Analytical Testing Services

With expert chromatography laboratory analysis, we’ll reduce your time-to-market, optimize the purity of your APIs and intermediates and get you to your target molecule with a better understanding of the process.

You can rely on our team to quantify and identify your substances and compounds from our state-of-the-art facilities where we deliver routine and advanced analytical testing, with detection levels down to ultra trace-levels.

Our skilled scientists offer a variety of chromatographic expertise and techniques to analyze your compounds:

• HPLC and UPLC/UHPLC instrumentation with a wide variety of detection capabilities (UV, DAD, RI, MS, MALS) to determine sample assay and purity of samples, along with quantitation for solubility, dissolution, diffusion and other techniques requiring quantitation
• Use of your methods, qualification of compendial methods and full method development, including forced degradation and identification of impurities
• Preparative chromatography services
• Ion chromatography for use in a wide variety of applications, including quantitation of API salts

We deliver a comprehensive end- to- end service including a combination of analytical techniques to determine or confirm the solid state molecular structure for your chemical entity.

We combine innovative techniques and approaches to address your complex structural problems to get your compound where it needs to go:

• Mass spectrometry
• NMR spectroscopy
• Infrared spectroscopy
• Elemental analysis
• Single crystal X-ray diffraction

Our committed biochemistry team offers unmatched data and scientific interpretation, providing cGMP support for all stages of your biopharmaceutical development through to manufacturing.

We pair ultra-high resolution mass spectrometry with our industry-leading expertise to achieve data and scientific interpretation that is unmatched in the contract preclinical research industry.

We specialize in:

• Method development, validation and transfer
• cGMP batch release testing
• Impurity characterization and identification
• Drug substance, product stability and comparability studies
• Protein/peptide crystallization
• Solid state characterization (critical for lyophilized drug products)

Ultra-high resolution Q-TOF mass spectrometry

We provide ultra-high resolution Q-TOF mass spectrometry services for large and small molecule analyses. The Bruker maXis-Plus Q-TOF mass spectrometer is a state-of-the-art instrument that offers significantly enhanced capabilities in analysis and data interpretation for small and large molecules, including biologic drugs, metabolites and polymers to meet the expectations outlined in the ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products.

Our advanced spectrometry technique delivers numerous benefits in terms of speed, sensitivity and accuracy:

• Unambiguous assignment of molecular formulae for small molecules to larger molecules, including biologic drugs, metabolites and polymers: This mass resolving power enables analyses in the presence of complex matrices (such as biological and petrochemical).
• Identification of active and/or high-percentage metabolites in drugs to meet the requirements of the FDA Metabolites in Safety Testing (MIST) guidance: Q-TOF mass spectrometry is a fast and accurate analytical method for characterizing low levels of analytes. High-resolution mass spectrometry can provide MIST information early in the development path.
• Enhanced sensitivity: This is particularly important for impurity assays of drug substances and drug products. The limit of detection is in the pg/mL to fg/mL range.
• Extreme mass range: The Q-TOF MS has a range from 20 Da to 40,000 Da (assuming a singly charged species; far larger masses can be analyzed if multiple charges are present). This enables analyses of small molecules, polymers, carbohydrates, oligonucleotides and proteins such as antibodies.
• UPLC compatibility for LC-MS: UPLC chromatography is typically five to 10 times faster than HPLC with up to two to three times the chromatographic resolution. This means much faster sample analyses and generally easier method development. Higher throughput enables more rapid turnaround for large numbers of samples.
• CAD detection for UPLC: In addition to standard UV detection, state-of-the-art charged aerosol detection is available to enable analyses of materials without UV chromophores.
• MS and MS/MS capability for a wide range of molecules combined with detailed interpretation of the results: This allows us to obtain the most information from a limited amount of sample.
• MS of biologic drugs such as proteins, oligonucleotides, carbohydrates and other polymers both biological and nonbiological: Sequencing of proteins from the N-terminus or C-terminus is also possible.

