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1 ? HOW DO YOU TROUBLESHOOT A CHALLENGING METHOD? HOW DO YOU PERFORM A STUDY THAT HAS NEVER BEEN DONE? HOW DO YOU ADJUST A FORM D RELEASE? HOW DO YOU MAKE A DRUG IS ABUSE-DETERRENT? HOW DO YOU MAKE A METHOD MORE ROBUST? HOW DO YOU ENSURE A LINKER WON T BE W DO YOU GET A CLEARER SUPERNATANT? HOW DO YOU MONITOR ANALYTE CONCENTRATION OVER TIME? HOW DO YOU ADDRESS AN FDA RESPONSE LE OU KEEP GENERIC UP WITH PHARMACEUTICALS CHANGING REGULATIONS? RLD REVERSE HOW ENGINEERING DO YOU PREDICT FOR Q1/Q2 EFFECTS EQUIVALENCY OF POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU EVALUATE CONTA TEMS? HOW DO WE MAKE PACKAGING SAFER? HOW DO WE SPEED UP INNOVATION? HOW DO YOU GET A METHOD TO PERFORM AS EXPECTED? HOW DO YO G IS DISTRIBUTED IN A PATCH? HOW DO YOU MEASURE SURFACE ROUGHNESS? HOW DO YOU PREPARE A SCIENTIFICALLY SUPPORTED DEFENSE? HOW DO T A CHALLENGING METHOD? HOW DO YOU PERFORM A STUDY THAT HAS NEVER BEEN DONE? HOW DO YOU ADJUST A FORMULATION FOR TIMED RELEASE? A DRUG IS ABUSE-DETERRENT? HOW DO YOU MAKE A METHOD MORE ROBUST? HOW DO YOU ENSURE A LINKER WON T BECOME TOXIC? HOW DO YOU GET TANT? HOW DO YOU MONITOR ANALYTE CONCENTRATION OVER TIME? HOW DO YOU ADDRESS AN FDA RESPONSE LETTER ASAP? HOW DO YOU KEEP UP W OU COMPLY WITH <USP 232/233>? HOW DO YOU KNOW WHEN TO CONDUCT E/L STUDIES? HOW DO YOU FULLY CHARACTERIZE AN ANTIBODY DRUG CONJU ONITOR CHARGE VARIANTS AND DEGRADATIONS? HOW DO YOU DETECT POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU RE-OPTIMIZE AN ELISA MET T LOT CHANGES? HOW DO YOU IDENTIFY UNKNOWN METABOLITES? HOW DO YOU OPTIMIZE AN ANALYTICAL METHOD UNDER GMP? HOW DO YOU KNOW IF ILAR ENOUGH? HOW DO YOU KNOW RAW MATERIALS ARE PURE? HOW DO YOU EVALUATE PRODUCT PACKAGING? HOW DO YOU IDENTIFY THE SOURCE OF W DO YOU KNOW WHAT ANALYTICAL TECHNIQUE TO USE? HOW DO YOU SIMULTANEOUSLY TEST FOR TWO BYPRODUCTS? HOW DO YOU CHARACTERIZE AN U OU EVALUATE STABILITY IN HOT, HUMID ENVIRONMENTS? HOW DO YOU KNOW RAW MATERIALS ARE PURE? HOW DO YOU KNOW IF A BIOSIMILAR IS SIMILAR OU IDENTIFY UNKNOWN METABOLITES? HOW DO YOU OPTIMIZE AN ANALYTICAL METHOD UNDER GMP? HOW DO YOU RE-OPTIMIZE AN ELISA METHOD WHE CHANGES? HOW DO YOU DETECT POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU MONITOR CHARGE VARIANTS AND DEGRADATIONS? HOW DO YOU P 232/233>? HOW DO YOU KNOW WHEN TO CONDUCT E/L STUDIES? HOW DO YOU FULLY CHARACTERIZE AN ANTIBODY DRUG CONJUGATE? HOW DO YOU M ARIANTS AND DEGRADATIONS? HOW DO YOU DETECT POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU RE-OPTIMIZE AN ELISA METHOD WHEN A REA? HOW DO YOU IDENTIFY UNKNOWN METABOLITES? HOW DO YOU OPTIMIZE GET GENERIC AN ANALYTICAL DRUGS TO METHOD MARKET UNDER SMARTER, GMP? FASTER HOW DO AND YOU WITH KNOW LESS IF A BIOSIMILAR RISK? IS HOW DO YOU KNOW RAW MATERIALS ARE PURE? HOW DO YOU EVALUATE PRODUCT PACKAGING? HOW DO YOU IDENTIFY THE SOURCE OF CONTAMINATION WHAT ANALYTICAL TECHNIQUE TO USE? HOW DO YOU SIMULTANEOUSLY TEST FOR TWO BYPRODUCTS? HOW DO YOU CHARACTERIZE AN UNKNOWN? HOW STABILITY IN HOT, HUMID ENVIRONMENTS? HOW DO YOU KNOW RAW MATERIALS ARE PURE? HOW DO YOU KNOW IF A BIOSIMILAR IS SIMILAR ENOUGH? H UNKNOWN METABOLITES? HOW DO YOU OPTIMIZE AN ANALYTICAL METHOD UNDER GMP? HOW DO YOU RE-OPTIMIZE AN ELISA METHOD WHEN A REAGENT DO YOU DETECT POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU MONITOR CHARGE VARIANTS AND DEGRADATIONS? HOW DO YOU COMPLY WITH <U? HOW DO YOU KNOW WHEN TO CONDUCT E/L STUDIES? HOW DO YOU FULLY CHARACTERIZE AN ANTIBODY DRUG CONJUGATE? HOW DO YOU MONITOR CH DEGRADATIONS? HOW DO YOU DETECT POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU RE-OPTIMIZE AN ELISA METHOD WHEN A REAGENT LOT CHA OU IDENTIFY UNKNOWN METABOLITES? HOW DO YOU OPTIMIZE AN ANALYTICAL METHOD UNDER GMP? HOW DO YOU KNOW IF A BIOSIMILAR IS SIMILAR EN NOW RAW MATERIALS ARE PURE? HOW DO YOU EVALUATE PRODUCT PACKAGING? HOW DO YOU IDENTIFY THE SOURCE OF CONTAMINATION? HOW DO YOU AL TECHNIQUE TO USE? HOW DO YOU SIMULTANEOUSLY TEST FOR TWO BYPRODUCTS? HOW DO YOU CHARACTERIZE AN UNKNOWN? HOW DO YOU EVALUA, HUMID ENVIRONMENTS? HOW DO YOU KNOW RAW MATERIALS ARE PURE? HOW DO YOU KNOW IF A BIOSIMILAR IS SIMILAR ENOUGH? HOW DO YOU IDENTI LATIONS? HOW DO YOU PREDICT EFFECTS OF POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU EVALUATE CONTAINER/CLOSURE SYSTEMS? HOW DO G SAFER? HOW DO WE SPEED UP INNOVATION? HOW DO YOU GET A METHOD TO PERFORM AS EXPECTED? HOW DO YOU KNOW HOW DRUG IS DISTRIBUTED OW DO YOU MEASURE SURFACE ROUGHNESS? HOW DO YOU PREPARE A SCIENTIFICALLY SUPPORTED DEFENSE? HOW DO YOU TROUBLESHOOT A CHALLE HOW DO YOU PERFORM A STUDY THAT HAS NEVER BEEN DONE? HOW DO YOU ADJUST A FORMULATION FOR TIMED RELEASE? HOW DO YOU MAKE A DRUG ETERRENT? HOW DO YOU MAKE A METHOD MORE ROBUST? HOW DO YOU ENSURE A LINKER WON T BECOME TOXIC? HOW DO YOU GET A CLEARER SUPERN ONITOR ANALYTE CONCENTRATION OVER TIME? HOW DO YOU ADDRESS AN FDA RESPONSE LETTER ASAP? HOW DO YOU KEEP UP WITH CHANGING REGUL OU PREDICT EFFECTS OF POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU EVALUATE CONTAINER/CLOSURE SYSTEMS? HOW DO WE MAKE PACKAGIN E SPEED UP INNOVATION? HOW DO YOU GET A METHOD TO PERFORM AS EXPECTED? HOW DO YOU KNOW HOW DRUG IS DISTRIBUTED IN A PATCH? HOW D SURFACE ROUGHNESS? HOW DO YOU PREPARE A SCIENTIFICALLY SUPPORTED DEFENSE? HOW DO YOU TROUBLESHOOT A CHALLENGING METHOD? HOW A STUDY THAT HAS NEVER BEEN DONE? HOW DO YOU ADJUST A FORMULATION FOR TIMED RELEASE? HOW DO YOU MAKE A DRUG IS ABUSE-DETERRENT? A METHOD MORE ROBUST? HOW DO YOU ENSURE A LINKER How WON T do you BECOME reverse engineer TOXIC? HOW for Q1/Q2 DO YOU equivalency? GET A CLEARER How do SUPERNATANT? you determine the HOW grade DO YOU MONITOR RATION OVER TIME? HOW DO YOU ADDRESS AN FDA RESPONSE LETTER ASAP? HOW DO YOU KEEP UP WITH CHANGING REGULATIONS? HOW DO YOU PRED POST-TRANSLATIONAL MODIFICATIONS? HOW DO YOU EVALUATE of complex CONTAINER/CLOSURE excipients? How do you SYSTEMS? determine HOW the polymorph DO WE MAKE of an API PACKAGING in a semisolid SAFER? drug HOW DO WE SP product? Ask EAG. We Know How.

2 GENERIC PHARMACEUTICALS WE KNOW HOW How does EAG expedite the generic drug development process? EAG s Material Sciences division has been performing investigative analytical chemistry for the pharmaceutical industry for over 20 years, performing failure investigations, unknown particle identifications and material characterizations. However, with the development of the FDA s guidance for the generic industry, our role has evolved into full reverse engineering of Reference Listed Drugs (RLDs) and Reference Standards (RSs). Our primary focus is qualitative and quantitative