ChemisTwin^® Portal FAQ

What is ChemisTwin^® Portal?

ChemisTwin^® portal is an online platform for automated analytical spectra interpretation based on a comprehensive database of digital Reference Materials (dRMs), certified according to ISO9001 and qualified by our NMR scientists. The database includes compounds from our comprehensive product catalogue of Certified Reference Materials (CRMs), and each spectrum is traceable to a physical CRM.

With this portal, users can receive results to confirm or identify their NMR spectra in just seconds. The results are stored in the user’s profile and can be reviewed and shared at any time.

What’s the benefit of an NMR Lab using the portal?

The ChemisTwin^® portal enables the automation and standardization of NMR spectra interpretation. It helps scientists by:

• Reducing the time spent researching literature and weighing materials
• Eliminating the need to source, store, and measure physical reference materials
• Automating spectra interpretation
• Generating reports automatically and storing results for later reference or sharing

I typically use physical Certified Reference Materials. How would I use the ChemisTwin^® portal in my normal workflow?

ChemisTwin^® portal should easily integrate into your workflows. Compared to today's workflow, you now only need to measure and run NMR analysis on the sample substance. You can then use an NMR Data Analysis tool (e.g. TopSpin) to convert the raw spectra data into a .jdx file. Upload the file into the ChemisTwin^® portal, conduct the analysis, and receive results in just seconds.

What types of analyses are supported?

You can perform a qualitative targeted analysis for structure verification or a qualitative non-targeted analysis for identification for any compound that exists in the DRM database. This includes most common small molecules used in pharmaceutical applications for NMR: APIs, Impurities and Excipients, and analytes in the pharmaceutical secondary standards catalog offering.

Quantitative analysis will be available in later releases (estimated 2024).

How difficult is it to use the portal?

ChemisTwin^® portal is an easy-to-use application, and no complex training is needed to get started. Most users have been able to use the tool with no support after 5 – 15-minutes

Are there different user roles?

The ChemisTwin^® portal differentiates between two roles:

Lab Member: Daily user of the ChemisTwin^® portal. A Lab Member can execute and confirm his/her own set of analyses, access the dRM database, and view the web shop.

Lab Administrator: User(s) that act as an administrator within his/her organization’s account. In addition to the Lab Member capabilities, the Lab Admin can view all the analyses for an account and manage users. The portal allows multiple Lab Admins for an account. This may be a Principal Investigator, Lab Scientist, Head of NMR, etc.

How can I sign up for a free trial?

Navigate to the ChemisTwin^® portal page and complete the registration form to sign up for your free trial.

I am interested in the ChemisTwin^® portal, but I am working with other techniques rather than NMR. How can you help me?

Currently, the portal supports Nuclear Magnetic Resonance Spectroscopy (NMR) only. However, the ChemisTwin^® roadmap includes plans for expansion to additional technologies.

Make sure to share your feedback with the ChemisTwin^® team, so they can help you with the estimated timeline for the availability of the portal for your technique.

Which analyses count towards my consumption?

Not counted:

• If you are running a library search and get a “no match” result
• All comparisons with theoretical spectra are not counted.

Counted:

• If you compare your spectra against one or more dRM, it will be counted as one analysis, even if you obtain a "no match" result. This information would still be useful as it indicates that the spectra do not correspond to any of your targeted structures.
• If you run a library search and get one or multiple matches, this is counted as "one analysis".

What is a digital Reference Material (dRM) and how does it differ from a physical Certified Reference Material (CRM)?

When indicated in the portal a digital Reference Material (dRM) can be the digital record of a physical CRM. dRMs are qualified by our NMR scientists according to ISO9001. You can access dRMs through the dRM database in the ChemisTwin^® portal. There is no need for ordering, storing, and weighing like physical reference materials.

How are dRMs created?

Our NMR scientists start by conducting 1H proton NMR of a physical CRM (or RM / Analytical standard when no CRM is available). The resulting spectra and associated measurement data are then reviewed and released under our quality policy. NMR measurements for the dRM production are in accordance with ISO 9001 standards.

What are the experimental conditions for creating the dRMs?

This information can be found within the ChemisTwin^® portal.

• Log in and navigate to the “Search Reference” tab
• Search for the compound of interest
• Select “View DRMs” under the compound name
• Select “View Details”
• See the “Acquisition Parameters” section on the pop-up window

Is it possible to trace a dRM to a physical CRM?