In addition to state-of-the-art mass spectrometry capabilities, we offer a wide range of analytical technologies to characterize biologics and biosimilars, such as:

• HPLC (RP, IEX, SEC, IC), gel electrophoresis (SDS-PAGE/Native PAGE; IEF) for separation and purity evaluation
• N-terminal Edman sequencing and amino acid analysis for protein identification
• MALDI-TOF MS for molecular weight determination
• Dynamic light scattering, SEC MALS and SEM for aggregation state evaluation
• Numerous spectroscopic techniques (NMR, UV/VIS, IR and Raman) for fingerprinting of macromolecules
• Ligand binding and activity assays with LAL endotoxin testing to support batch release of biologicals and biosimilars

Partner with us and you’ll leverage our expertise and the most powerful methods for the study of crystalline and partially crystalline solid state materials.

We’ll meet your most complex physical characterization requirements.

X-Ray Powder Diffraction

We have extensive experience in the interpretation of powder diffraction patterns and have developed unique methodologies for fully automated recognition of crystalline forms.

X-ray powder diffraction (XRPD) is one of the most powerful methods for the study of crystalline and partially crystalline solid-state materials.

We have a range of controlled humidity and temperature chambers where the thermodynamics of these various crystallines and disordered forms can be studied in situ and in real-time.

We offer various sample presentation methods allowing samples to be studied in solid, powder, suspension, cream or melt form to suit your specific requirements. Our expert scientists have developed approaches to overcome common sample limitations such as inhomogeneity, preferred orientation and particle statistics. Extremely small amounts of material can be analyzed using these techniques.

Indexing

Our patented TRIADS™ algorithm is an essential tool in the determination and confirmation of crystalline phase purity.

X-ray powder diffraction pattern indexing is the first step in the solution of a crystal structure from powder data but can also be used to determine if a given pattern represents a pure solid phase. The latter information is often sufficient to ensure product homogeneity if a crystal structure is unavailable.

Single Crystal X-Ray

An unequivocal method of solid form identification, and one preferred by the FDA when possible, is single crystal X-ray structure determination.

Our expert scientists employ the most modern methods, including a state-of-the-art Rigaku SuperNova diffractometer equipped with a micro-focus X-ray source and HPAD detector. This allows the determination of structures using smaller crystals than are required for conventional equipment.

Calculation of Powder Patterns

Our experts use multiple software methods to calculate powder patterns from crystal coordinate files.

Once the crystal structure of a material has been determined, we can calculate an XRPD pattern. The calculated powder pattern provides information about homogeneity of the crystalline phase and serves as an unequivocal pattern for use as a standard for polymorph screening or quantitative analysis of multiphase samples. We can build parameters such as crystallite size, morphology and preferred orientation into the pattern calculation, providing insight into the microstructure of single-phase samples. Microstructural parameters often play a significant role in the physical and chemical properties of a sample.

We can study disordering processes to identify relationships between crystalline phases and microcrystalline/amorphous phases. The subsequent calculated amorphous patterns can be used for precise crystallinity analysis if pure amorphous forms of the material are not available for measurement. We offer a wide range of tools for the calculation of powder patterns starting from crystal coordinate files, D and I files or reference patterns.

Rietveld Analysis

Our experts use the Rietveld method to separate overlapping data from a typical XRPD pattern and allow accurate determination of the structure of a compound. We use this method to address various problems including quantitation using XRPD patterns with high degrees of overlap.

Crystal Structure Determination From X-Ray Powder Diffraction

We perform structure solution using simulated annealing and have a long track record of solving structures from powder data. Although we have experience with synchrotron data, in most cases good results can be obtained using our in-house, high-resolution XRPD data.

Leverage our expertise in particle characterization and we’ll help you understand the manufacturability of your compound. We deliver characterization of powder properties for APIs in development and for commercial batch release testing.

Particle size distribution, particle shape (morphology), surface area, as well as bulk and tapped density can all impact the performance and quality of your final drug product.

Particle size and surface area are directly correlated to the dissolution rate of an API which may impact bioavailability for poorly soluble drugs. How easily a powder can be handled, flow or be blended with other powders, such as excipients, may also be a determining factor for the quality and performance of a drug product, e.g. to ensure good content uniformity.

