AGILENT TECHNOLOGIES PRACTICAL SOLUTIONS NEWSLETTER

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1 AGILENT TECHNOLOGIES PRACTICAL SOLUTIONS NEWSLETTER Volume 13 Issue 2 In This Issue: Work Smarter, Not Harder: Agilent s Online UV Dissolution Systems Sampling Made Simple: 850-DS Dissolution Sampling Station Labcast HD and Demo at Your Desk Agilent 400-DS: Ongoing In Vitro Applications DDG Online Meetings: Upcoming Events New Penang Production Facility for Dissolution Business Qualification Corner Work Smarter, Not Harder: Agilent s Online UV Dissolution Systems Aren t we always looking for ways to make things better? This is especially true when inspecting our daily laboratory workflow. Asking if Agilent Online UV Dissolution Systems can help us work smarter is a valuable question. We address the answer in four expanded questions that pose typical problem areas and discuss how each of them could be improved specifically as they relate to dissolution testing. Each discussion provides a real-world example of how Agilent s online dissolution solutions including the new Cary 8454 UV Dissolution System can directly enhance these situations. 1. Better Use of Time Q: As a laboratory analyst, chemist or supervisor, are you spending your time the right way? Are there ways to automate or delegate your current tasks so you can accomplish other goals? A: Preparing and executing a dissolution test requires many tasks that you could potentially automate. Depending on the length of the test and number of sample timepoints, automation of the test and the analysis itself most likely provides the biggest benefit. Now instead of constantly checking the clock or responding the sample timers, you can trust an automated system to take and analyze samples allowing you to prepare for additional tests, review data or evaluate time saving measures for other analytical tasks. It s also worth mentioning that while validation of a dissolution method with an automated system is an initial investment in time, you ll typically realize a positive return in time savings in just a matter of weeks. Agilent offers two UV-Vis spectrophotometers, both capable of supporting an online UV dissolution system: the Cary 60 and the new Cary The Cary 60 UV Dissolution System, available in multicell and fiber optic configurations, has an impressive linear range (up to 3.5 Au) and can include the new 850-DS autosampler for sample archival/collection, 0.2 or 0.45 μm filtration and automated cleaning. The Cary 8454 system offers scalable diode array solutions up to four dissolution apparatus may be configured with seamless transition from its predecessor, the 8453 system. With distinct advantages, rely on your needs and experience to choose the solution that s right for you. 1

2 Online UV Dissolution... continued 2. Sample Throughput Q: How should the endless stream of dissolution sample analysis be managed? What s the best way to maximize the throughput in an efficient and reliable manner? Cary 60 UV Dissolution Systems support single- or dual-apparatus configurations with multicell or fiber optic analysis available to accommodate difficult filtering or timepoint frequency needs. A: There s no one-size-fits-all response to these questions. The first thing to assess is your lab s particular situation. It s best to determine what the actual rate-limiting steps are in your workflow i.e., where is the logjam? If certain parameters of the dissolution method (e.g., filtration, timepoints) prevent online automation, it may be best to simply automate dissolution sample collection and implement a sipper to perform the analysis. Or if the same method is executed repeatedly, you may find that a multi-apparatus online system will provide maximum throughput and efficiency with minimal setup required. Agilent s new Cary 8454 system is scalable with online solutions ranging from one (1) to four (4) dissolution apparatus, all controlled from a single PC with the improved UV ChemStation software. For situations where UV-Vis sample analysis alone is the bottleneck, the Cary 8454 system can also be configured with an XY-autosampler and sipper module to expedite this step. 1 Agilent Cary 8454 UV Dissolution System, single apparatus multicell configuration. An Agilent XY-autosampler, Cary 8454 UV-Vis Spectrophotometer and sipper module works to increase throughput and reduce manual handling errors. 