Information on the lot number or batch number of the physical CRM used for creation of the dRM is available in the database when you “View Details” of a DRM.

How many dRMs are available?

We are releasing new dRMs on a weekly basis. You can register with the ChemisTwin^® portal for free and explore the full list of available dRMs there. You can also contact us via email and get the latest list.

Currently, we are focusing on small pharmaceutical compounds, following our pharmaceutical secondary standard portfolio (product part numbers starting with PHR).

Furthermore, you can easily request new dRMs within the portal. The new dRM will be available faster if we have an equivalent catalog product which is in stock, as it will then be easy for us to procure the necessary high quality NMR recordings.

Can I use my own proprietary standards?

Unfortunately, this is not possible in the current release of the ChemisTwin^® portal, but this feature may be developed in future. Contact the ChemisTwin^® core team for additional features of the portal.

What is a theoretical spectrum and how does it differ from a dRM?

Theoretical spectra are produced using the algorithm prediction of a given molecular structure. These spectra are completely built from theory and do not have any traceability to a physical product. They also do not have individual spectra release process like the dRMs. Therefore, their accuracy and reliability are lower than that of dRMs and we recommend confirming the result. This is why we have chosen to give this comparison free of charge to provide you with an alternative in case there is not yet a dRM available for your molecule of interest.

As soon as an equivalent dRM is produced the theoretical spectra will be replaced and you can start benefiting from the full power of the ChemisTwin^® portal.

Currently, there is 60 000 available theoretical spectra in the ChemisTwin^® portal.

How does the algorithm work?

The algorithm generates a predicted spectrum based on the parameters of acquisition (I.e., frequency, solvent, etc.) and compares this to the experimental spectra. The predictions are based on special algorithms (HOSE-codes) and a very large training database containing more than 4 million chemical shifts. The spectra are compared by the difference of chemical shifts and coupling constants, as well as the presence of all expected signals.

How accurate is the algorithm?

AI-powered solutions are as good as the data they are developed on. ChemisTwin^® portal relies on digital Reference Materials and a predictive algorithm that contains more than 4 million chemical shifts from 350,000+ structures. Our spectra database is unique because it has been created and validated by our NMR scientists according to ISO 9001 standards. These data sets are then used by the ChemisTwin^® algorithm for NMR spectra prediction.

The quality of our data results in an unmatched level of quality for our solution.

How long does it take to receive the analysis results?

In most cases, the algorithm will produce results in less than a minute. In rare occasions, the algorithm may require a few more minutes.

While the algorithm runs, you can keep working on ChemisTwin^® portal to add more of your spectra to be analyzed, and you’ll will receive a notification when an analysis is completed and is ready for your review.

Which data formats for NMR spectra does the ChemisTwin^® portal accept?

ChemisTwin^® portal can read NMR raw data in .jdx, .dx, .jdf, .zip or raw Bruker data formats. They can be produced directly by the software piloting your instrument and do not require any additional purchase. Please contact us if you need guidance on how to set your instrument to produce one of these formats or if you need to convert an existing result.

What is the effect if the spectra come from an NMR machine that operates at a different frequency than for the dRMs?

The dRMs are produced from 1H NMR spectra recorded with instruments at 500 and 600 MHz. The strength of the magnetic field affects the chemical shift of the NMR signals. Different magnetic field strengths will cause the resonant frequency of nuclei to shift, resulting in different chemical shifts for the same molecule. The portal can manage the effect of this magnetic field variation and, therefore, compare dRMs to sample spectra measured at a different frequency.

What is the effect if a compound is analyzed in a different solvent than the one used to produce the dRM?

Different solvents have impacts on the chemical shifts of the NMR spectra. The ChemisTwin^® algorithm can predict the solvent effect on the chemical shifts of the spectra. Refer to the acquisition parameters of the dRM to get the most accurate results prior to recording the experimental spectra.

In what range of Hz does the ChemisTwin^® portal accept NMR spectra?

In the range of 300 to 700 MHz.

What is the minimum concentration required for analysis?

The recommended minimum concentration is 0.02 mmol/g. You can also refer to our “How to ChemisTwin” episode 1: How to get good spectra? for full guidance on the NMR data acquisition for best performance.