analysis of excipients, the two critical factors that must be addressed when demonstrating Q1/Q2 equivalence to the RLD (Qualitative Equivalence and Quantitative Equivalence). Over the past four years, we have analyzed 140 different RLD systems ranging from topicals and transdermal patches to solid oral and ophthalmics. What is RLD Reverse Engineering? Reverse engineering is the process of completely understanding the RLD from excipient grade and quantity to API polymorphism and the exact location of each component. Although the API and excipients of a formulation are provided with a product insert, this information is rarely sufficient to develop a comparable formulation. At EAG Laboratories, we develop programs to answer our customers questions about RLD products, including: How much of each excipient is present? What grade of an excipient is present in the RLD? What is the polymorph of the API in a semi-solid? Is the API in our product equivalent to the RLD? Is it changing during formulation? How is the API distributed throughout the microbeads in an extended release capsule?

3 GENERIC PHARMACEUTICALS HOW WE OPERATE The EAG Difference As a premier scientific services provider, we recognize the importance of delivering results and answers to critical questions within a timeframe to make an impact. We foster a proper sense of urgency with our scientists and engineers, accomplished by: Capital resource management: In most cases within EAG, we have multiple pieces of instrumentation for our variety of techniques. This capacity allows back-up instrumentation in the event an instrument is out of service. Additionally, the multiple pieces of equipment increase our overall capacity for throughput, allowing delivery of results within a reasonable timeframe. Efficient scientific services process: We have developed a proprietary, in-house LIMS system, resulting in efficient sample management and throughput in the lab. Laboratory culture: Our scientists embrace an efficient laboratory culture and are passionate about delivering results to make a meaningful impact for our client s commercial success. We leverage our size and knowledge base to support generic pharmaceutical companies. We have been supporting generic companies for many years and understand the unique needs of this industry. When you work with EAG, you can expect: EAG LABORATORIES REVERSE ENGINEERING AT A GLANCE: EAG has over 20 years of experience in supporting the generic drug industry. 140 The number of independent drug products that we have performed reverse engineering studies on over the last four years. A dedicated team including a Ph.D. technical specialist, program director, and scientists A program kick-off discussion Weekly progress updates An easy to understand report with a chance to review prior to finalization. We want to make sure you are satisfied with the final product. 75 2,026 The number of topical formulations we have reverse engineered The total number of excipients that we have quantified in these studies. "Telling a customer that an RLD has 10% PVP in it is just not very helpful. They also need to know the exact grade/mw of PVP that was used." An EAG scientist The number of discreet excipients that we have encountered. The average number of days to completion of draft report for these studies.