Our skilled scientists offer cGMP testing of particle properties using the following techniques:

• Particle size analysis by laser light scattering, for the characterization of particles in the approximate size range ~0.01-3500 µm (dependent on dispersion unit and material evaluated). Development, transfer and/or validation of analytical methods are performed by experienced scientists following ICH and USP guidelines. Available instrumentation include: 
  • Malvern Mastersizer 2000 with the following dispersion units for wet and dry methods: 
    • Hydro 2000µP (wet)
    • Hydro 2000S (wet)
    • Hydro 2000SM (wet)
    • Scirocco (dry)
  • Malvern Mastersizer 3000 with the following dispersion units for wet and dry methods: 
    • Hydro MV (wet)
    • Hydro SV (wet)
    • Aero S (dry)
• Sonic sieving
• Particle counter by light obscuration (AccuSizer particle counter and sizer)
• Microscopy
• Particle morphology and size range by image analysis
• Scanning Electron Microscopy (SEM)
• Surface Area and porosity analysis by BET technique 
  • Micromeritics Gemini V and VII models
  • Micromeritics TriStar (N2 and Kr)
• Bulk and Tapped Density

We’ll solve your solid state characterization challenges with integrated capabilities, including light microscopy, fluorescence, infrared, Raman and scanning electron microscopy

Our experts routinely use results from microscopy studies to complement analytical data from other techniques to meet your solid state characterization needs.

Microscopy with appropriate sample handling is also a powerful tool for trace analysis.

Access our complete microscopy capabilities:

• Light microscopy including polarizing, bright field and dark field
• Fluorescence
• Infrared (IR)
• Raman
• Scanning electron microscopy (SEM) 
  • High vacuum
  • Low vacuum
  • Energy dispersive X-ray analysis (EDX)
• Hot stage (light microscopy, IR, Raman)
• Cold stage (light microscopy, IR, Raman)
• Stereomicroscopy

With proven expertise in molecular spectroscopy we offer a broad range of techniques to help you get your compound where it needs to go.

Molecular spectroscopy offers numerous benefits for the characterization of solid state materials:

• Qualitative and quantitative analysis
• Real-time monitoring of transient species
• The ability to study API or drug product
• Process analytical technology (PAT) application

We actively apply molecular spectroscopy for both standard compendial methodology and high-end research applications. With our wide range of spectroscopic instrumentation you can be confident we will apply the appropriate technology to your needs.

Infrared and Raman Spectroscopy

Our skilled scientists perform solid state analyses with state-of-the-art infrared (IR), near IR (NIR) and Raman spectrometers.

These techniques provide both qualitative characterization of different solid forms and a means to quantitate the solid form composition within the drug substance or product.

• Infrared spectroscopy 
  • Diffuse reflectance
  • Alkyl halide pellet
  • Mineral oil mull
  • TG/IR
  • Microspectroscopy
  • Variable temperature diffuse reflectance
  • Variable humidity diffuse reflectance
  • Attenuated total reflectance
  • Grazing angle
  • Chemical mapping
• NIR spectroscopy imaging
• Raman spectroscopy 
  • Dispersive and FT-Raman spectrometers
  • Microspectroscopy
  • Chemical mapping
  • Variable temperature

UV/Visible Spectroscopy

We apply ultraviolet/visible absorption spectroscopy in support of dissolution, stability and solubility studies.

NMR Spectroscopy

Our scientific experts provide customized data interpretation, delivering maximum value. We conduct our studies in full cGMP compliance with U.S. and European regulations to ensure the highest quality data, interpretation and experimental consistency.

Our highly skilled team performs both solid state and liquid state cGMP nuclear magnetic resonance (NMR) spectroscopy to characterize a wide variety of materials from small inorganic and organic compounds. We have the capabilities to analyze specific nuclei such as 19F in both solids and liquids because they are present in about 20 percent of pharmaceutical drugs.

We have NMR capabilities for analyzing large biologics (e.g. biopolymers, unmodified and modified peptides, proteins, DNA, RNA), which are the fastest growing type of molecules currently being developed as drugs. NMR spectroscopy delivers higher resolution and sensitivity with modern spectrometers.

