The same can be said for the identification and tracking of controlled substances within a compound library. A controlled substance management package is a critical tool for identifying these compounds in a compound library.  

As you must ensure that your practices align with legal requirements for identifying, handling, storing and movement of controlled substances, such an option will provide you with robust governance and accountability for controlled compounds in your inventory. If by any chance such laws, regulations, or ordinance is violated, it may cause the loss of reputation, sales, and can also result in financial and criminal penalties.

Whilst some companies try to maintain their own compliance checker systems, a dedicated system, from external suppliers, gives the user confidence that experts are reviewing, checking and updating compliance packages in a timely manner.  

Our dog in this analogy is Chemaxon’s Compliance Checker, a combination of a software system and a regularly updated content package providing a flexible tool to screen chemical structures efficiently against the controlling legislation.

How would this look in your lab?  

The global nature of life science R&D including outsourcing and collaboration, is a given in today’s pharmaceutical industry, with synthesis, compound management and testing facilities distributed globally and reliant on fast and efficient shipment of compounds across borders to the appropriate testing facilities. This means that you need to not only be aware of the compliance against controlled drug legislation of your in-house library, but also aware of legislation in your partners locations. To put it simply, a package such as Compliance Checker is able to scan a library of around 45 million compounds against all legislation in a weekend.

Additionally, newly synthesised compounds can be scanned against all legislation overnight and all compounds against new legislation again, overnight. The advantage of this is that you are assured your libraries are compliant and can take necessary actions as and when required. It’s also proven to be a useful tool to identify any issues with libraries purchased from outside vendors who may not have such stringent identification packages. Who wants to be purchasing compounds they can’t easily use?

What goes on behind the scenes to keep the products up to date? A team of experts continuously monitor government resources across a range of countries. New regulations are then immediately extracted and automatically merged into the existing knowledge base, meaning you don’t have to do any of the hard work updating internal systems.

So how does this work? Regulations are transformed into chemical query structures (sometimes highly complex Markush structures) that are matched against the substances to be checked. In addition, to comply with the US Controlled Substances Act and the Canadian Controlled Drugs and Substances Act, structurally similar molecules are also detected based on a consensus similarity model, and then categorised as high similar or similar hits.   Compliance Checker has a sophisticated search engine which allows it to check vast numbers of structures against these highly complex Markush structures, without which incomplete results would be obtained. 

Different query features in a Markush structure

What’s so important about these Markush structures and how are they used in legislation?  Markush structures come into their own as we see the rise in generic definitions in controlled drug legislation. These definitions are comprehensive descriptions or classifications that encompass entire groups or classes of compounds based on their chemical structures. The surge in generic legislation coupled with the general increase in laws around controlled substances, makes it imperative that a package which can quickly and easily identify controlled substances, is implemented.  

In the past, controlled compounds were listed on a named basis, for example ‘Cocaine’, which could easily be converted to a structure to be tagged in inventories. This allowed for an easily manageable and clear process for identifying, licensing, and moving compounds around, locally, or world-wide. Now, we are seeing more generic legislation which allows legislative bodies to cover not only known but also all possible variations of a controlled structure in one amendment proactively, rather than being behind the curve ball and legislating after the appearance of the specific structure on the market.

Efficient searching against Markush structures requires advanced methods that go well beyond simple structure-based search. The complex Markush structures resulting from generic definitions present a big challenge for standard search engines. The new query technology of Compliance Checker’s search engine optimises searching capability to process the enormous numbers of potential controlled compounds, as defined by Markush structures, against your compound library. You need both the search engine and the ability to transform regulations to complex Markush structures for conclusive results. The ComplianceChecker search engine is based on a new query technology which has been optimised to process the enormous numbers at great speed.

A good example of generic legislation is the definition created to cover the third generation of synthetic cannabinoids that was set into law as The Misuse of Drugs (Amendment) (England, Wales, and Scotland) Regulations 2016 to the Misuse of Drugs Act (1971). This was a highly complex set of Markush structures and in theory covered 10¹⁰⁵ structures (approximately, and yes that is not an error).

Substructural fragments in JWH-018 that can be replaced in designing synthetic cannabinoids

Near impossible for an internal scientist to name these individually, and an extremely difficult task for an in-house IT group to code, check and deliver in a timely manner. This is where having an external, dedicated resource such as Chemaxon’s Compliance Checker really can make a difference. Their support team were able to turn the written legislation into the required Markush structures and have it ready for implementation on day 1. To run this number of queries, it’s imperative that the system has an efficient and effective search engine as mentioned earlier. 

To re-cap, what happens in the background and how it happens is important, but for a lab user, the overarching question is ‘Am I compliant with legislation today. This is assured because we monitor up-and-coming legislation which means that not only are you always ensured to be compliant but also that new legislation may be run early to predict any future issues you may see in your collection. And thinking back to Markush structures, around 22 countries include generic descriptions in their legislation, with Belgium actually using this idea most widely. It is imperative that these are easily and properly identified in a timely fashion.

What sort of a home do you need for your dog?

Chemaxon has a number of different packages depending on the size of your dog or library.   For large systems, we offer a cloud based SaaS (Software as a Service) package. A cloud based package eliminates the upfront cost of installation, as well as on–going costs like maintenance. It also gives you a quick setup and deployment option that can be updated easily as legislation changes. Seamless automatic upgrades are attractive for small companies, because they may do not have the required IT expertise, and for large enterprises this could be the preferred option because they need a high-performance, cost-effective solution. If you only have a small dog or just walking one now and again for a friend, Chemaxon has both a lite and subscription service available.

Automatic scan of compound collections using the Compliance Checker Integration API

And if you want to have more than a standalone system, as Compliance Checker has a RESTful API, it can be easily integrated into your inventory and registration applications.

So let’s just sum up to clarify how useful your new pet is going to be:

• Fast enough to scan around 45 million compounds against all countries in a weekend. 
• Legislation is monitored and content updated in a timely fashion
• Sophisticated search engine allows checking of millions of compounds against complex Markush structures
• The software can be integrated into existing Registration and Inventory packages
• Compliance Checker is also available as a ‘lite’ package and on a request basis.