REFRACTOMETER & POLARIMETER RESOURCE GUIDE

Transcription

1 REFRACTOMETER & POLARIMETER RESOURCE GUIDE KEEPING YOUR COOL IN POLARIMETRY 2 REFRACTIVE INDEX IN THE HARSHEST CONDITIONS 3 QUALITY CONTROL IN DRUGS 4 THE HIDDEN VALUE OF INSTRUMENT MANUFACTURERS 5 1

2 Keeping Your Cool in Polarimetry electrical current across a junction between two conductors. Depending on the direction of current flow, heat is generated on one side of the Peltier element while the other side is cooled. The generated heat is dissipated by an internal heat sink. Since current can be switched back and forth very quickly, Peltier elements can rapidly respond to temperature changes in the measuring cell and maintain the required temperature with greater precision, leading to a higher precision in the measurement of optical rotation. Temperature is often an overlooked component of most analytical measurements. The ability of an instrument to accurately measure temperature ensures that there is no discrepancy in the final result. The use of Peltier elements in polarimeters assures a reliable result every time. Polarimeters are used to measure the optical rotation of chiral compounds and are a proven technology with numerous product standards written for the measuring principle across multiple industries. A sample is placed in a measuring cell of defined path length at a defined temperature and plane polarized light of a defined wavelength is shone through the sample. The light is rotated by the sample, and this optical rotation is measured by a detector. From this information, a compound or its concentration can be determined. One of the most overlooked components of a polarimeter is temperature control. Temperature has a strong influence the specific rotation of a material being measured, so proper temperature control is critical to an accurate measurement. Past generations of polarimeters used large thermostatic baths to maintain temperature control, running tubes of water or other liquid from the measuring cell to the bath to equilibrate temperature. These baths, which take up valuable space in the laboratory, are often their own source of maintenance woes, leaks, and frustration. The current generation of polarimeters relies instead on Peltier elements to provide thermoelectric heating and cooling. Peltier elements are solid state electrical devices which are able to heat and cool by applying an The Peltier elements used for temperature control in polarimeters are an integrated component of the instrument itself meaning that there is no external bath and a definite saving in terms of laboratory space. Further, the risk of leaks and the constant noise of the circulator pump running the bath are eliminated. Peltiers are most thermally and electrically efficient around room temperature, so a Peltier element is a very economical means of maintaining a stable temperature for measurements specified in the C range. With no great swings in temperature, they can have a considerable lifespan. Peltier elements can be arrayed so that they surround the measuring cell, allowing the measuring cell and sample to be in direct contact with the elements and quickly come to temperature. This configuration also allows the measuring cell to be quickly and easily removed for cleaning and maintenance with little to no downtime between samples. The measuring cell is simply lifted from the Peltier assembly and replaced when the next sample is ready. The footprint of an instrument with Peltier elements is reduced without the need for a thermostatic bath. This is because the solid state Peltiers are able to fit into a small space and reduce overall size of the instrument while still maintaining accuracy. Their presence does not interfere with or hinder the optical bench of the instrument, allowing a normal measurement to be performed in a reduced space. Polarimeters are a proven part of an analytical laboratory and are required for numerous product characterizations. All Anton Paar MCP Polarimeters incorporate Peltier temperature control to provide higher accuracy and increase ease of use. Their smaller footprint can allow for increased productivity in the laboratory and their solid state components are extremely reliable, making them a wise investment in the laboratory. 2