4 GENERIC PHARMACEUTICALS TOPICALS AND OPTHALMICS Topical creams, lotions, ointments and gel analysis Roughly half of all the RLDs EAG has analyzed are topical creams, lotions, ointments and gels. With complex excipients, these systems require extensive analytical instrumentation and expertise. We are experienced in the separation and characterizations of RLD systems containing several excipients. A representative topical reverse engineering program will use a combination of techniques, including but not limited to: LC/MS, GC-MS, HPLC, GC, GPC, IC, ICP-MS, TGA, DSC, and Viscosity. Examples of complex excipients in topicals include: Hydrocarbons Mineral oils Waxes Polyols Modified celluloses Carbomers Siloxanes Mono-, Di-, and Triglycerides Surfactants EAG knows how to perform quantitation of excipients, from low-level single components to complex excipients experiencing major matrix effects or overlapping signals. After identifying the grade of material used as the excipient in the RLD, we then obtain reference standards of this material to use for quantitation. Whenever possible, we perform spiked additions to confirm the accuracy of our methodology. Some clients prefer to prepare their own formulations for our scientists to compare side-by-side with the RLD to further validate the data. Polymer analysis for transdermals Having been in the polymer analysis business for nearly 30 years, EAG Laboratories combines our knowledge and experience with pharma expectations to successfully reverse engineer many transdermal patches. We are well equipped with the polymer analysis techniques required for transdermals, such as MALS-GPC, DSC, TGA, DMA, TMA, Raman and FTIR. In addition to these, we also offer a wide range of cross-sectional analysis and mapping techniques (TOF-SIMs, Raman, FTIR, SEM-EDS, and X-Ray) to understand the 3D structure of the system, depth of layers, and the pinpoint location of each component in the product.

5 GENERIC PHARMACEUTICALS TRANSDERMALS & SOLID ORAL DOSAGES Solid oral dosage analysis From tablets to extended release capsules, we investigate many different dosage systems to see how they are put together. We perform excipient characterizations and quantitations using a simillar approach as other delivery systems. We also perform many cross-sectional studies to ascertain the location of the excipients within the capsule/tablet/bead to gain insight as to how the delivery system was constructed. We answer questions such as: Is there a sugar sphere core? Are there multiple applications of API or excipient form layers? Is there a disintegrant dispersed throughout the drug product with the API? Magnesium Lansoprazole TOF-SIMS cross-sectional images of an antacid drug product show the presence of Mg, both in the talc exterior and MgCO3 particles in the core; the API lansoprazole, and sucrose present with the lansoprazole. TOF-SIMS is extremely useful for APIs with an elemental makeup similar to the excipients present. While SEM-EDS data provides an elemental map, TOF- SIMS presents a molecular map from observing ions evolved from a surface. Sucrose Overlay

6 GENERIC PHARMACEUTICALS INVESTIGATIVE SUPPORT Particle Identification In addition to reverse engineering and characterization work, we also perform a wide variety of emergency contamination investigations and particle identifications. Particulate material commonly shows up in pharmaceutical raw materials, in-process samples and finished products. Understanding the identity of the species is required to determine root cause and evaluate potential corrective action plans. We have developed microanalytical methods using a combination of organic characterization and surface analysis techniques to provide insight into the chemistry of the unknown material. Whether the offending material is organic or inorganic based, EAG has the equipment needed for full characterization. Typically, we will use FTIR microscopy, Raman microscopy, XPS/ ESCA, and/or TOF-SIMS for organics and XPS/ESCA, Auger Electron Spectroscopy, SEM/ EDS or XRF to provide elemental information and additional speciation of inorganics. Contamination Identification In addition to particle