2012/2013 Version: December 31, 2012 Steroid Analytical Reference Standards and Drug Impurities Dalton Pharma Services: A Health Canada Approved Facility Level-8 Controlled Substances License on-site SCC Approved GLP Facility North American Manufactured and Shipped To Order Call: 1.800.567.5060 To Order Call: 416.661.2102 Email: [email protected] Email: [email protected] Page 2 Dalton Standards and Impurities Table of Contents Introduction/Company Profile 4 Custom Synthesis Overview 6 Contract Research/Medicinal Chemistry 7 Process Development Overview 8 Analytical Services 9 GMP API & Sterile Filling Services 11 Formulation Development Overview 12 Liposomes 13 Dalton Standards and Impurities 14 Establishment License 16 Certificate example 17 Steroids 18 Page 3 To Order Call: 1.800.567.5060 To Order Email: [email protected] Call: Company Profile About Dalton Pharma Services Dalton Pharma Services is a privately-held pharmaceutical services company that has been producing Fine Chemi- cals on a custom basis for research and chemical supply houses for over twenty-five years (Fluka, Aldrich, Sigma, Acros). We have identified and supplied many new re- agents for biological and pharmaceutical applications, this includes novel analogues and impurities of active pharma- ceuticals ingredients, as well as new linkers. We are lead- ers in process development, process improvement, and in the field of isolation of kilo quantities of biologically active molecules from natural sources. Dalton excels at advancing projects from R&D into GMP environments for its customers. With the ability to manufacture cGMP API's from bench scales to multi kilos we can meet most clinical and small scale commercial requirements. We also offer the rare ability to produce sterile APIs for aseptic processing in our sterile suites. We pride ourselves on being able to reliably deliver an integrated full service offering all the way from discovery support to the production of sterile injectable finished doses. We continue to add to diverse catalog of compounds available from our inventory of standards and impurities. All of our high quality compounds are manufactured and shipped from our North Ameri- can facilities directly to you. We serve a diverse group of customers including private and public laboratories, research institutes, university research labs, clinical research organizations, pharmaceutical manufacturers, analytical testing laboratories and many more. Our staff bring years of experience as synthetic organic chemists and have a proven ability to effi- ciently manage a wide variety of complex chemistry and biotechnology projects. To place an order: Website: www.dalton.com. Email: [email protected]@dalton.com. Phone: (8 am — 5 pm EST) 1.800.567.5060 (Canada/US) +1.416.661.2102 Fax: +1.416.661.2108 Page 4 Dalton Standards and Impurities Company Profile • 42,000 sq ft facility in the Greater Toronto • Over 60 employees: Area • 25 at Ph.D. / M.Sc. level • Adjacent to Toronto’s York University • cGMP API manufacturing suites • Close proximity to Toronto area pharma, • Health Canada/EU Approved Site biotech, medical research facilities • Analytical laboratory • Secure, controlled environment • Research library • Integrated synthesis laboratories • cGMP Sterile injectable manufacturing • Solid encapsulation production Our Services • cGMP API Synthesis • Contract Research • Sterile Filling • Custom Synthesis • Formulation Development • Process Development • Stability Studies • Medicinal Chemistry • Conjugation Chemistry • Contract Analysis • Commercial Manufacturing Page 5 To Order Call: 1.800.567.5060 To Order Email: [email protected] Call: Custom Synthesis Services Our Strength is Chemistry Extensive Experience across a wide range of structural classes Custom synthesis of small molecules and fine chemicals is central to small molecule screening and small molecule drug development. Operating under GLP, cGMP or non-GMP conditions and utilizing reactors up to 100 L, we specialize in the custom synthesis of a wide range of small molecules in- cluding active pharmaceutical ingredients, pharmaceutical intermediates, drug intermediates, drug metabolites, drug analogs, analytical standards, reference standards and certified reference materi- als, chemical intermediates, chemical standards, and pharmaceutical impurities. Proprietary information and IP rights are fully respected Page 6 Dalton Standards and Impurities Contract Research Services • Our chemists become an extension of your own resources • Process optimization / route development / scale-up / synthetic feasibility • “Rent-a-chemist” or “Fee-for-service” models • Legal cases / expert witness Medicinal Chemistry Services • We identify new chemical entities for your drug discovery / development