3 Refractive Index in the Harshest Conditions manually programmed into the instrument, as well. In all cases, the result is a direct measurement of concentration without further need for sample preparation. The chemical industry is a rough place. Between the acidic and the caustic, the organic and the inorganic, materials can interact with each other and even the environment, sometimes in dangerous ways. Equipment that works in this industry needs to be robust to handle the challenges of the samples it will encounter. A heavy duty refractometer is equal to the challenge. A refractometer in the chemical industry needs to be robust and reliable. The nature of the samples that it will measure, possible reaction hazards, and the industrial environment all require that the instrument be strong, durable, and safe. Heavy duty refractometers are able to provide ruggedness and versatility without compromising on accuracy. Refractometers are a valuable tool in the chemical industry for their ability to rapidly determine the concentration of a material from a small sample volume. Analytical techniques like titration can take a long time to complete, constantly requiring titrants be purchased and consumed and generating waste requiring disposal. A refractometer requires only a few drops of a sample to perform an analysis, greatly reducing the need for consumables and hazardous waste storage. A heavy duty refractometer is designed for the rigors of the chemical industry from the ground up. The most noticeable design feature is the separation of the measuring cell unit from the control unit. By keeping the cell separated from the control panel, the measuring cell and measured samples can be safely kept under a fume hood. Functions like sample information entry and data handling can be performed outside of the fume hood, away from the sample. This also helps to keep the majority of the instrument electronics from direct exposure to the samples. The modularity of the measuring cell unit also means that this part can be switched out completely in the event of unforeseen damage. Less visible within the measuring cell unit is a hermetic seal designed to keep the measuring cell electronics clean, dry, and protected from the sample being tested and accidental spills. An aluminum outer housing provides strength and chemical resistance against a wide range of materials. The prism of the refractometer is made from synthetic sapphire, which has a wide chemical resistance and strength to prevent both chemical etching and physical scratching. For optimal chemical compatibility, a sample well of Hastelloy can be retrofitted into the instrument, providing further protection against corrosion of the measuring cell. A heavy duty refractometer like the Abbemat 450 or Abbemat 650 offers a robust and safe measurement solution in the chemical industry. With little to no need for additional sample preparation or handling and only minimal sample volume, it is a reliable and efficient tool in a challenging environment. Any solution where the refractive index changes with respect to concentration can be measured by means of refractometry. Refractometers come with numerous concentration tables included, and further tables can be additionally added based on the samples being measured. Custom tables can be 3

4 Quality Control in Drugs by Tara S. Hundley measure with high accuracy and repeatability, making them indispensable in the pharmaceutical industry. To meet the needs of pharmaceutical companies who want to fulfill international Pharmacopoeia requirements, 21 CFR part 11 regulations as well as GMP, FDA and GAMP5 regulations, Anton Paar offers validated software as well as qualification documentation packages (DQ, IQ, OQ and PQ). These state-of-the-art and time-saving solutions save hundreds of hours of working time per instrument for required validation processes. Polarimeters are essential in drug quality control to ensure the enantiomeric purity and therefore efficacy of pharmaceutical drugs. What s all the fuss about optical rotation? Pharmaceuticals that are optically active have a molecule that is their mirror image. This molecule can have different pharmacological effects, toxicity, or have no effect at all. The optically active pharmaceutical and its mirror image are referred to as enantiomers. They might possess identical physical properties - however their physiological properties might differ dramatically. Enzymes have an active center which can prefer one substrate s enantiomer over the other, as the induced fit of different enantiomers of the same substrate differs. The physiological effect of the purified D- and L-enantiomers of a -blocker, for example, differs by a factor of roughly 100 when applied in identical concentrations. GOOD TO KNOW The MCP polarimeter family from Anton Paar is the ideal partner for the pharmaceutical industry and ensures high-quality products. In order to ensure the pharmacological effect of a drug, quality control in drugs includes testing for enantiomers, making polarimeters essential in drug quality control. Serving the need for optical quality control in pharmaceuticals By measuring the specific rotation, the MCP polarimeters from Anton Paar can control the enantiomeric purity of optically active pharmaceutical drugs. They also have built-in Peltier temperature control and 4

5 The Hidden Value of Instrument Manufacturers by Tara S. Hundley simple: analytical test results from unqualified instruments can be wrong or invalid, thereby compromising drug safety and efficacy. The consequences for not being in compliance are the nightmares that keep you up at night inspections and fines. So what are your options? You could beef up your internal regulatory and compliance staff, but the pharma mantra these days is to be as lean as possible. After all, that s what has fueled the outsourcing trend. Save time and money by getting first-hand information for your instrument qualification. The Anton Paar Pharma Package aids you in achieving and maintaining the qualified status of your instrument. What s all the fuss about optical rotation? For those of you who work with any analytical/lab or process instruments, you know that staying in compliance with global regulations has become burdensome in the past decade. Everyone is fixated on streamlining production processes and reducing the bottom line. This means getting new instruments into the workflow as soon as possible; but to do so you need to know everything there is to know about equipment and instrument qualification. In the overall pharmaceutical manufacturing process, you may be just one cog on the gear of productivity, but without some help, you could go from cog to clog very quickly. Overlooking the Obvious Instrument qualification regulations and guidelines from GMP, 21 CFR Part 11, GAMP 5, and USP<1058> are lengthy and detailed. They require you to collect all data about the instrument s intended use and maintenance, which is an ongoing, time-consuming, and laborious process. But the rationale for having these regulations and guidelines is One solution that is often overlooked is seeking assistance from the company that manufactured your instruments. Doing so is more like partnering than true outsourcing, and frankly, it makes sense. Why not go to the source: the company that had to adhere to all those guidelines and regulations when it was creating the instrument? The Key Components of an Instrument & Validation Solution Tackling the 4Qs (Table 1) on your own can be daunting both from labor and time standpoints. Even understanding the difference between the terms qualification and validation can be challenging. is often referred to as a condition or state of control that must be met in order to assure the validity and reliability of test results. Validation is establishing documented evidence that provides a high degree of assurance that a particular process will consistently produce a product that meets its predetermined specifications and quality attributes. Instrument qualification is a prerequisite for process validation. That s why many pharmaceutical companies seek assistance from Anton Paar. Anton Paar understands your need for completely traceable results, and supports you with a qualification and validation package. Anton Paar s Pharma Package (PQP) aids you in achieving and maintaining the qualified status of your instrument. Not only does this service comply with all the necessary regulations, it follows the 4Q model, taking much of the burden of qualification and validation off of you. 5