3. Reduction of Errors Q: How should you reduce variability from analyst to analyst? What can be done to limit the time it take for a failure investigation? Why does it seem like the more automation, the more problems occur? The primary design focus of Agilent s dissolution instrumentation is to eliminate sources of external variability and ensure differences in results are from the dosage form itself. This begins with the automation-friendly dissolution apparatus (708-DS or 709-DS) to the sampling station (850-DS) and then flows through to the UV-Vis analytical finish (Cary 60 or Cary 8454). A: As with any process, it is important to have a good understanding of how things work in order to efficiently solve issues that may arise. If you re looking to reduce variability an inherent trait of humans an automated system will eliminate many areas of concern. When dissolution sampling position, timing and filtration, filling of flow cells and subsequent analysis are performed in a consistent manner, you reduce manual handling errors and variability. Even a sipper coupled with a UV spectrophotometer can provide improvement of analytical consistency and throughput. Differing levels of dissolution automation are readily available, but it s not always the most expensive or complicated instrumentation that is the best fit for your laboratory. Proper evaluation of your workflow will ensure the most appropriate solutions are put into place. By understanding where your failures typically occur, systems (or parts of systems) can be implemented to improve daily operations. 2 With a single-vendor solution, you can be sure that control of instruments and management of methods and data are seamless and secure. To keep automation simple and truly maximize its benefit, understand your workflow and find the solution best suited to your needs. Agilent not only has varying levels of options available, including the new Cary 8454 system, but provides assistance to ensure your goals are achieved. continued on p. 3 Online UV Dissolution... continued 4. Optimizing your Laboratory Equipment Q: How can you be sure you re getting the most out of your current equipment? Do you have options for expanding or adding capability to what already exists? A: Once the entire workflow is understood and the trouble spots are identified, a closer inspection of available instrumentation can be performed to assess if new purchases need to be made. Your instrument vendor should be able to discuss improvements and upgrades to your existing instrumentation, as well as helping you identify any missing pieces that could improve throughput and efficiency. The online UV dissolution systems from Agilent deliver complete control and analysis for a wide range of dissolution methods all from a single vendor. The Agilent Cary 8454 system provides a seamless transition from the 8453 system with 3 different configurations. Powered by an enhanced version of Agilent UV ChemStation software, it s also ideal for single or select multicomponent products. Agilent stands ready to help you streamline your workflow and improve your overall productivity with a number of outstanding solutions including the Cary 60 UV-Vis spectrophotometer and the new Cary 8454 UV-Vis spectrophotometer. Learn more about Agilent s online UV Dissolution Systems at lifesciences/uvdissolution or join us live for Dissolution Demo at Your Desk at www. agilent.com/lifesciences/demo-at-desk. Then put our dissolution systems to work in your lab. 3

3 Sampling Made Simple with the 850-DS Dissolution Sampling Station Dissolution can be a tedious, manually intensive process but it doesn t have to be. Agilent dissolution instruments make it easy to streamline your workflow and reduce the likelihood of errors. The 850-DS is designed to make your life easier. A closer examination reveals just how simple automated sampling has become. Simplified Control The 850-DS is designed to control the dissolution workflow. Methods can be written, modified, stored and exported from the touchscreen display. User levels exist for administrators, advanced and basic users, each with their own amount of control. The 850-DS also manages the dissolution apparatus run parameters directly via the RS232 interface. Simplified Design Instead of separate components (pump, printer, media replacement or filter changer), the 850-DS is an all-in-one space-saving package. The autosampler features an integrated design that takes up less bench space, and is easier to install and maintain. The smaller footprint saves valuable bench space. With internal syringe drive, optional filter changer and printer, as well as less tubing and fewer external electrical cables, your laboratory clutter is minimized. Simplified Operation To initiate a test, simply locate your stored method and ensure the dissolution apparatus is ready. Media volume and apparatus type dictate the correct sampling location, while temperature verification, optional filtration (down to 0.2 or 0.45 µm) and media replacement can all be programmed in a method. Even a final cleaning cycle can be incorporated to ensure the lines are properly cleaned at the conclusion of the run. Our goal in designing equipment is to mimic the manual workflow in order to simplify