Frequently Asked Questions
Question – Is the NanoRam compatible with regulations of the Pharmacopoeia, GMP, PIC/S and FDA?
Answer- The NanoRam meets the requirements set forth by the USP, European Pharmacopeia, and the Chinese Pharmacopeia for Raman spectroscopy. Raman spectroscopy and the NanoRam are recognized as tools that can be used in support of raw material testing and for real-time product release as set forth by the European Medicines Agency. Since April 2016, all new NanoRams manufactured comply with the new 2016 European Pharmacopeia EP 2.2.48 guidelines, which have specific guidance for handheld Raman. Earlier NanoRams models can be recertified. The NanoRam employs a well-recognized Raman method for compliance with the PIC/S & EU GMP guidelines regarding 100% identity assurance for each container of starting materials.
Question- Is the NanoRam software 21 CFR part 11 compliant?
Answer- Yes the NanoRam System (NOS and NID) has a full audit trail and different levels of user access, all of which are password protected with alpha numeric passwords, following the 21 CFR part 11 requirements. Please refer to our 21 CFR Part 11 compliance statement for more details.
Question – Does the NanoRam have an “intrinsic” battery?
Answer – Yes, a rechargeable Lithium Ion battery is installed in the instrument with the power capacity for a minimum of 4 hours of continuous use. Standard operation allows for the instrument to be used for longer periods due to the standard system standby mode feature which, after a few minutes, makes the instrument idle without losing data or the operation point within the software. Therefore, under normal circumstances, one charge of the battery can last a full production shift. For even longer usage times, B&W Tek also offers charging cradles and extra batteries for purchase.
Question – What is the battery lifetime and how easily can a battery be replaced?
Answer- If the battery is not fully discharged each time, the number of cycles available over the lifetime of the product will increase. Generally speaking, the battery can last about 2-3 years. The Lithium Ion battery is an industrial standard battery. A replacement battery (part no. 840000290) as well as a charging cradle (part no. 840000294) can be purchased for the NanoRam. In order to replace the battery, you simply have to open the battery door, pull the old battery out, replace it with the new one and close the battery door to secure it.
Question – Does the NanoRam have a library, and how many components are available?
Answer – The B&W Tek NanoRam comes standard with a library of 110 USP standard pharmaceutical materials, including Active Pharmaceutical Ingredients (APIs) as well as some of the most common excipients and fillers. This library is intended for investigation purposes and it is not recommended to use for GMP quality release. The NanoRam software offers the capability for easy integration of new materials or compounds with the ability to create new libraries. Additionally, the NanoRam provides secure Wi-Fi and Ethernet synchronization capabilities with network terminals in order to optimize time and resources. NanoRam OS is capable of data and report transfers in order to centralize information (such as libraries, methods and final reports) in general servers. As such, it is easy for NanoRam users to add more spectra from their proprietary materials or compounds and then synchronize and transfer the newly added Raman signatures into the libraries of other NanoRams within their network.
It is very important to know that spectral libraries are not generally considered an approved means of materials identification to meet regulatory requirements, but can be helpful for investigation reference of unknown materials. Third party libraries do not provide full traceability of materials and spectra for GMP users, who are required to validate the libraries if they are to be used for material acceptance. The NanoRam software Identification mode is based on a multivariate method comprised of a minimum of 20 scans per material. The validated method can then be used for materials identification and acceptance testing.
Question – Does the NanoRam allow me to verify the identity of my material such that I can accept the material as meeting specifications?
Answer – The NanoRam provides robust algorithms for identification and verification of samples. The p-value from a multivariate method on the NanoRam is the best way to verify materials. These robust methods are based on multiple sample spectra, thus providing representative sampling of multiple samples/lots of material and reflect the natural material variation. It also includes mixture analysis capabilities to identify multiple components in a sample for investigation purposes.
Question – What is the data storage capacity on the NanoRam?
Answer– The internal flash memory on the NanoRam is large enough for general use purposes. Once data have been synchronized to the customer server via the NID software on the PC, the space on the flash RAM is freed for further storage. It is recommended that users regularly synchronize their data from their handheld unit to their data server via the NID software to ensure timely data reporting, data security and to avoid the remote possibility of reaching the maximum data storage limit. Storage varies based on usage, but even with hundreds of methods stored, thousands of measurement results (including their respective original spectral data) can be safely stored on the handheld device. The NanoRam will display reminder messages in the unlikely situation where memory use is approaching its maximum capacity to allow the users the opportunity to sync the data and free up the memory.
Question – What is the anticipated ROI (return on investment) from using the NanoRam for incoming raw material analysis?
Answer – ROI from the NanoRam can be broken down into the following categories:
- Facilities reduction: The NanoRam can be used to rapidly identify samples in the loading dock, warehouse or lab, helping to eliminate sampling and quarantine areas.
- Faster sampling: Since measurements can be made directly through many transparent packaging materials, this removes the need for taking samples from incoming containers. Thus, personnel do not come in contact with the actual materials, reducing the possibility of contamination and improving safety by reducing direct exposure to chemicals. This also means that no product is wasted for testing.
