Compliance Checker A Solution from Pre-Competitive Space

Compliance is important

The penalties for not maintaining compliance are real…

– Large Retail Pharmacy Pays $77 Million Fine

– DEA issues Two Year Suspension for Wholesale Distributor's Ability to Sell Controlled Substances.

– Large Logistics Carrier Pays $40 Million Fine

– Large Retail Pharmacy Chain Pays $80 Million Fine DEA Inquiry

– 2008 ‘Major Pharmaceutical Company’ settles with United States over record keeping of Controlled Substances - $511,000 in fines

– 2009 ‘Pharmaceutical Company’ was contacted by the U. S. Department of Justice representing the Drug Enforcement Administration concerning alleged regulatory violations of the Controlled Substances Act. The company paid a civil fine of $250,000

Source: Pistoia Alliance

Controlled Substances???

Gamma-hydroxybutyric acid

Chloral hydrate Ketamine Amphetamine

Piperonal Acetone

ALL ARE CONTROLLED !!!

Beyond Borders

• Each country’s legislative approach leads to different sets of controlled substances

Salvinorin A Germany but not US

Caffeine Controlled in China

Tramadol Controlled in US + Sweden

Working together with the Pistoia Alliance!

CSCS Milestones :

• 2012 – Project starts

• Early 2013 – RFP published

• April 22, 2013 - Pistoia Alliance have chosen ChemAxon + Patcore to develop Compliance Checker

• End 2013 – UAT testing starts

• March 11, 2014 – UAT approval

– dataset of over 400 chemical structures to challenge the system

– the dataset contained both controlled and non-controlled structures across a range of chemical classes and legislative schedules

– team of experts drawn from major life science organizations

AstraZeneca Bayer GlaxoSmithKline Merck Novartis Roche

What is Compliance Checker?

Text, CAS #, Name, etc.

Compliance Checker pedigree

• Marketed in Japan as CRAIS Checker since 2006 and currently used by 30+ companies

• Powered by JChem’s Markush technology

• Easily integratable

• Supported worldwide by ChemAxon and Patcore

The Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade (PIC)

Substances listed of the Montreal Protocol on Substances that Deplete the Ozone Layer

United Nations Recommendations on the Transport of Dangerous Goods

United Nations Single Convention on Narcotic Drugs 1961

United Nations Convention on Psychotropic Substances 1971

United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances 1988

EU REGULATION (EC) No 273/2004 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 11 February 2004 on drug precursors

US Controlled Substance Act Schedule I-V

US Chemical Diversion and Trafficking Act List I-II Chemicals

CA Controlled Drugs and Substances Act Schedule I-VIII

UK Misuse of Drugs Act Part I Class A-C Drugs

UK The Misuse of Drugs Regulations 2001 Schedule I-IV

IN Narcotic Drugs and Psychotropic Substance Act 1985

CH Swiss Controlled Substances Act (BetmVV-EDI) Narcotics List A-G

FR Arrête du 22 fevrier 1990 fixant la listedes substances classees comme stupefiants ANNEXE I-IV

FR Arrête du 22 fevrier 1990 fixant la liste des substances psychotropes PREMIERE-TROISIEME PARTIE

DE Gesetz uber den Verkehr mit Betaubungsmitteln (Betaubungsmittelgesetz - BtMG) Anlage I-III

DE Gesetz uber den Verkehr mit Arzneimitteln (Arzneimittelgesetz - AMG) Anhang I-III

S Lakemedelsverkets foreskrifter om forteckningar over narkotika Forteckning I-V

IRE MISUSE OF DRUGS REGULATIONS 1988 Schedule I-V

NL Opiumwet 12 mei 1928 Lijst I-II

IT Decreto del Presidente della Repubblica del 9 ottobre 1990, n. 309 TABELLA I-II

BE Arrête royal reglementant les substances soporifiques et stupefiantes, et relatif a la reduction des risques et a l'avis therapeutique

BE Arrête royal reglementant certaines substances psychotropes, et relatif a la reduction des risques et a l'avis therapeutique

DK Bekendtgorelse om euforiserende stoffer Liste A-E

E LEY 17/1.967, DE 8 DE ABRIL LISTA I-IV

E REAL DECRETO 2829/1.977, DE 6 DE OCTUBRE LISTA I-IV

Full Japanese coverage, etc…

Use Cases

Check that… … what you already hold is legal

… what you plan to synthesize is legal

… what you play to buy is legal

… what you plan to ship is legal over there

Departments need Compliance Checker!

… AND know this before new legislation becomes active

Chemical Weapons, A. Costache & K. Niesz, European Biopharmaceutical Review 67: pp70-72, April 2014

Any ester or ether of ---

Any salt of ---

Any stereoisomeric form of ---

>>> UK MDA >>> Schedue II, Part 1, Class A Drugs

Hit

Ether Ester

Potassium salt

Mixture Dimepheptanol

Detects various forms

Detects only regulated structures

Any compound (not being a compound for the time

being specified in sub-paragraph (a) above) structurally

derived from Tryptamine or from a ring-hydroxy

Tryptamine by substitution at the nitrogen atom of a

side-chain with one or more alkyl substituents but no

other substituent;

Any ester or ether of ---

Any salt of ---

Any stereoisomeric form of -

--

>>> UK MDA >>> Schedule II, Part 1, Class A Drugs

Alkyl

Phosphate ester

and

*Over all description for schedule II

Complex controlled substance definitions

Desomorphine

(krokodil) rule for

the UK MDA

Pethidine (Demerol)

rule for the UK MDA

• Poisonous and Deleterious Substances Control Law

• Fire Services Act

Toxic, deleterious and dangerous substances

• Export Trade Control Order

• Law on the Prohibition of Chemical Weapons and the Regulation of Specific Chemicals

• United Nations Recommendations on the Transport of Dangerous Goods

Security

• Industrial Safety and Health Law

• The Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade (PIC)

Safety and health

• Act on Confirmation, etc. of Release Amounts of Specific Chemical Substances in the Environment and Promotion of Improvements to the Management Thereof (PRTR)

• Substances listed of the Montreal Protocol on Substances that Deplete the Ozone Layer

• Agricultural Chemicals Regulation Law

Environment protection

• Unfavorable Substructure

Research Support

Beyond Controlled Substances

SOAP Web Client Windows Client Command Line

Interface for

external systems

(ELN, Inventory,

Registration, etc.)

Batch processing,

Automation,

Pipeline Pilot

KNIME

Quick Check

Batch Check

System administration

Open to everyone

Batch processing

for large SDFs

(library

management)

Compliance Checker Server

Compliance Checker

Useful links: http://www.chemaxon.com/products/compliance-checker/ http://www.pistoiaalliance.org/news_events/in-the-news-24838/489-cscs-vendor-selection.html http://www.pistoiaalliance.org/news_events/press-releases/502-cscs-press-release.html http://edition.pagesuite-professional.co.uk/Launch.aspx?PBID=587773cf-29c4-46f2-9d9d-2f87bf178b5c