Will the presence of impurities affect the success of an analysis?

Impurities may affect chemical shifts and include new peaks that overlap with the target compound peaks, affecting the relative integrals. In most cases, the impact should be minimal with impurities lower than 20 %. If impurities are present in greater concentrations, ChemisTwin^® portal might still be able to accurately exclude these peaks and provide a satisfactory result - but depending on the impurities and sample this can lead to questionable or no match results even if you have the correct main structure.

The solvent itself is not considered as an impurity.

What is the effect of moisture content on an analysis?

This can have an impact on the polarity and chemical shifts, but the algorithm can predict this within the tolerance limits.

Can ChemisTwin^® portal identify the compounds within a mixture?

Analysis of complex mixtures will be possible in later releases, in 2024.

What are the subscription options?

You can gain access to ChemisTwin^® portal in the 3 following ways:

Free Trial: A user receives 45 comparisons free of charge during the first 12 months of access. This access offers all the capabilities of the portal but is designed mainly for individual users, such as PhD students.

Pay-per-use: ChemisTwin^® portal charges based on the number of eligible results you have performed in the portal, while comparison with theoretical spectra is entirely free of charge (for details see question 9). Consumption will be managed by pre-paid and post-paid subscriptions.

Pre-paid: When you agree to purchase a pre-set amount of credit that is later translated into number of eligible results in the ChemisTwin^® portal. You can top-up your credit at any time.

Post-paid: When you set a consumption maximum and receive a monthly bill based on the eligible results consumption for that particular month.

Universities are eligible for a specific discounted price, please contact us for more details.

I have a free trial access. How can I convert it to a subscription?

Before the end of the trial, you will receive a communication within the platform with information on subscription models available and how to order.

How do I invite a person to join the DRM portal?

If you are a Lab Admin, you can navigate to User Management and select "Add User". You will need to provide the user email and role to send an invitation to a new user.

A person from my organization cannot log in anymore. What can he/she do?

Make sure that his/her account is not deactivated. In case the issue persists, please contact ChemisTwin^® support here.

A person that I invited did not receive any log in information. Can I re-send the invitation?

Yes, you can re-send the invitation. Go to the user management screen and click the button "Re-send invitation".

Can I use the DRM portal even without a phone number?

A mobile phone number is required for the first registration, then you can choose a 2-factor authentication method that does not require a mobile phone number in your ChemisTwin^® account settings.

On which browsers can the ChemisTwin^® portal be used?

Customers can use any browser to access the ChemisTwin^® portal. For optimal performance, we recommend using Google Chrome. We also do not recommend using the portal in incognito or private browsing mode.

Who can see my analyses?

As a Lab Member, you can only see your own analyses. A Lab Admin can see all analyses that are performed in your Lab.

How does the ChemisTwin^® portal handle data security & data integrity?

Chemistwin usesleverages Amazon AWS cloud services. Amazon is a company certified to comply with ISO 9001, 27001, 27017, and 27018 for this service.

Data in transfer is protected by industry standard TLS encryption.

Data at rest is encrypted with AWS KMS.

Data uploaded is additionally secured through checksums.

Access to the AWS accounts and resources for administrative/operational tasks are tightly controlled by Merck Enterprise IT standards and policies.

How does the ChemisTwin^® portal handle data traceability?

Electronic records are tracked in an audit trail viewable within the ChemisTwin^® portal, and the deletion of records is not allowed.

How do you ensure the platform is secure?

The ChemisTwin^® application development followed a secure software development lifecycle to ensure the fulfillment of application security requirements and the security of the systems and information involved in the development.

What are the regulatory policies that are being followed?

Merck is an ISO 9001 certified company. ISO 9001 is followed for the production of digital Reference Materials (dRMs).

Is the ChemisTwin^® portal GxP compliant?

A GxP compliant portal is targeted for later release. If you are interested in validating ChemisTwin for GMP purposes, lease contact us, as we would like to build a GxP package relevant for you.

The ChemisTwin^® portal is not 21 CFR Part 11 compliant. However, the system has been developed taking 21 CFR part 11 requirements into consideration as we are planning a future version of ChemisTwin^® that will be GxP and 21 CFR Part 11 compliant.

The development of the portal took in consideration of the GAMP 5 industry standards for computerized systems. Privacy and protection of personally identifiable information are ensured.