- Time savings: Compared to the traditional methods that require 2 or 3 days to pass through central lab testing and approval processes while the materials sit in the quarantine area, the same process can be completed in approximately 8 hours by using the NanoRam directly in the quarantine area, allowing for materials to be accepted for use quickly without the need to transport them to a laboratory.
- Monetary savings: By using the NanoRam in place of the central lab processing and the expensive equipment and highly-technical labor used in the central lab from the traditional workflow, the cost per sample analysis drops from approximately $14/sample to $4/sample, and space is freed up from the original quarantine area for better use.
Question – What is the standard warranty period?
Answer – The standard warranty for the NanoRam is two years. An extended warranty or an additional certification service plan can also be purchased separately. Extended warranty and service plans can ensure that your NanoRam will perform at an optimum level for many years to come while offering the benefit of factory monitoring and maintenance of the instrument. These types of warranty and service plans can extend the life of the instrument to ensure maximization of the return on investment.
Question – Can the user modify the standard report features on the NanoRam and customize them to fit corporate formats and, if so, how can this be achieved?
Answer – The NanoRam supplies users with software that is able to generate and report data. All data is compliant with 21 CFR Part 11 guidelines and is generated with an audit trail in the instrument operating software and the PC data management and reporting software. The PC software report format can be adjusted according to each user’s specific requirements to comply with corporate reporting formats. Users are able to develop new methods, formats, and display information on the NanoRam.
Question – Are the libraries and accessories included in the list price?
Answer – The NanoRam is sold with a comprehensive set of accessories and the USP library comes standard in the base price. The base package includes: the NanoRam with NanoRam OS software, a power charger, multiple sampling accessories (immersion probe, point and shoot, vial holder, and a bottle adaptor), laser safety goggles, a flash drive with NanoRam ID software, a user manual and quick start guide, a box of vials, a polystyrene validation cap for system verification and routine instrument performance checks, and a carrying case. Other accessories and products that complement the use of the product include additional accessories (tablet holder, right angle adaptor), extended service plans, extended warranty plans, training, validation support, method development support, and annual system recertification.
Question - Does the NanoRam have an internal ID?
Answer – Each NanoRam has a unique serial number that is registered in the firmware and traced with each measurement. This unique ID cannot be altered by the user and the ID number will be associated with all the spectra acquired with that unit, ensuring data traceability.
Question- What kind of laser is used in the NanoRam and what type of safety precautions must be taken?
Answer- The NanoRam uses a 785nm laser with a maximum power output of 300 mW. This is a class 3B laser light source and complies with 21 CFR 1040.10, Laser and Laser Systems. The system is designed with compliant laser safety measures including a soft key switch, a remote interlock, an emergency laser stop key button and proper labels. Laser safety goggles are also provided. Proper laser hazard and safety training is advised.
Question – Is the laser in the NanoRam adjustable?
Answer – The NanoRam uses a 785nm laser with a maximum power output of 300 mW. The laser power is easily adjustable from 10% to 100% maximum power in 10% increments.
Question – What is the maximum poly bag thickness that the NanoRam can measure through? Sometimes the APIs are delivered with two bags. What then?
Answer – The penetrative depth of the laser is about 1-4 mm depending on the actual materials the laser must pass through. It is always best to test the containers and packaging prior to developing a method for testing the delivered materials, as the thickness and material of the pack may contribute to the spectra.
Question – Can the NanoRam “see” through black or dark colored polybags?
Answer - It is typically difficult for Raman spectra to be collected through non-transparent packaging. Some tests through dark polybags have shown positive results, but it is always best to test the containers for the ability to produce positive results. The B&W Tek applications support team will be glad to provide specific development service and share successful implementation information.
Question – While analyzing samples in glass or plastic ampoules, can the NanoRam see the active ingredients inside? Will the presence of water impact the results?
Answer - Raman spectroscopy can “see” through water and most glass and plastic. Therefore, there is no issue when there is sufficient concentration of the active ingredients. The identification of the API will depend on the concentration of the API in the mix of chemicals, its Raman “signal”, and the other chemicals present. The working distance of the NanoRam is several millimeters, depending on which sampling accessory is used, so it can measure through different thicknesses of transparent plastic and glass. Of course, case by case tests are recommended to provide complete and accurate data.
Question – When finished products, like tablets, are analyzed for the identification of active ingredients, will the excipients or coating material interfere with the results?
Answer – Raman is more suited for effective surface measurements. Excipients become part of the analysis and, as long as they are Raman active, will give a reading when measured, along with the active ingredients. When there are coatings involved, issues such as the coating thickness could affect the ability to get a Raman signature of the materials inside the coating. It is always best to test the capsules or tablets to see if they are Raman active. One common method for measuring tablets whose coating interferes with the signal is to cleave the tablet in half and measure the tablet center to minimize potential interference.
Question – Is there any other set of standards required for validation apart from polystyrene?