program • Can perform either hit-to-lead identification or drug optimization services • Flexible deal structures (Straight FTE or FTE with milestones / royalties) Page 7 To Order Call: 1.800.567.5060 To Order Email: [email protected] Call: Process Development & Scale-Up Services Our extensive experience in synthetic organic chemistry, including complex chemistry, chiral compounds, hydrogenation, natural products chemistry, organometallic chemis- try, nucleotide and amino acid production, stable isotope synthesis, fluorescent probes, and inert atmosphere chemistry, and our ability to work with most drug classes includ- ing Steroids, Opioids and Cannabinoids, al- lows us to deliver highly specialized outputs meeting the needs of our customers. We ex- cel in process development, process im- provement, and in the field of isolation of kilo quantities of biologically active molecules from natural sources. In addition, Dalton’s custom synthesis department is supported by a full analytical chemistry laboratory (MS, NMR, HPLC, FTIR, LC/MS, Karl Fisher, etc.). Dalton's chemists enjoy being challenged by difficult chemistry problems and look for- ward to solving them. We stand by our products, which are manufactured to the highest quality standards. Page 8 Dalton Standards and Impurities Contract Analytical Services We have built high quality in-house analytical laboratory capabilities to support the development and manufacture what we make as well as for stand alone analytical testing. We also prepare and qualify pharmaceutical analogues, cold isotopic labeling for Metabolites, drug impuri- ties analytical standards, reference standards, and pollut- ant impurity standards in our laboratories for purchase. Our contract analytical lab services include: • Analytical Chemistry Services • Analytical Development Services • Accelerated Stability Services • Microbiology Services Our Contract Analytical Testing Laboratory has a high level of expertise in analytical method development, optimiza- tion, and validation for both synthetic organic compounds and for natural products. Our Analytical Chemistry Depart- ment has established a variety of analytical techniques and our laboratories have the following analytical services capabilities and instrumentation: • Liquid chromatography mass spectrometry LCQ Classic, LCQ Duo with Electrospray Ionizer (ESI), LCQ Deca • HPLC Diode-array UV, variable wavelength UV, conductivity detection and evaporative light scattering detection (ELSD) • GC Flame ionization (FID) and thermal conductivity detec- tion (TCD) and headspace techniques (USP-OVI) • Spectroscopy UV / Visible, Infrared (FTIR), LC-MS, Nuclear Magnetic Resonance (NMR) • Mastersizer 2000 • Polarimeter • Oxygen Headspace Analyzer • Differential Scanning Calorimetry (DSC) Page 9 To Order Call: 1.800.567.5060 To Order Email: [email protected] Call: Analytical Services • Pharmaceuticals & Biopharmaceuticals • Small Molecules • Botanicals & Herbs (NHPs) • cGMP, GLP-compliant • Health Canada License for drug testing • Complete Documentation for Regulatory submissions in the US and Canada • Highly controlled quality systems • Validation to ICH guidelines • State-of-the-art instrumentation • Quality audits are welcome • SCC cerification Analytical Development Dalton develops analytical methods and validates them for drug substance as well as drug product. We fully characterize your molecule and develop robust analytical methods that help ensure the quality of the products we produce and test. • Method Qualifications • Stability Indicating Assays (Stress Degradation Studies) • Assay and Impurity Validations • Product characterization • In-process, bulk and drug product release testing Tailored to meet your specific needs and timelines Page 10 Dalton Standards and Impurities • Gram / kilo / multi-kilo scales • Small molecules & peptides • 3 cGMP suites • Strict environmental & regulatory control • PC, Phase I, II, III, and commercial production • Sterile Vials and Pre-Filled Syringes • Sterile powder fills cGMP Active Pharmaceutical Ingredient (API) Manufacturing Services With a cGMP API manufacturing facility, Dalton can support the Drug Discovery process through API Synthesis for all the stages of clinical trials. We conduct cGMP manufacturing of API's from bench scale to multi kilos and offer sterile production of APIs to support aseptic requirements. Sterile Dose Manufacturing Dalton’s GMP Aseptic Filling capabilities include aseptic filling of liquid-in-vial injectable drugs and terminally sterilized liquid products. Dalton can also produce sterile pre-filled syringe products from clinical to small com- mercial scale. Our sterile filling facilities include two sterile vial filling lines and one syringe filler to meet our customers