Frequently Asked Questions
Question – How many types of NanoRam are there? Which device should I use?
Answer- There are 2 types of NanoRam devices. NanoRam uses a 785nm laser with a TE-regulated CCD for detection, and NanoRam-1064 uses a 1064nm laser with a TE-cooled InGaAs detector for detection. NanoRam has an onboard software NOS operation system, with a PC-based database management system NID. NanoRam-1064 has an onboard software NOS-1064 operation system, with a PC-based database management system NID EX. Both NanoRam units are designed for pharmaceutical raw material identification.
Question – Is the NanoRam Series in line with regulations of the Pharmacopoeia, GMP, PIC/S and FDA?
Answer- The NanoRam series meets the requirements set forth by the USP, European Pharmacopeia, Japanese 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 NanoRam manufactured comply with the new 2016 European Pharmacopeia EP 2.2.48 guidelines, which have specific guidance for handheld Raman. Earlier NanoRam models can be recertified. NanoRam 785 and 1064 also comply with the latest released USP chapters for Raman spectroscopy, <858> and <1858> released in August 2020. The NanoRam series employs the 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 series software (NOS and NID for NanoRam, NOS-1064 and NID EX for NanoRam-1064) is 21 CFR Part 11 compliant, following the detailed guideline in 11.10 Controls for closed systems, 11.50 signature manifestations, 11.70 Signature/record linking, 11.200 Electronic signature components and controls and 11.300 Controls for identification codes/passwords.
Question– Does the NanoRam series have a library, and how many signatures are available?
Answer– The B&W Tek NanoRam and NanoRam-1064 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 must be validated by the user if it is to be used for GMP product release.
Question– Can I use a third-party library for GMP product release? What about validated libraries?
Answer– It is very important to know that spectral libraries are not generally considered an approved means of material 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 NanoRam-1064 software identification mode is based on a patented RVM multivariate method with a minimum of 5 scans per material, and has an onboard method validation procedure. The validated method gives a Pass/Fail result with a statistical confidence, thus is more suited for materials identification and acceptance testing.
Question– What capability of library building does NanoRam offer?
Answer– The NanoRam series software offers the capability for easy integration of new materials or compounds with the ability to create and validate new libraries. NanoRam users can easily 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.
Question-Does the NanoRam series allow me to verify the identity of my material such that I can accept the material as meeting specifications?
Answer– The NanoRam series provides robust algorithms for identification and verification of samples. The p-value from a multivariate method on the NanoRam (both 785 and 1064) 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.
Question– Can I identify different components in a formulation blend or mixed product?
Answer– NanoRam series include mixture analysis capabilities to identify multiple components in a sample for investigation purposes.
Question– What is the data storage capacity on the NanoRam series?
Answer– Both NanoRam and NanoRam-1064 are equipped with a 12GB internal SD card, which is mainly used for data backup purposes. The internal storage 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 series for incoming raw material analysis?
Answer– ROI from the NanoRam can be broken down into the following categories:
1. Facilities reduction: The NanoRam/NanoRam-1064 can be used to rapidly identify samples in the loading dock, warehouse or lab, helping to eliminate sampling and quarantine areas.
2. Faster sampling: Since measurements can be made directly through many transparent packaging materials, this removes the need for taking samples from incoming containers, and reduces the need for solvents and consumables. Thus, personnel do not need to contact 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.
3. 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.
4. 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 series 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– Are the libraries and accessories included in the list price?
Answer– The NanoRam and NanoRam-1064 are sold with a comprehensive set of accessories and the USP library is included in the standard package.
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. The NanoRam-1064 uses a 1064nm laser with a maximum power output of 420mW. These are class 3B laser light sources and comply with 21 CFR 1040.10, Laser and Laser Systems. Both systems are 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 power adjustable?
Answer– For NanoRam series, the laser power is easily adjustable from 10% to 100% maximum power in 10% increments via software.
Question– What is the working distance of measurement for both NanoRam and NanoRam-1064?
Answer– For the point and shoot adaptor, immersion probe and the right angle adaptor, 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 5 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 785?
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 resulting 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– 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. A method on the NanoRam-1064 can take less than 5 minutes to create, as it only requires a minimum of 5 scans per material. 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. 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– 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 brown paper or kraft paper bags?
Answer– It’s generally not recommended to identify raw materials directly through opaque packaging, considering the change of packaging could also affect the potential pass/fail result. However, NanoRam-1064 is compatible with our Large spot adaptor (TID-STA) which gives a deeper penetration depth into the packaging. This combination can be used to develop possible applications of raw material identification through paper bags.
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 satisfactory results, but it is always best to test the containers for the ability to produce positive results. The B&W Tek applications team will be glad to share past successful implementations and provide assistance for method development.
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– Handheld Raman is more suited for effective surface measurements. Excipients become part of the analysis and, as long as they are Raman active, will contribute to the measured Raman spectrum, 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. Contact BW Tek for advice on other suitable devices such as QTRam for tablet related applications.
Performance and Maintenance
Question– How do I know my NanoRam series device is performing well?
Answer– The performance test ensures the instrument meets the requirements as set forth in pharmacopeias for handheld Raman used for qualitative analysis. 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– 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 device comes with a polystyrene validation standard for performance verification of the instrument at any time. The NanoRam (both 785 and 1064) 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– Does the NanoRam series 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. The NanoRam-1064 also comes with 2 rechargeable batteries, allowing worry-free continuous operations.
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 all NanoRam Product. 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– What is the lifetime of the laser source?
Answer– For both NanoRam and NanoRam-1064, the laser source has a typical MTBF (mean time before failure) of over 10,000 hours of use time.
Question– Is the NanoRam dustproof and water tight?
Answer– The NanoRam has an IP64 rating. The NanoRam-1064 has an IP65 rating. This means that both are protected from the ingression of dust and water splashed on it from any direction. For IP68 rated NanoRam-1064, please contact B&W Tek directly.
Question– How do I clean my instrument?
Answer– A NanoRam series instrument 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– Does the NanoRam have an internal ID?
Answer– Each NanoRam and NanoRam-1064 has a unique serial number that is registered in the firmware and traced with each measurement. Each scan also has a unique scan index, and together with the unit serial number ensures data traceability.
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 the user modify the standard report features and customize them to fit corporate formats and, if so, how can this be achieved?
Answer– The NanoRam (both 785 and 1064) supplies users with software to store, 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.
Question– Can I delete the data or record if I am not satisfied with it?
Answer– Data on the NanoRam and NanoRam-1064 cannot be deleted, due to potential violations of 21 CFR Part 11 regulation. All result files are kept and can be managed in the NID software loaded on a PC.
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. NanoRam-1064 data can be managed and viewed on a PC from the NID EX software. The data can be further exported from NID/NID EX in .txt, .csv and .spc formats for use in other data viewing and analysis software such as BWID, BWIQ and BWSpec.
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.