method transfer from manual to semi-automated methods. For this reason, we utilize a motorized sampling manifold to lower and withdraw samples from the same location as you would manually. On this same manifold, we can incorporate an automated temperature probe to verify and record the temperature in each vessel prior to or during a run. The 850-DS works with a variety of sample trays. From standard test tubes, to precapped HPLC vials and micro-well plates, we make it easy to collect in whatever format you require. With the ability to sample directly to sealed micro-well plates, it becomes easy to ensure sink conditions are maintained. Should your method require media replacement, this feature is standard. Replacement media is pulled from an external source (or possibly one of the extra vessel locations on the dissolution apparatus). After the sample is withdrawn, an equal amount of fresh media can be replaced. This feature can even be utilized with the filter changer. Traditionally this has not been possible due to the unidirectional nature of syringe filters. On the 850-DS, the filter plate is automatically moved out of the way and the lines reconnected to allow the media replacement to occur. All this can be specified during method setup without any manual reconfiguration or external components. 850-DS Sample Tray Options Sample directly into Agilent autosampler trays, eliminating the need to transfer vials to an LC autosampler rack. Simplified Filtration Filtration can be handled in one of two ways: 10, 35 or 70 μm Full Flow filters on the sampling cannula (generally recommended) that may be coupled with an additional final filtration step prior to the sample being dispensed into the vial or test tube. To ensure the dissolution samples are clarified for the intended analytical measurement, it may be necessary perform an additional filtration step. Traditionally this was done manually using a syringe disc filter. By incorporating eight disc filters into a single filter plate, we ve simplified the filter changer design and made it more robust as well. Working together with GE Healthcare, a new line of Whatman TM filters specifically designed for dissolution sample collection with the 850-DS are available in a variety of membranes. continued on p. 5 Cleaning the system has never been simpler. Place the cleaning tubing into the designated flask and program the cleaning cycle. When the dissolution method concludes, the cleaning protocol will be initiated with no user intervention required. Sampling Made Simple... continued The exclusive Whatman 850-DS 8-channel filter plates simplify the need for replacement between timepoints. These filter plates are less bulky than conventional automation ready filters, are less prone to jamming and are easy to load. The filter plates are designed to work exclusively in the optional filter module that can be configured with any standard 850-DS. Once installed, the user has the option of incorporating a final filtration step if their method requires this (typical of HPLC methods). If no filter is needed, no manual intervention is required to bypass the filter changer completely. continued on p. 6 Full Flow filters are available in ultrahigh molecular weight polyethylene (UHMWPE) or PVDF. The UHMWPE come in 10, 35 and 70 micron porosity and the PVDF are available in 10 and 35 µm sizes. The Full Flow filters remain on the sampling cannula during the duration of the test. Item description PTFE membrane fitler, 25 mm, 0.45 µm Nylon membrane filter, 25 mm, 0.45 µm Polyethersulfone (PES) membrane filter, 25 mm, 0.45 µm Glass fiber (GMF) filter, 25 mm, 0.7 µm* *Retention rating rather than pore size. Whatman 25 mm Individual Puredisc Filter part numbers (50/pk) (200/pk) (50/pk) (200/pk) Whatman 25 mm Individual Puredisc Filter part numbers Visit for contact information regarding filter plate ordering. The filter changer is installed on the top of the 850-DS, taking up no additional bench space. When a method calls for filtration down to 0.45 µm pore size it is easily incorporated in the method. Bypassing the filter module is done automatically via the firmware control. Recommended application (50/pk) Chemically stable and inert, suitable for acidic aqueous solutions (50/pk) Robust hydrophilic membrande for applications where protein binding is not critical (200/pk) (50/pk) Hydrophilic low proten binding membrane recommended for aqueous samples (50/pk) (200/pk) Table 1. Whatman 25 mm syringe tip filters, corresponding filter plates and recommended applications (50/pk) The standard for difficult-to-filter samples to retain coarse particles; also, a good filter for gelatinous capsules 4 5

