmacy industry! Choice of different spectrophotometers! Online analysis with Agilent Chemstation and Waters Empower! Oracle database storage for data integrity, security and scalability! Network database management for data centralisation and availability Page 3 of 28

4 IDISis support for different USP Apparatus types IDISis Design Functionality! Automation of most Dissolution Tests for USP apparatus 1, 2, 3, 4 and 7! Utilises many different makes of Dissolution Baths and Spectrophotometers! Manual Data Input from the keyboard for UV or HPLC processing and reporting! Integrates with HPLC CDS from Agilent and Waters! F1 and F2, Similarity and Difference calculations! Regulatory Compliance to 21 CFR Part 11 with Electronic Signing! Easily manipulated Report Organiser! Automated and configurable Data export to LIMS! Real time Networking of data stations Page 4 of 28

5 IDISis can run multiple dissimilar analyses from one workstation. Driver Linkage with Unique Solution Path Technology! Support for a wide range of Baths, Spectrophotometers, Pumps, Samplers and HPLC CDS.! Unique Solution Path Technology - configuration for different analysis that requires no additional reprogramming. - support for Closed and Open Loop Dissolution systems. - automate testing for USP apparatus 1,2, 3 and 4. - We provide automation for UV or HPLC analysis. - collect and store samples in ASP2000 Analytical Processing Workstation to perform online dilution, mixing and injection into UV or into HPLC. - Online analysis or Offline analysis for liquid Sample Preparation and Measurement Page 5 of 28

6 Application Note 1 - Closed Loop Dissolution Testing The IDISis system can control most types of dissolution Baths, Pumps and Spectrophotometers to allow users to configure Closed Loop dissolution systems. The IDISis methodology is far in advance of any other dissolution system and allows for fixed or wavelength scanning, MultiComponent analysis with unlimited Sampling Intervals and Sample Grouping with individual group statistics for product comparison. IDISis is the only dissolution system to allow the user to create and automate multiple ph and Media change with online calculations for each Media. Results, which comprise Absorbance, %Dissolution, Temperature, Speed or ph etc., are displayed numerically and graphically in real time as the experiment proceeds. During the experiment, results for each sample measured are stored in the Oracle Database thus protecting data already acquired in case of power failure Demo Bath Icalis PCP490 Spectrophotometer IDISis can also run Multiple Dissolution experiments using one spectrophotometer that has cell changer having 14 or more Cell positions. Page 6 of 28

7 Application Note 2 Multiple Dissolution Baths using one spectrophotometer IDISis enables users to configure systems so that multiple Baths can use 1 spectrophotometer. With this configuration, each vessel from a Bath is selected in turn by a Sampling Valve and is read after pumping. These systems are applicable to Dissolution analyses that require limited or long sampling intervals. The IDISis automation lends itself perfectly to this application by allowing multiple experiments to be performed from one workstation. Each experiment can be a different product and can start and finish at different times Valve 1 VS1 Spectrophotometer Cavro XL3000 Waste Vessel Dissolution Bath Page 7 of 28

8 Application Note 3 Manually read or input by hand raw data (Blanks, Standards and Samples) from UV or HPLC analysis IDISis provides configuration for users to input raw data from experiments. Data can be read form a spectrophotometer etc, or input by hand or read from a text file. DISis will then process and mange the results as though they were collected from an DISis automated experiment. Very simple experimental configuration Configuration is very simple but flexible enough to allow for Sample Loss. Any combination of Blank, Standards and Samples can be measured. Data input can be for UV or Fluorescence or for HPLC Area / Height. Spectrophotometer Data input appears as for normal measurement Dissolution profile for Manual Data Input appears exactly as for normal IDIS experiments. Page 8 of 28

9 Application Note 4 - Dilution and UV Measurement of Dissolution Samples utilising ALS ASP2000 Analytical Processing Workstation When samples are to be Collected, Diluted and Measured, IDISis can be configured to automate this very labour intensive task and deliver results in real time faster and more reliably than manual operations. Thus greatly improving productivity. Simply start the analysis, drop the tablet and our automated system will perform the rest including measuring Standards and Blanks. A unique Deferred Data Collection thread ensures that samples are always collected at the correct times while optimising the system to process the samples (Dilution and Injection), then measure and report the results Cavro XL3000 P3 Demo Bath 1 D ASP2 000 I C A L I S Spectrophotometer GP2 Icalis ASP2000 Autosampler ASP01006 Icalis PCP Page 9 of 28