Curia provides a complete suite of capabilities with small molecule, synthetic polymer and biologics NMR spectroscopy:

• 1D 1H and 13C NMR spectroscopy with 19F, 31P, 29Si available as routine analyses.
• 2D NMR analyses such as COSY, NOESY, TOCSY, HMQC, HSQC and HMBC with specific resonance assignments to provide detailed information on chemical structure and conformation in solution
• Compendial NMR methods in accordance with EP or USP/NF specifications
• Qualitative and quantitative NMR (qNMR) including method development and validation for all available liquids and solids NMR techniques; most of our validated methods are used for clinical or commercial lot release or stability studies
• Comparability and sameness studies of biologics due to the sensitive and accurate fingerprint of the molecular conformation extracted from the NMR data
• Identification and quantitation of known and unknown impurities
• Characterization of polymorphs, solvates, salts, cocrystals and amorphous solids
• Chemical structure identification
• Analysis of formulations
• Analysis of stereoisomers
• Determination of the number of molecules in an asymmetric unit
• Chemical exchange analysis
• Molecular motion analysis
• Conformational/structural analysis; 3D chemical structure determination of small molecules and biologics using NMR restrained molecular dynamics (MD) simulations
• 300−600 MHz NMR spectrometers, some of which can analyze both solids and liquids

Liquid State NMR

Our expansive spectroscopy portfolio also includes liquid state NMR spectroscopy. We can quickly determine molecular structure, dynamics and conformation as well as analyze specific components in a mixture either qualitatively or quantitatively.

Solution NMR spectroscopy provides a sensitive method to quantify impurities, reaction products or residual solvents including water. A large variety of methods for NMR spectroscopy of liquid solutions is available at 300 ‒ 600 MHz (1H). Variable temperature experiments are also available. Some of the most common analyses include 1D NMR of 1H, 13C, 19F, 15N and 31P NMR. We also perform more advanced 2D NMR analyses. We apply these techniques to determine the assignments of specific resonances for a molecule, which can provide the necessary information to obtain a molecular conformation in solution.

• 5 mm double resonance pulsed field gradient (PFG) cryo-, and room temperature probes for high sensitivity on the X and Y channels (useful for typical small organic molecules and biologics)
• 5 mm inverse detection PFG probes (useful for biologics and typical small organic samples)
• 5 mm dual broadband PFG probes (ideal for organic and inorganic materials to observe 13C, 15N, and other lower frequency nuclei or those nuclei with low natural abundance)
• Z-axis gradient capabilities for performing many of the newest pulsed field gradient experiments
• Wide range of 2D NMR spectroscopic techniques available for structural elucidation
• Variable temperature capabilities from −150 °C to 150 °C
• Sample quantities in ~0.5 mL solvent
• 1H or 19F – 0.01-5 mg, 31P – 1-20 mg, 13C – 1-50 mg

Solid State NMR

Optimize the analysis of polymorphs, solvates, salts, cocrystals, amorphous solids and formulations with magic angle spinning (MAS) Solid state (SS) NMR spectroscopy.

We perform MAS SSNMR spectroscopy at 400 MHz (1H) for most of the NMR active nuclei on the periodic table. Variable temperature experiments can be performed from −75°C to 100°C.

We conduct standard direct excitation or enhancement via ramped amplitude cross-polarization, modulated high-power proton decoupling, very high-speed spinning (up to 18 kHz), spectral editing and spinning sideband suppression. Our capabilities and technologies include:

• Agilent T3 narrow-bore double and triple resonance 4 mm SSNMR probes
• Doty Scientific 4 mm HF SSNMR probe specifically designed for simultaneous 1H decoupling while detecting 19F or the reverse
• Doty Scientific 4 mm HFX SSNMR probe specifically designed for simultaneous 1H decoupling while detecting 19F or X nuclei or 19F decoupling while observing X
• Low frequency: Observe any NMR active nucleus with a resonance frequency between 15N (~40 MHz) and 31P (~162 MHz)
• High frequency: Observe or decouple 1H (~400 MHz) and 19F (~376 MHz) nuclei
• MAS and CP/MAS available up to 18 kHz spinning speed (with modern phase modulated decoupling and/or TOSS spinning sideband suppression) to offer the highest data quality
• Simultaneous 1H and 19F decoupling while observing on the X-channel or 1H decoupling while observing 19F
• 2D correlation spectroscopy of common nuclei (1H, 13C, 15N, 19F, 29Si, 31P)
• 2D MQMAS or STMAS of quadrupolar nuclei
• Variable temperature capabilities from −75 °C to 100 °C
• Sample quantities: 40−50 mg (optimal), 5−10 mg (possible)

Our expert scientists are on hand to quickly quantify any trace or heavy metals in your pharmaceutical product.