4 Sampling Made Simple... continued Simplified Documentation Labcast HD and Demo... continued Documenting your dissolution run or results is simple with the 850-DS. An optional printer can be installed on the side panel, or you may choose to control systems with Agilent s Dissolution Workstation Software or an integrated online UV dissolution system. The printer uses a medical grade thermal paper which is rated for 10 years. Should you wish to transfer the data electronically, this can be done via RS 232 or the built-in SD card reader. Simplified Analysis Agilent makes it easy to perform your dissolution analysis. The Cary 60 UV Dissolution System offers you tremendous flexibility. Once installed, you can perform online UV analysis and, if you desire, collect a sample for each timepoint. This greatly simplifies a failure investigation should one be required. Software control is made possible by the Cary WinUV software platform which is designed to enable 21 CFR Part 11 compliance. If your samples require HPLC analysis, simply bypass the UV-Vis spectrophotometer and collect your samples using the 850-DS and a software add-on for LC-ChemStation to simplify the dissolution analysis and report generation. For more information on these systems, visit Filter Validation Protocol Agilent 850-DS Dissolution Sampling Station Technical Overview The Agilent 850-DS Dissolution Sampling Station is optionally equipped with a filtering option that greatly improves dissolution sample processing through the use of innovatively designed filter plates. The Whatman 850-DS 8-Channel Filter Plates from GE Healthcare, are consistent with filtration membranes and housing materials currently used for dissolution sampling. The only differences between traditional luer-type syringe tip filters and the filter plates are the absence of the luer fittings, and eight disks are incorporated on a flat plate. The compact arrangement of the filters on the plate also make it much easier for the automated equipment to process and filter samples over traditional automation-ready filters. To minimize the effort that your laboratory would have to invest to evaluate and validate the new filter plates, the following is an example of a filter validation. It is a straightforward procedure and it should be maintained with your method validation documentation. The filter validation protocol includes filter selection guidance, as well as three tests to challenge the filter s efficiency, adsorption and leachability. Take a look at our technical overviews to guide you in the filter validation process and understanding the merits of automated sampling. Visit lifesciences/850-ds. Labcast HD It s easy and free to schedule a Labcast with one of our knowledgeable chemists who will walk you through the capabilities of our instruments and answer your questions in real time. Just contact your Agilent sales representative and we will schedule a convenient time for you, usually the same week as the request (subject to availability). Product demonstrations are not all that we offer through Labcast HD. We are also happy to support you post purchase, by offering the expertise of our seasoned chemists to answer any question or concern you have about any of our products or accessories. Demo at Your Desk On-demand Labcasts are not your only opportunity to see us on screen. We are pleased to announce a new series of ongoing video conferences called Demo at Your Desk, where we will demonstrate our products along with any corresponding applications. Register for free demo-at-desk and you will be treated to an immersive, HD video presentation revolving around each topic or theme. Topics are duplicated in the schedule so if you miss a particular topic, please check back at a later date. More topics and dates will be announced later based on demand. What Can You Expect to See? The instrumentation and related software will be demonstrated during each video conference. Our goal is to provide you with an understanding of the capabilities of these instruments and how they fit into the Agilent workflow solutions. We will demonstrate a typical method and review the key factors that should be considered when selecting the appropriate instrument(s) for your operation. Firmware, and where appropriate, software capabilities will be demonstrated along with select accessories. This experience is not intended to be one way. We encourage you to ask questions because our goal is to be sure you fully understand what our equipment can and cannot do. We look forward to seeing you at one of our demonstrations. We really think you will love the audio/video quality, convenience and personal touch our new Labcast HD service offers. Register for, or schedule, one today and see the difference for yourself. Labcast HD and Demo at Your Desk We know your time is valuable and we know you want to see our products as quickly and as conveniently as possible when making a purchasing decision. We also understand