10 Application Note 5 Collection, Dilution, and HPLC Measurement of Dissolution Samples using ASP2000 Analytical Processing Workstation with Chemstation or Empower When samples are to be Collected, Diluted and Measured for HPLC analysis, IDISis is the first dissolution software to provide two-way communication with Agilent Chemstation and Waters Empower utilising most makes of Dissolution Baths. From dropping the tablet, this automated system will perform all the sequences including measuring Standards and Blanks. A filter unit can be incorporated to provide filtration down to 0.45µ.! Sample Set is automatically created by IDISis.! Dilution and mixing prior to injection with options to add a reagent to stabilise the molecule.! Real time HPLC Dissolution profile (graphic and numeric) for %Dissolution and Area / Height Values.! Meta data such as Temperature, Speed and ph collected and plotted throughout the experiment.! Reprocessing and Sample Re-measurement.! Optional automated ph Change, monitoring and profiling in each Vessel! An open system, for easy visualisation of operation, accessible for basic maintenance Icalis ASP2000 HPLC Injection Valve ASP01023 Cavro XL3000 C1 Demo Bath 1 D1 ASP2 000 Agilent ChemStation I C A LI S Cavro XL Syringe Diluter C Icalis ASP2000 Autosampler ASP01023 Page 10 of 28

11 Sample Set / Sequence Table created automatically by IDISis IDISis automatically creates the sequence for the HPLC CDS, alleviating the user from this onerous task ultimately saving valuable time. IDIS Blank, Standard and Sample names are transferred to the HPLC CDS for each interval. Page 11 of 28

12 Application Note 6 - ph Change by Media Removal and Addition with optional ph Monitoring in each Vessel Whether analysis is for UV or HPLC detection, IDISis provide the most advanced functionality for changing the ph throughout the experiment. Systems for Discrete or Gradient Media Addition can be configured with Media removal to allow for a single or multiple Media Change during the analysis, results calculated and displayed in real time. When measuring using UV detection, Standards can be read for each Media using different wavelengths and extinction coefficient values are calculated for each media. There is no need to change the method or the Bath Metrohm 780 ph Meter CAT Pump MD Dissolution Bath Icalis PCP490 PCP Spectrophotometer Valve Page 12 of 28

13 Application Note 7 Content Uniformity Measurement - for Solid or Liquid Finished products Whether by UV or HPLC analysis, ASP2000 Analytical Processing Workstation will allow the users to configure Dilution, Mixing, Injection and Measurement of Samples in liquid form for Solid and Liquid Finished products. This application can be used with a UV or HPLC Chromatography Data System attached or the ASP2000 Analytical Processing Workstation can be used to dilute and mix to prepare samples for further analysis. In practice, Samples in liquid form are loaded onto the ASP2000 Automated Workstation and placed in racks. These samples can be Diluted, Mixed or treated with a Reagent to enhance detection or to stabilise the active component, mixed then measured using a Spectrophotometer or HPLC. The system can also be configured to prepare multiple Standards of different concentrations by dilution from a Standard stock solution. Single Syringe Dilutor 1 CU 1 AS P2 000 IC A L I S Spectrophotometer D2 Icalis ASP2000 Autosampler ASP01006 Multiple Samples can be defined Any number of Blanks or Standards can also be configured. Page 13 of 28

14 Multiple procedures can be defined and used to process Groups of samples and or individual Standards and Blanks Samples can be bracketed using any combination of Standards and Blanks as shown here. A Combination of about 250 Samples, Standards and Blanks can be analysed for Dissolution or for Content Uniformity determination. Batch Processing The ASP2000 Analytical Processing Workstation can be configured to perform Batch Processing. Multiple Batches of different products can be placed on the Workstation and with the aid of the ALS VS601 Valve; different Diluent media can be configured for each method. Page 14 of 28

15 Results for Content Uniformity and Assay Content Uniformity, Blend and Assay results are displayed numerically and graphically with the choice of statistics. Specification Compliance Limits Limits and bounds can be defined for Content Uniformity samples and the result clearly shows whether Samples Pass or Fail. Page 15 of 28

16 Application Note 8 UV Dissolution Measurement using USP Apparatus Type 3 The USP apparatus type 3 can be configured with a spectrophotometer in a Closed Loop Configuration. All instruments are controlled by IDISis and an unlimited number of readings can be acquired for each Media. Absorbance data will be acquired at each interval. Temperature and Dip Speed can be set for each Media and allowance for the Drip Time can be set for the Bath properties. Using the Absorbance read from the spectrophotometer, the Weight Content is accumulated and %Dissolution calculated and displayed as the experiment proceeds USP III Tester USP Pharmacia Biotech Spectrophotometer Icalis PCP490 Page 16 of 28