We leverage our robust capabilities in inductively coupled plasma mass spectrometry (ICP-MS) to streamline the detection of trace metals at levels as low as parts per trillion.

We have the knowledge to perform USP <232> and USP <233> testing, including heavy metals and other products:

• Drug substances
• Excipients
• Drug products
• Dietary supplements

For improved sample preparation, our highly skilled team uses the UltraWAVE microwave digestion apparatus for hard-to-solubilize samples, as well as reliable techniques such as aqua regia and hydrofluoric acid.

Our ICP-MS can detect and measure the following metals:

• Aluminum, arsenic, antimony
• Barium, bismuth
• Cadmium, cobalt, calcium, copper
• Germanium, gold
• Indium
• Iron
• Lead, lithium
• Magnesium, manganese, mercury, molybdenum
• Nickel
• Palladium, platinum
• Potassium
• Selenium
• Silver, sodium
• Tin, titanium, thallium
• Yttrium
• Zinc, zirconium

Partner with us for analytical testing to mitigate the risks associated with glass delamination, including safety issues and costly market recalls.

Our skilled scientists apply a proactive approach to ensure compliance with cGMP practices including stability studies and glass delamination testing. 

We offer a range of comprehensive glass delamination studies for pharmaceutical glass containers, helping you to mitigate risks associated with the generation of lamellae from the inner surface of a glass pharmaceutical container.

Our experts deliver critical testing of your drug product for the presence of lamellae and test the interior surface of the glass container for evidence of glass delamination or pitting.

Glass Delamination Studies According to USP 1660

The recommended approach is to evaluate the potential of a drug product to cause formation of glass particles (precipitated glass which was dissolved via etching of glass from the inner surface of the glass container) and delamination of the inner surface of the container.

Our screening studies can comprise a number of analytical techniques to examine three key parameters:

• Visual examination and chemical profiles of the inner surface layer
• Amount and identity of extracted elements in the drug product solution
• Number of visible and sub-visible particles in solution

The evaluation of the inner surface of glass containers begins with the Surface Glass Test under guidance of USP or EP, in which water is used as the extracting medium, followed by a series of analytical techniques to screen for the inner surface of the container for evidence of glass delamination, pitting, and glass precipitation or glass particulates.

Our scientific expertise is combined with unique thermal analysis equipment to help characterize your materials and guide your compound through development.

We monitor thermochemical events and weight loss as a function of temperature to achieve insight into solid form characteristics, mechanisms of polymorphic transformations and solid state degradation pathways.

To analyze these properties of bulk and formulated solid products, we simultaneously collect thermal gravimetric analytical (TGA) and differential scanning calorimetry (DSC) data.

DSC, Modulated DSC

Differential scanning calorimetry is one of the most widely used thermal analysis techniques for the characterization of pharmaceutical solids. Our expert scientists measure thermal events such as melting, recrystallization, decomposition and glass transitions. We are skilled in performing quantitative mixture analysis (i.e., determination of polymorph mixtures). Modulated DSC offers expanded capabilities by allowing for the measurement of heat capacities and the characterization of reversible and non-reversible thermal transitions.

Melting Point

Melting point determination is an important aspect of polymorph analysis in terms of stability. We provide melting point determination per the various methods outlined in the USP.

Thermogravimetric Analysis and Thermogravimetric/Infrared Analysis

Benefit from our thermogravimetric analysis to measure the thermally induced weight loss of a sample as a function of temperature. In conjunction with DSC and hot-stage optical microscopy, TGA provides an excellent approach to the determination of thermal properties of the pharmaceutical material.