that conventional product demonstrations can be time consuming and inconvenient as you wait for products to be transported and set up in your facility. Since 1999, we have addressed these concerns through the use of ISDN/IP Labcast video conferencing but have realized through the years that although this level of service was more convenient, there was still plenty of room for improvement in customer experience and video quality. That is why last year we revolutionized the Labcast experience. Instead of relying on the clunky video conferencing technology of old, or requiring you go to a special conference room to watch our demonstrations, we can now broadcast a live, multi-camera video conference directly to your computer or Apple/Android mobile device. We call it Labcast HD. continued on p. 7 High definition broadcasting experience with Labcast HD and Demo at Your Desk. Current Demo at Your Desk Schedule Date, 11 a.m. EST Demo Title June 3, 2014 Managing laboratory instrumentation: Dissolution Workstation Software June 17, 2014 Selecting an autosampler and the benefits of semi-automation: 850-DS and 708-DS July 1, 2014 Benefits of fiber-optic UV dissolution: Cary 60 Fiber-Optic UV Spectrophotometer July 15, 2014 Enhanced Mechanical Qualification: 280-DS July 29, 2014 Online UV dissolution analysis for Multi-Component products: Cary 8454 UV-Vis Spectrophotometer Aug 12, 2014 Small-volume dissolution testing: 400-DS Register for free! 6 7

5 Agilent 400-DS: Ongoing In Vitro Applications The 400-DS Dissolution Apparatus was designed to meet the challenges associated with the testing of combination products with prolonged release of low-dose compounds designed for targeted drug delivery. Available compendial apparatus are limited to volumetric applications that are significantly larger than those volumes required for many combination products which release in the pico- and nano-gram levels each day. To maintain quantitative levels of analyte during dissolution and drug release testing, a reduction in vessel volume accompanied by a modification in the compendial USP Apparatus 7 Reciprocating Holder apparatus was required. While the 400-DS conforms to the conditions of USP Apparatus 7, the holders stated in the USP method are unsuitable for most combination products including: drug eluting stents, contact lenses, pacemaker leads, catheters, micro- and nano-particles and other implants. An assortment of precision holders was produced by Agilent to contain these products and orient the dosage forms for maximum exposure to media. Since many of the combination products above may provide drug release over a period of months, the dissolution methods must be accelerated to provide the release profile in less than a twoweek period primarily in quality control where time-to-batch release is critical. The accelerated methods must be relevant to the drug release over the time period and must also be discriminatory, capable of detecting failure, and provide batch-to-batch consistency and biorelevance. Although developed initially for drug eluting stents testing under accelerated conditions, the 400-DS has been utilized for testing many products requiring ultra-low volumes in the 5-10 ml range with absolute control over evaporative losses and assurance of analytical sample integrity. Early methods with ultra-low volumes included shaking apparatus contained in incubators which were only partially successful due to the battering of the delicate devices undergoing mechanical shaking. Such apparatus also took up considerable laboratory real estate for significant periods of time. The evolution of USP Apparatus 7 into the 400-DS allows for the device to be positioned within a holder while the reciprocating movement may be adjusted to provide optimum hydrodynamic shear to the surface of the device without the variability associated with mechanical abrasion. Agilent 400-DS stent holder. Regulatory expectations for small-volume testing methodology are quite similar to traditional dosage forms and methods are expected to: Characterize in vitro release early in development. Evaluate release with various conditions including agitation rate, media composition, ph, temperature, etc. Establish optimum testing conditions. 