17 Application Note 9 UV and HPLC Dissolution Measurement using USP Apparatus Type 3 and 7 IDISis allow the Automation of USP Apparatus Type 3 and 7 with the ASP2000 Analytical Processing Workstation. With HPLC, samples can be Collected, Diluted and Measured on HPLC, with Agilent Chemstation and Waters Empower or using Contact Closure signal for any generic HPLC CDS system Results will be much faster with reduction in user intervention and labour costs. IDISis control all instruments and timings, complying fully with 21 CFR Part 11 specifications, 11.01(f) if the sequence of system steps is important, it should be enforced by the system. The correct sequence cannot be bypassed. An automated filter unit, comprising 8 Filters, can be incorporated to provide filtration down to 0.45µ. Sample Sets are automatically created by IDISis and sent to HPLC CDS in real time and the Area / Height values are acquired from the CDS after each processing. IDISis will acquire the Area / Height values after each Injection and processing and automatically calculates and accumulates the Weight Content and %Dissolution as the experiment proceeds. The Workstation can also provide automation similarly for UV analysis. Dilution and mixing prior to injection are options that can also be configured Single Syringe Dilutor 1 D1 USP III Tester USP3 ASP2 000 I C A L I S Icalis ASP2000 HPLC Injection Valve ASP Icalis ASP2000 Autosampler ASP01027 Cavro XL Syringe Diluter XL8 Waters Empower EMPOWER Page 17 of 28

18 Application Note 10 UV Dissolution Measurement using USP Apparatus Type 4 IDISis support applications for USP apparatus type 4, configured with a spectrophotometer in Open or Closed Loop Configuration. In Closed Loop, the system behaves similarly to USP methods 1 and 2 and can be used for Stent or weakly absorbing products. Open Loop is the traditional configuration for this apparatus and can be applied to compounds of low solubility or for modified release products. Instruments are controlled by IDISis and an unlimited number of readings can be acquired for each Media. IDISis acquires the Absorbance from the spectrophotometer, as the experiment proceeds, and automatically calculates and accumulates the Weight Content giving rise to %Dissolution based on the Pump Flow rate and the Absorbance values read. IDISis automates changing media during the analysis and the calculations can be based on reading Standards in different Media for each Media change. The IDISis method can be configured to acquire a large number of data points using intervals as low as 30- second, for rapidly dissolving samples especially in the early stages of the analysis where there is the highest activity for the drug dissolution. IDISis results retrieval from Oracle is very fast, about 15 seconds for 6 samples collected every minute for 24 Hours, i.e., loading and displaying 1,440 data points per Sample. Common Sotax MS Sotax CE7 Smart HP 8453 Spectrophotometer Sotax CY7 Page 18 of 28

19 Application Note 11 UV or HPLC Dissolution Measurement using USP Apparatus Type 4 The USP apparatus 4, Flow Through Cell method, lends itself to extended controlled release products and is particularly suited for change of media and hence control of ph throughout the test. This apparatus in particular can be used for low solubility products since by design there is no limit to the volume of media that can be used for each sample. Analysis using this apparatus can be long, up to and above 24 Hours in many cases. IDISis automate apparatus type 4 using a unique design, Dual Sampling Rack, to reduce sample size and manage a larger number of sampling points, for HPLC or UV analysis. For HPLC detection, prior to ALS designing this application, the only option was to collect samples in a Fraction Collector. Difficulties can arise due to the large volume of eluent to be collected. With typical flow rates of 16mls min -1, large tube sizes are required. As the dissolution time increases, larger sample storage may be required which may not be practical. Fraction Collectors have a finite number of positions that are reduced as the volume of samples to be collected increases. This can limit the number of time points that can be collected. A Dual Sampling Rack has been designed to allow reduction in sample size and increase the number of Sampling collection times, while at the same time Diluting if required and injecting into HPLC or measurement on a UV spectrophotometer. Icalis ASP2000 HPLC Injection Valve Generic HPLC Device Sotax CE7 Smart ASP I C A L I S Cavro XL Sotax CY7 CY7 CE7 Smart Icalis ASP2000 Autosampler Page 19 of 28