Answer – There are 8 recognized standards for Raman shift calibration of Raman spectrometers (ASTM E-1840), including naphthalene, cyclohexane, sulfur, 4-acetamenolphenol, and polystyrene. These materials can be used for calibration verification and validation of the instrument. At the time of manufacturing, each NanoRam passes multiple calibration and certification standards set forth by various standard guidelines such as ASTM, USP and EP. Each NanoRams come with a polystyrene validation standard for performance verification of the instrument at any time. The NanoRam software has the capability to measure and store additional performance validation files.
Question – What is the frequency for standard recalibration as per ASTM or NIST?
Answer – Each industry should follow the SOP (standard operating procedure) which fits best with its needs and regulations. B&W Tek recommends an annual system recertification on the NanoRam and that the user runs a performance qualification (PQ) at regular intervals.
Question – What is the lifetime of the laser source?
Answer – The laser source has a typical MTBF (mean time before failure) of over 10,000 hours of use time.
Question – Must the NanoRam be used with a purchased spectral library or can custom libraries be developed?
Answer – The NanoRam includes a library of 110 USP materials. Using the NanoRam, many library items and their methods can be developed within minutes. This allows the users to build their own library and procedures that are traceable to their own standards and can be validated. There is total flexibility for the users regarding the development and management of the library and identification methods. GMP users are required to validate third-party libraries for material quality release. Such users must develop and validate their own spectral libraries.
Question – How long does it take to create an identification method on the NanoRam?
Answer- In most cases, a method on the NanoRam takes less than 10 minutes to create. It requires a minimum of 20 scans per material such that the method is representative of the natural material variability. To ensure a robust method with the best performance, each scan is correlated with previous scans and those with low HQI are flagged, allowing a user to reject scans. After 20 scans are accepted, a multivariate model is created, and the method is complete. The limits of the model are set at 95% confidence based on the spectral data. From this, a default p-value of 0.05 is set as the “pass” criterion for any new samples. A method can be edited to include additional scans, and the significance level can be adjusted during method development. Methods should be validated before use.
Question - Is the NanoRam dustproof and water tight?
Answer- The NanoRam has an IP64 rating. This means that it is protected from the ingression of dust and water splashed on it from any direction.
Question- How do I know whether my NanoRam is performing well?
Answer- To ensure continued system performance, it is recommended that users regularly run a validation check using the provided polystyrene validation cap or another suitable calibration standard. In just a few minutes, a performance validation report is created. The system validation results are included with all test results. System performance is recommended to be certified through annual certification service.
Question- How do I clean my instrument?
Answer- The NanoRam requires minimal maintenance and care. In order to clean the NanoRam touchscreen, wipe it using a soft cloth with ethanol or isopropanol. The main body of unit may be wiped down with water, and plastic surfaces may be cleaned with soap and water. Use ethanol to clean the emission shaft. The rubber jacket may be cleaned with any of the above. Do not use chlorinated cleaning products on any part of the unit. Complete instructions are given in the User Manual and Maintenance Guide.
Question- Can I delete the data or record if I am not satisfied with it?
Answer- Data from tests run in Identification and Investigation mode cannot be deleted from the NanoRam. All result files are kept and can be managed in the NID software loaded on a PC. Sample spectra can be deleted from a library after a note has been entered. All deletions will be entered in the audit trail. Likewise, a method may be deleted by an Administrator or developer-level user only after a reason has been entered; this action will also be recorded in the audit trail.
Question- Can I view and export my spectral data from the NanoRam?
Answer- NanoRam data can be managed and viewed from the NID software installed on a PC. The data can be further exported from NID in .txt, .csv and .spc formats for use in other data viewing and analysis software such as BWID, BWIQ and BWSpec.
Question – What is the working distance of measurement using the NanoRam?
Answer- For the point and shoot and the right angle adaptor on the NanoRam, the focal point is right at the edge of the adaptor. The focal point for the vial holder is roughly 4-5 mm and at the center of the vial. The bottle adapter has roughly a 6 mm working distance. There is also an optional shaft with a working distance of 10 mm available to make measurements through thicker packaging of bottles.
Question – What are the advantages of the temperature controlled and cooled laser and CCD detector that are used in the NanoRam?
Answer – The NanoRam uses state-of -the-art solid state cooling technology to cool and maintain the temperature of the sensor and laser making it more stable, more consistent and more accurate and the resulted spectra less noisy, enabling longer acquisition time for weaker Raman active materials under various environmental conditions such as humidity and temperature variation. The benefit of this increased sensitivity and accuracy is that the NanoRam is more precise and stable.
Question – Does the NanoRam provide individual reports for each measurement?
Answer – Analysis results from the NanoRam are displayed on the unit. Full reports with details including any user-entered notes are generated in the PC-based NID software following synchronization of the unit via Wi-Fi or Ethernet. Summary reports are also available.
Question – Can I have my NanoRam results sent to my LIMS system?
Answer – On synchronization of results for the NanoRam to the NID software, the results including the Raman signature data can also be exported in a LIMS-compatible format.