80% release of active component or an asymptote is achieved. Discriminate as tested with critical manufacturing variable (CMV) samples and demonstrate its capable of rejecting a batch. Set specifications to show consistent lot-to-lot performance. Agilent 400-DS... continued In keeping with the regulatory expectations, the 400-DS has been recently applied to novel dosage forms such as intra-vaginal rings (IVR) and medicated balloons as published in recent studies in Germany. These studies, performed by Doctors Sandra Klein and Anna Externbrink from the Institute of Biopharmacy and Pharmaceutical Technology, University of Griefswald, have been summarized in two case studies. Case Study 1: Application of USP Apparatus 7 in Performing Real Time and Accelerated Release Studies of an Intravaginal Ring (IVR) Conducting drug release studies at elevated temperature to evaluate the release rate of extended release formulations is not widely documented for formulations made with non-biodegradeable polymers. This study investigated controlled elevated temperature to predict real-time release from an IVR. The testing was performed with endcapped segments of the IVR and the cumulative release of etonogestrel and ethinylestradiol was calculated based on the mass ratio. Segments were placed in a mesh basket holder within the 400-DS and allowed to reciprocate in 10 ml of biorelevannt medium at 40 dips-per-minute (DPM). Two sets of accelerated conditions were applied: (A) Temperature at 50 C and (B) Release medium containing 50% EtOH (V/V). Samples were obtained and media replaced at 12-hour intervals at 37 and more frequent intervals as accelerated conditions were applied; samples were analyzed by HPLC. The methods run on the 400-DS demonstrated precision and sensitivity under real-time and temperature-controlled accelerated conditions. Release profiles obtained with the 400-DS and the FDAapproved standard test conditions show a similar trend with time. The precise temperature control with the elevated temperature studies provided a stronger correlation than the hydro-alcoholic media to predict real-time release. Overall, the results demonstrated that the 400-DS is capable of long-term and accelerated release studies of low-dose ER formulations. Case Study 2: Investigating the In Vitro Release Properties of Triamcinolone Acetonide Injectable Suspension from a Drug-eluting Balloon-like Spacer for the Treatment of Paranasal Sinusitis The drug-eluting balloon is designed to be implanted in the sinus cavity. The device is filled with a steroid injectable suspension which elutes from an expandable reservoir through controlled openings over a sustained period of time from days. Preliminary studies were performed by profiling the drug release in the 400-DS equipped with 10 ml dissolution cells with phosphate buffered saline (PBS) media ph 7.4 maintained at 37 C. Experiments were carried out under two conditions (1) within dialysis bags of a defined length, sealed with a nylon strand and attached to a reciprocating holder; and (2) the balloon was filled with a clinically relevant dose, sealed and placed into the 400-DS mesh basket holder. The dissolution tests were performed with the PBS media containing 0.3% SDS at a rate of 20 DPM and samples were analyzed with HPLC. It was found that the absence of controlled openings in the dialysis bag experiment limited release of the drug and that an absence of agitation within the dialysis bag and balloon could limit drug release. Although the balloon spacer was faster compared to the surrogate dialysis bag, it was summarized that increasing the agitation and performing additional tests with the balloon are necessary. The Agilent 400-DS has routinely been involved with current methodology for drug eluting stents and pacemaker leads primarily and these additional studies demonstrate that the apparatus is a versatile drug-release apparatus that maintains control of critical variables during small-volume testing in terms of temperature, agitation and evaporation control. i Application of USP Apparatus 7 in Performing Real Time and Accelerated Release Studies of an Intravaginal Ring; Anna Externbrink and Sandra Klein, Institute of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Germany, AAPS Poster W4245, AAPS 2012 ii Investigating the In-Vitro Release Properties of Triamcinolone Acetonide Injectable Suspension from a Drug-Eluting Balloon- Like Spacer for the Treatment of Paranasal Sinusitis; Anna Exterbrink, Carmen Liermann, Christian Scharf, and Sandra Klein, University of Greifswald, Germany; AAPS Poster T3115, AAPS 2013 continued on p. 9 Agilent 400-DS Dissolution Apparatus

6 DDG Online Meetings: Upcoming Events In 2011, the Dissolution Discussion Group added free online meetings for live discussion of dissolution related topics. Since then we conducted a full range of online discussion topics ranging from enhanced Mechanical Qualification (MQ) to aberrant data investigation and critical elements of the dissolution test from vibration to deaeration. Each of these sessions is hosted by Bryan Crist, Scientific Affairs Manager for Agilent Dissolution Systems, and he is joined by a variety of panel members across the pharmaceutical industry who offer their expert level of dissolution testing experience to the attendees. Recordings of all of the previous, quarterly online meetings are available on the home page of