20 Extended Reporting capability for Profile Overlay, F1 / F2 calculations and Trending results for Stability samples IDISis latest versions now have extended reporting capabilities. Users can overlay profile and calculate F1 / F2 factors as well as trending results for samples on stability trials. # Trend Analysis One or more analysis Different Time-points (defaults to the specifications) Relative or Absolute time Page 20 of 28

21 Users can dynamically select records and obtain the F1 and F2 values. The F1 / F2 values can be configured as part of the user reports. Page 21 of 28

22 Compliance Features FDA 21 CRF part 11 Compliance Administration management allow the system administrator to configure IDISis to meet one of the fullest implementation of 21 CFR Part 11 compliance of any data management system available today. Individual access to the system is by a unique user name and password, configured for each user with Group or individual access rights, and the users full name is displayed when the user logs on successfully and on all documentation generated by the system for the user. Configurable Centralised Security Functionality is provided to allow the administrator to set limits to control the security of the network environment for IDISis. The system administrator can manage password expiry and Reuse, Log Off Times and text to instruct users in their local language how to proceed in case of access failure, etc. These activities can be performed remotely from any IDISis networked workstation and only ever needs to be performed once for each user. With other systems that are not networked, this procedure would have to be repeated for each workstation. Page 22 of 28

23 Signing and Tracking Signature on Records IDISis provide total management for signing, from start to finish. Configuring the number of signing levels, the Users for each level, Signer Activity and Meaning are all managed by the company. The administrator can use up to 5 signature levels appropriate to the structure of the company. These levels can be for Analysts, Supervisors and Qualified personnel. Once the analysis is completed the signing of records can be performed. For HPLC analysis with certain Chromatography Data Systems, no signing can be performed until the records on the CDS are signed. Records will only be displayed automatically for those Groups the user belongs to and further filtering of records, to limit the number of records displayed, is provided using the Signing Query dialogue shown above. Page 23 of 28

24 Once data is acquired in a Group configured for signing, a summary of records to be signed can be obtained and those records the user can sign are clearly visible in dark blue with red indicating the signing for other levels. Either a single record or multiple record(s) can be signed in any one session. The signing process is very simple, clear and precise, the user must view the records selected (which they have access to) before the User can sign these records. Once the records are eligible for signing, Signer Action and Meaning are selected from a list of predefined actions then the user name and password are required to complete signing. Page 24 of 28

25 Once records are signed, the signing is clearly shown on the footer of each page, as they would appear for manual conventional signatures. The status of signing is clearly shown on IDIS reports. Page 25 of 28

26 Dynamic Report Editor The IDISis report organiser allows users to produce customised reports with the right information by selecting from a combination of objects such as Method Header, Data tables, Method parameters, Graphs and the company logo, refer to the previous page. These details include method parameters as well as any data captured during the test such as Bath Temperature, Paddle Speed, Time Intervals as well as Absorbance, Concentration and % Dissolved. Any number of pages can be selected with automatic page numbering. Non-Editable Graphic Electronic Records IDISis is supplied with the Icalis Graphics Printer that provides compliance with 21 CFR Part 11 requirements for human readable form. These reports can be circulated, ed etc., in the safe knowledge that they are non-editable. This Graphics Printer can capture any IDISis report into TIF, BMP or JPG (JPEG) and save them as electronic files. The TIF format can save a multiple page report and the Image Viewer supplied automatically displays the printed file image for verification. Page 26 of 28

27 User Queryable Audit Trail and Record History IDISis Audit Trail lists all user activity that creates, deletes or modifies; i.e., from logging on and off to editing of method and data records. This Audit Trail can have filters to limit the volume of information from a search. The results from any search can be printed. Audit Trail Filters Page 27 of 28

28 Networking IDISis uses Oracle Database 10g for data storage and management. With Oracle your results are always available and secure. Oracle Database 10g has unique security features that address privacy, regulatory compliance, and data consolidation requirements. Oracle automates time-consuming, error-prone administrative tasks, so DBAs can focus on strategic business objectives with superior manageability and significant cost savings over conventional databases. The Oracle network database provides a central relational database that contains records from IDISis workstations. Results are accessible from any workstation on the company s network linked to our Oracle database. Each IDISis system runs from a workstation PC, allowing each hardware configuration to be unique. With this configuration, records can be signed remotely from any IDISis client. For example, it is now possible for analysts and supervisors or managers to view, sign, print records etc away from the laboratory area.. Page 28 of 28