identification work, we also analyze hazes, films, oils and residues appearing in final products as well as on equipment, containers or from any other point in the manufacturing process. EAG Laboratories is fully equipped with the necessary instrumentation, from FTIR, NMR, and Raman to GC-MS and LC/MS. By performing unknown characterizations for over 15 years, we have developed our own internal LC/MS library of mass spectral data of common contaminants. This information is extremely useful for quickly identifying impurities and helping our customers make informed decisions about their products. Impurity Identification During stability studies, new impurity peaks can arise that do not match those identified and profiled during forced degradation or extractable/leachable studies. Our team is experienced in performing rapid method transfers to replicate our client s chromatographic conditions. EAG can also convert HPLC methods to conditions compatible with LC/MS instrumentation. Once a suitable method is in place, we use LC with high resolution mass spectrometry (LC-HRMS) to identify the impurity and propose a structure. EAG can either acquire or synthesize a standard to confirm the incident peak. This material can then also serve as a reference standard for future stability tests.

7 GENERIC PHARMACEUTICALS CUSTOM SYNTHESIS & OTHER SERVICES CMC Analytical Support EAG Laboratories offers comprehensive CMC analytical support including multi-disciplinary, multi-technique analytical method development and validation, complete stability program management and in-depth extractables and leachables expertise. Our analytically focused CRO has deep experience in method development, program design and complex study execution. Custom Synthesis Our synthesis team brings unparalleled expertise to custom synthesis and small-scale manufacture of intermediates, impurities, analogs, metabolites, analytical standards, DEAcontrolled substances, and other chemical compounds. We have extensive experience with multi-step and other complex synthesis projects, and our full suite of analytical services ensures quick turnaround of purity and structural confirmation. We can generate material from mg to kg scale to meet your current and future needs. Our custom synthesis teams have expertise in: Small molecule synthesis Opioids Heterocycles chemistry Radiolabeled synthesis (14C, 3H) Steroids Impurity reference standards Other Services EAG Laboratories also performs API characterization ranging from XRD for polymorph characterization to DSC, TGA, Raman and other techniques. We also perform particle size investigations of APIs or excipient particles in semi-solid matrixes using microscope Raman with mapping. Additional services our generic pharmaceutical clients have found helpful include: Glass delamination investigations using SIMS Physical characterizations Polymer analysis Elemental analysis We understand urgency We recognize the importance of urgency in product investigations, with a highly efficient and cost-effective approach to contaminant and particle identification. EAG s dedicated team guarantees same-day response from a technical specialist.

8 GENERIC PHARMACEUTICALS PHARMACEUTICAL CHARACTERIZATION GUIDE Organic Techniques Elemental Thermal Imaging XRD Surface Physical LCMS HPLC GCMS GC Pyro-GCMS FTIR NMR Raman GPC Ion Chromatography ICP-OES ICP-MS GDMS IGA XRF TGA DSC Optical Microscopy Optical Profilometry SEM-EDS TEM/STEM Raman Microscopy AFM TOF-SIMS XRD SIMS XPS/ESCA Tensiometry Viscometry Grade Determination Excipient Quantitation RLD Construction Microstructure API Polymorph and Characterization Unknown Compound Investigation Particle/Contaminant Investigation Glass Delamination Elemental Physical Characterization Polymer Metallurgical EAG Laboratories is a global scientific services company serving clients across a vast array of technology-related industries. Through multi-disciplinary expertise in the materials, engineering and life sciences, EAG helps companies innovate and improve products, EAG.COM ensure quality and safety, strengthen supply chains, protect intellectual property and comply with evolving global regulations.