the DDG website. During these sessions we provide a quick recap of ground rules for discussion and slides are presented in a WebEx format to New Penang Production Facility for Dissolution Business In December, Agilent completed the transition of its Dissolution Systems product line from Cary, North Carolina, USA to Penang, Malaysia. Agilent s Penang facility is one of the company s largest production and engineering sites in the world and is optimized to accommodate increasing customer needs worldwide. Agilent s Penang facility provides a worldclass manufacturing facility supported by experienced manufacturing and engineering teams. The move to Penang allows the Dissolution Group to take advantage of the procurement synergies with the many other scientific products currently manufactured at this site. stimulate discussion. The panel members have open microphones for discussion. Attendees may request to have their phone line opened to participate in discussion or they may simply pose discussion points in the Q&A box located within the WebEx screen. In 2014, the DDG Online meetings entered a new phase of discussion regarding dissolution method development and validation and we conducted the first three parts on Filtration Requirements (November 7, 2013), Dissolution Media Volume and Sink Conditions (February 6, 2014) and recently, Challenges for Poorly Soluble Compounds (May 15, 2014). Our next meeting on August 14, 2014 will discuss Dissolution Method Development and Validation Part 4: Timepoint Estimation Abstract Solid oral dosage forms have numerous release mechanisms that have to be quantitatively measured to ensure the performance of the drug product. Although immediate release products generally have We are always exploring new ways to better serve customers. By transferring operations from Cary to Penang, we can better serve our expanding customer base especially in the Asia region and continue to provide the highest quality products and services that Agilent customers have come to expect. ALLAN LITTLE, DIRECTOR OF MARKETING FOR DISSOLUTION SYSTEMS, AGILENT only one or two timepoints and extended release forms have three of more to ensure quality control, additional points are generally required to ensure similarity from batch-to-batch as well as generic to innovator during product development. Profile comparison of dissolution methods provides assurance of similarity with the application of f2 calculations and multiple timepoints, ensure the full release of API, and through infinity timepoints assure consistency without bias to assay and dose uniformity tests. Our discussion will focus on assigning timepoints to obtain the most meaningful data to support product development, regulatory approval and post-approval change. We hope you can join us for future meetings and as a reminder, check for current discussion and upcoming events on the DDG site: Our sessions have been very interactive and we encourage you to sign up for the next meeting. Your opinions, views and participation are always welcomed by the DDG! Agilent s Cary, North Carolina, business office remains open and all dissolution customer services and support channels continue without interruption. Dissolution chemists are available to assist with questions, applications, method development, regulatory guidance and instrument-related support. Customers may access online assistance at: com/lifesciences/dissolution_hotline. Qualification Corner Still using Prednisone? Looking for advice on how to properly implement ASTM E (Mechanical Calibration)? Check out a recent issue of Practical Solutions dedicated to Dissolution Qualification that contains: Step-by-step guidelines on how to transition from PQ to MQ Rethinking qualification: What if it only takes 15 minutes? Industry survey: What is everyone else doing? Regulatory perspective: The official position of worldwide agencies Excerpt Making the transition to ASTM and FDA-approved enhanced Mechanical Qualification (MQ) procedures from the USP Performance Verification Test (PVT) is much more than simply taking a few additional mechanical parameter measurements with tighter tolerances. Agilent created the following template as a guide to ensure you have all the details on the requirements. It is not as simple as eliminating Prednisone, but each of the suggested practices must be established in the transition to enhanced MQ to ensure. To continue reading this article plus links to white papers and more on this topic, visit Dissolution Qualification Timeline / Schedule Physical parameter verification of the dissolution apparatus has integrity: always been required before performing dissolution tests and Initial: IQ/OQ/PQ periodically as part of Performance Qualification testing. One of the advantages of enhanced Mechanical Qualification (MQ) Daily (or at