CIL has state-of-the-art production facilities for cGMP and non-cGMP manufacturing at its locations in Andover and Tewksbury, MA. The company employs over 40 chemists in production, more than half of whom hold higher degrees, with many years of experience exclusively in the synthesis of stable isotope-labeled compounds.
CIL’s chemistry laboratories are equipped with apparatus for both large-scale (50 L and over) and microscale chemistry, including equipment for high-pressure gas reactions, pH and temperature-controlled enzyme chemistry, high-resolution distillation processes, and catalytic reduction with both hydrogen and deuterium. The production laboratories are also equipped with analytical equipment for in-process testing, including GC-FID, GC-ECD and HPLC with UV, RI, ELSD, and MS detectors. Automated separation equipment for preparative scale chromatography on silica gel and resin is also available, as is preparative GC.
The production department has vast experience in taking highly purified labeled materials and preparing high-quality quantitative solutions as analytical standards, either as single-component products or multi-component mixes and calibration solutions. By using procedures that have been carefully developed and refined incorporating many years of experience in the field, the formulated analytical standards meet the most exacting requirements. The department has also prepared analytical standards and calibrators in reconstitutable dried-down formats for over 15 years. Where appropriate, these products are prepared under ISO 13485, ISO/IEC 17025 and ISO Guide 34 quality systems.
CIL's Quality Control Laboratory
The Quality Control laboratory at CIL has a staff of 17 personnel, most with a bachelor's degree or higher. Most have been with the company for ten years or more.
There is a comprehensive quality system in place for analysis of both nonregulated and regulated materials. The quality system covers all aspects of testing, from training of personnel, control of documents, compliance with regulatory requirements, maintenance of equipment, generation of analytical records, general test methods, compound-specific test methods, recording of test results, and handling of out-of-specification results and materials. CIL is routinely audited internally by its QA department and externally by customers, notified bodies, and regulatory agencies (e.g. FDA).
The laboratory handles testing for all of CIL’s products and incoming raw materials, as well as in-process testing for the production laboratories, shelf life and stability studies. The materials range in complexity and physical form, from simple gases (e.g. labeled oxygen) to complex organic molecules like erythromycin. The laboratory is equipped to test and characterize the 15,000 different materials that constitute the CIL inventory and associated intermediates. Tests range in complexity from simple physical and spectroscopic characterization to chromatographic tests for purity, chiralty and mass-spectrometric testing for isotopic enrichment.
The in-house testing capabilities cover GC/MS, GC/FID, GC/ECD, HPLC/UV HPLC/RI HPLC/ELSD HPLC/DA HPLC/Pickering, 1H-NMR, 13C-NMR, multinuclear NMR, wet chem, FTIR, TOC, polarimetery, and KF testing. If the instrumentation required for a test is not available in-house, then the testing is subcontracted out to a qualified vendor.
The laboratory has the personnel and systems in place to develop and validate new analytical methods, as well as to conduct testing according to all major standards. USP/NF and EP compendia methods are regularly used, and other compendia (BP and JP) are used as required.
CIL's cGMP Laboratory
CIL moved into its newly constructed cGMP facility during the spring of 2013. The new facility has five production rooms (one dedicated to the production of 13C-labeled urea (a diagnostic drug for the detection of H. pylori), two dedicated isolation rooms (one dedicated to the production of 13C-labeled urea), a cGMP-dedicated analytical laboratory (QC laboratory, approximately 1,400 square feet), a packaging laboratory and a development lab. CIL has the capability to produce as many as four different cGMP-manufactured clinical trial materials simultaneously (scale: from 0.1 to 10 plus kg). CIL routinely produces eight isotopically labeled compounds for use in clinical trials: L-leucine, mono-labeled 13C sodium acetate, bis-labeled 13C sodium acetate, 6,6-D2-labeled glucose, universally 13C-labeled glucose, 70% deuterium oxide, 13C-labeled sodium pantoprazole and labeled dextromethorphan. In addition, CIL can offer contractual cGMP production of other isotopically labeled (stable isotopes) compounds.
Our cGMP production facility currently has a staff of six full-time, dedicated cGMP-trained scientists, along with a staff of nine cGMP-trained development scientists, who can work in cGMP production to provide rapid turnaround of contract cGMP orders.
Environmental Contaminant Standards
CIL has been making isotopically labeled environmental contaminant standards since its conception over 30 years ago. The original target analytes were well-known “legacy” persistent organic pollutants (POPs): dioxins and furans, PCBs, PAHs and organochlorine pesticides, as well as priority pollutants ranging from chloroform to hexachlorobenzene and beyond. Over the years, as new pesticides came to the attention of toxicologists and regulators, CIL added less-persistent chemical classes, including, but not limited to, organophosphorous, carbamate and pyrethroid pesticides, and CIL was the first to commercially offer brominated flame retardants such as BDEs and HBCDs.
Recently, interest has shifted to areas such as metabolites of both persistent and nonpersistent pesticides, pharmaceutical and personal care products, and the general area of “biomarkers,” all of which benefit from analysis by isotope dilution mass spectrometry (IDMS). CIL now routinely produces individual standards (both isotope labeled and unlabeled or “native”), quantitative mixtures of related compounds and entire sets of calibration solutions. Typically, over 100 new compounds are produced every year, and an equivalent number of mixtures.
ABX - Leaders in PET
ABX is the world’s leading supplier of 18F positron emission tomography (PET) precursors and reagent kits and cassettes, including, but not limited to, kits for FDG, FLT, F-Choline, NaF, F-Miso and FET. Specializing in the manufacture and development of chemicals for nuclear medicine, ABX’s cGMP-approved laboratories, class 100 clean rooms and cGMP radiochemistry development hot lab uniquely position ABX to provide complete PET and SPECT chemistry solutions to radiochemists and radiopharmacists worldwide. ABX’s radiochemistry hot lab is equipped with most of the leading commercial PET tracer synthesis boxes and allows ABX to assist customers with the optimization and development of new tracers.