Extending the TGA technique to thermogravimetric/infrared analysis (TG/IR) provides the ability to not only measure thermally induced weight loss, but also to chemically identify the volatile component during each weight loss step. As a volatile component evolves from the sample in the TG furnace, it is swept into a gas-phase IR cell for spectroscopic analysis and potential chemical identification. TG/IR is an ideal technique for solvate and hydrate analysis.

Hot-Stage Optical Microscopy

Our technical expertise allows us to incorporate hot-stage optical microscopy in conjunction with differential scanning microscopy, thermal gravimetric or thermal gravimetric/infrared, to characterize the thermal properties of your pharmaceutical solid.

We provide analysis with two different hot-stages that allow for controlled temperature experiments from -196 to 600 °C. We can also capture video or digital images of visual thermal events such as melting, recrystallization or volatilization.

Isothermal Microcalorimetry

We are able to study a wide variety of physical and chemical processes via isothermal microcalorimetry:

• excipient compatibility
• amorphous content
• degradation rate
• relative stability of polymorphs
• process associated with a change in enthalpy

Our best-in-class instrumentation includes specialized accessories that allow control of the relative humidity and oxygen content of the sample environment.

Solution Calorimetry

To measure the heat of a solution of a solute as it dissolves in a solvent we use solution calorimetry. This measurement can be used for:

• detection and quantification of polymorphs and amorphous material
• determination of the relative stability of polymorphs
• monitoring dissolution processes

Our comprehensive instrumentation includes both semi-adiabatic and isothermal solution calorimeters.

Our leading experts are on hand to identify and mitigate contamination in your products or processes, helping you to avoid manufacturing inefficiencies, compromised product quality and delays in getting your product where it needs to go.

With access to innovative analytical techniques, we are ready to respond precisely to your needs, giving you the tools necessary to accelerate the decision making process.

Gaining an understanding of where the particulates first appear and the extent to which they appear can help to determine which analytical techniques are most appropriate.

Our expert scientists use microscopy and spectroscopy techniques to rapidly characterize contaminants, providing you with important information to help investigate and resolve any issues.

Contaminants may be identified by microscopical examination of their morphological characteristics; their shapes and forms are extremely important features in their analysis and tracing of their origins.

Particles can be visually distinguished from the raw materials, materials in intermediate process steps or the final product. In our experience, particulate matter can appear from four major sources of contamination:

• Raw materials such as packaging
• Working environment
• Processing steps
• Instability of the container or product.

Unknown Particulate Testing Services

Our technical team offers the following microscopy and microanalytical techniques relevant to the characterization of unknown particulates:

• FEI Quanta 200 ESEM
• Energy Dispersive X-ray (EDX)
• Leica DMLP Compound Polarized Light Microscope
• Leica Stereomicroscope, MZ6, MZ12.5 and M80
• Leica Polarized Light Stereomicroscope, DMLP
• Linkam Hot/Cold Stage (–196 to +350 °C)
• Linkam Lyophilization Stage (freeze drying, –196 to +100 °C)
• Nikon Optiphot-pol Compound Polarized Light Microscope
• Wagner & Munz Kofler Hot Stage and Hot Bar
• Continuµm Fourier Transform Infrared (FT-IR) Microscope with Fluorescence illumination capabilities
• Raman Microspectrometer

Contaminant Analysis Services, USP <788> and <789>

As a cornerstone to the support services required for characterization of unknown particulates, we are committed to providing expert services to support contaminant analysis, specifically for injectable products.

Our suite of best-in-class analytical technology includes a Particle Sizing Systems AccuSizer 780 SIS. This Single Particle Optical Sensing (SPOS) system, also known as light obscuration, is used to count and size particles between 0.5 to 400 micrometers. The system is operated in a HEPA-filtered laminar flow hood designed to create a Class 100/ISO 5 work environment and uses a syringe pump to pull accurate and precise aliquots of liquid samples through a light obscuration sensor.

This technique allows our skilled microscopists to conduct USP <788> (Particulate Matter in Injections) and USP <789> (Particulate Matter in Ophthalmic Solutions) to characterize extraneous, undissolved sub-visible particles unintentionally present in the solutions using light obscuration and microscopic particle counting (Methods 1 and 2). For both USP <788> and <789>, Method 2 is also available for microscopic counting of particles collected on a membrane filter or for liquid samples that exceed the particle count parameters as stated in Method 1 for either General Chapter.