time of use): Accessory examination per ASTM implementation is time savings. From a user perspective, these MQ E guidelines. Verify any physical parameter as a check in only minutes. measurements may be performed in considerably less time which allows them to be performed more often. Once the procedure Monthly: Abbreviated physical measurements; wobble for paddle, is firmly integrated into your laboratory routine, it provides basket shaft and basket along with vessel table level using the less downtime and scheduling issues. The time savings can be 280-DS, takes approximately 20 minutes to perform for both paddles significant with these hours, or even days, now available that used and baskets. to be filled with Prednisone testing and analysis. Quarterly: Complete verification of physical parameters using MQ procedure according to ASTM E ; approximately Let s explore how even greater efficiency and reduced instrument minutes per USP Apparatus using the 280-DS MQS. downtime can be achieved. We ll examine how some intermittent procedures and monitoring can be inserted into the routine care and Biannually: Complete verification of physical parameters using maintenance of the dissolution equipment to prevent foreseeable MQ procedures according to ASTM E ; also includes issues and help with future failure investigations. vibration measurement and re-verification of temperature probes; if applicable, auto-sampling instrumentation is inspected and reverified The timeline displayed below offers one example of how (e.g., volume accuracy); this procedure takes approximately incorporating periodic evaluations daily, weekly, monthly, or minutes per USP Apparatus and an additional 20 for temperature and quarterly between traditional qualifications can lessen the vibration. likelihood of problems related to your dissolution instruments. Due Annually: Biannual procedure plus PM performed by to the ability to reduce measurement time and its software trending manufacturer. feature, Agilent s 280-DS Mechanical Qualification System Intermittent: reverification of critical physical parameters (MQS) has been used to illustrate this concept. With routine for failure investigation purposes of apparatus installed during measurement and trending, the laboratory may see a problem unexplained behavior; examination of data trends for the apparatus before a parameter is out of specification. For instance, steadily approximately 15 minutes for complete measurement cycle using increasing paddle wobble measurements from month to month 280-DS. Additionally, environmental conditions are reevaluated could be corrected before becoming an out-of-specification (OOS) whenever new instrumentation is added to the bench to ensure that result. the level and vibration parameters have remained unchanged. The example timeline consists of an IQ/OQ/PQ (where PQ = USP The MQ procedure allows for a robust evaluation schedule to exist PVT) performed during initial qualification. Although the PVT is no with a very manageable time commitment. When coupled with longer required if it has been replaced by full implementation of the 280-DS MQS and data trending capability of the software, MQ, it is still used by some dissolution laboratories during initial problems can be proactively addressed and failure investigations installation along with MQ as part of a hybrid approach. Over improved dramatically. This is just one example of how you may the next 12 months, several shorter procedures are in place to schedule your dissolution qualifications for additional advice, chat consistently monitor instrument performance and ensure apparatus with your peers on the Dissolution Discussion Group (DDG) or ask our in-house experts on the Dissolution Exchange. MQ Survey Results Practical Solutions newsletter Mechanical Qualification (MQ) edition. 3 Agilent surveyed the attendees from its recent MQ seminars and asked for their input on some of the key aspects of dissolution qualification. Here s what they said: When considering changes to the dissolution What are the key factors that drive changes to your qualification schedule, what are or have been your Dissolution qualification schedule? * biggest hurdles to overcome? * Regulatory compliance 77% Risk assessment: will the new process 53% Time savings / Productivity 71% effectively identify problems Understanding of Regulations / Compliance 53% Budget / Cost savings 41% Continuous improvement 41% Financial analysis / Justification 47% Specifications / Tolerances of procedures 35% Change Control process 47% Implementation 24% * Participants were asked, if applicable, to enter multiple answers. * Participants were asked, if applicable, to enter multiple answers

7 Learn more The information is subject to change without notice. Agilent Technologies, Inc Printed in the USA, May 15, EN