6 This ultimately can help you decrease your R&D cycle time and speed up your time-to-market. For example, the PQP includes: Risk Analysis Design (DQ) Installation (IQ) Operational (OQ) Performance (PQ) Traceability Matrix Standard Operating Procedure (SOP) Training is approved, complete, and documented. The final summary report denotes all activities and test points have been completed successfully, and any exceptions have been appropriately resolved. Imagine a year or two or three later, when original validation team members have moved on to other positions. Leaders who approved the many protocols, reports, and change controls have transitioned to other duties. Links and references to documents that once seemed obvious and logical are now gray and difficult to follow. When probing questions arise, and they will, what do you do? The documentation must stand on its own. How is this accomplished? Wouldn t it be great if one document did this? There actually is the traceability matrix. The Importance of Traceability, Personnel Training, and Maintenance The traceability matrix provides a way of linking relevant specifications to test points. It indicates relationships between requirements, tests, and procedures. Not only does this concept easily demonstrate relationships between specifications, risk analysis, IQ/OQ/PQ tests, and the procedures established to maintain the validated state of your instrument, but it can be easily followed by even the most novice individual in the pharma qualification world. If there s one key message to remember about instrument qualification and validation, it s that this is an ongoing process. During inspections, regulators regularly check whether employees are sufficiently trained on the instruments they operate. Unfortunately, employees come and go and so do instruments, which means you re always going to be managing complicated and costly training programs. User training is an integral part of Anton Paar s PQP process. Taking advantage of this component of the PQP can help you save time, reduce overall training costs, and improve compliance over the life of an instrument. An instrument s life cycle is more than commissioning and decommissioning. It is important to recognize that each one of these devices is subject to continuous change control throughout its working life. For example, it may be necessary to add new modules to an instrument to expand its capabilities, or perhaps you have to update its software to work with a new process. Care and maintenance of an instrument thoughout its life cycle via scheduled service checks, calibrations, and safety checks is essential for optimal performance. By partnering with an instrument manufacturer during instrument qualification, you can ensure an instrument will function properly and operate in a regulatory-compliant manner during the course of its life. For example, Anton Paar offers ongoing preventative maintenance, regular maintenance, recalibration, and retrospective qualification of older instruments. The company s qualified service engineers can provide regular checks, calibrations, and adjustments using only certified test equipment. They also can provide emergency repair services. It s not going to get any easier to comply with the bevy of pharma regulations that currently exist or that are on the horizon. But qualifying and validating analytical/lab and process instruments does not have to be as big of a challenge when you partner with your instrument vendor for various services and programs. Table 1: 4Q Model Function Design Installation Operational Performance Activities Compare user requirements with manufacturer specifications; evaluate different manufacturers Verify working environment, check purchased instrument after arrival; check and document installation of hardware/software Test operational functions; conduct performance testing and security settings Test for specific applications, preventative maintenawnce; ongoing performance testing 6

7 The Pharma Package is available for the following instruments Product Group Instruments Density meter DMA 35/500/4100M/4500M/5000M Polarimeter MCP 100/200/300/500 Refractometer Abbemat 200/300/350/500/550/WR/HP Viscometer Lovis 2000 M/ME Microwave synthesis Sample Preparation Rotational Rheometer Masterwave BTR Multiwave PRO RheolabQC Rheometer MCR XX2 Combinations DMA M + Abbemat/HazeQC/Lovis 2000/Xsample 7