Whether you need a two-week service or an accelerated turnaround, we can meet your most demanding timelines. We have the expertise, size and capacity to easily match your material testing needs.

We offer comprehensive USP-NF, EP, FCC and JP monograph testing for many raw materials used in pharmaceutical products.

Our unique FDA-regulated, GMP laboratory provides complete gas testing services following USP test procedures and a dedicated quality assurance group routinely audits each area for strict compliance with cGMP requirements.

You can rapidly access a complete suite of chemistry-based testing of raw materials, including excipients and active APIs. 

USP/NF compendial analytical testing capabilities

• <181> Identification – Organic Nitrogenous Bases
• <191> Identification Tests – General
• <197> Spectrophotometric Identification Tests
• <201> TLC Identification Test
• <206> Aluminum
• <211> Arsenic
• <216> Calcium, Potassium, and Sodium
• <223> Limit of Dimethylaniline
• <221> Chloride and Sulfate
• <228> Ethylene Oxide and Dioxane
• <231> Heavy Metals
• <232> Elemental Impurities – Limits
• <233> Elemental impurities – Procedures
• <241> Iron
• <251> Lead
• <261> Mercury
• <271> Readily Carbonizable Substances
• <281> Residue on Ignition
• <291> Selenium
• <311> Alginates Assay
• <341> Antimicrobial Agents Content
• <661> Containers
• Benzyl Alcohol
• Chlorobutanol
• Phenol
• Methylparaben and Propylparaben
• <401> Fats and Fixed Oils
• Specific Gravity
• Melting Temperature
• Acid Value
• Ester Value
• Hydroxyl Value
• Iodine Value
• Peroxide Value
• Saponification Value
• Fatty Acid Composition
• <415> Medical Gases Assay
• <431> Methoxy Determination
• <461> Nitrogen Determination
• <466> Ordinary Impurities

USP/NF analytical testing capabilities

• <469> Ethylene Glycol, Diethylene Glycol and Triethylene Glycol in Ethoxylated Substances
• <467> Residual Solvents
• <471> Oxygen Flask Assay
• <525> Sulfur Dioxide
• <591> Zinc
• <611> Alcohol Determination
• <616> Bulk Density and Tapped Density of Powders
• <621> Chromatography
• <631> Color and Achromity
• <641> Completeness of Solution
• <643> Total Organic Carbon
• <645> Water Conductivity
• <651> Congealing Temperature
• <691> Cotton
• <695> Crystallinity
• <698> Deliverable Volume
• <701> Disintegration
• <711> Dissolution
• <721> Distilling Range
• <731> Loss on Drying
• <733> Loss on Ignition
• <741> Melting Range or Temperature
• <781> Optical Rotation
• <785> Osmolarity
• <786> Particle Size Distribution
• <788> Particulate Matter in Injections
• <791> pH
• <831> Refractive Index
• <841> Specific Gravity
• <851> Spectrophotometry and Light Scattering
• <891> Thermal Analysis
• <905> Uniformity of Dosage Units
• <911> Viscosity
• <912> Rotational Rheometer Methods
• <921> Water Determination

Other tests

• Monograph-specific chemical, microbiological and physical tests
• FCC monograph-specific chemical and physical tests
• European Pharmacopoeia (EP) testing
• Japanese Pharmacopoeia (JP) testing
• Physical and physiochemical methods, identification, limit tests, assays and biological tests
• General tests and monographs
• Testing per client/vendor methods
• Validation of compendial methods
• Verification of compendial methods

The particle properties of a powder — such as particle size, shape, surface area and porosity — can affect both the performance and process ability of a drug due to their effect on dissolution, stability, handleability and flow properties, impacting critical attributes such as tablet uniformity or suspension stability. Micromeritics is the study of particles and their properties, and pertains to powders, suspensions and emulsions.

We offer micromeritics capabilities, including fit-for-purpose method development and routine analytical services for:

• Particle size analysis
  • Laser light scattering (Malvern Mastersizer 2000 and 3000 instruments, equipped for dry and wet analysis)
  • Sonic sieving
  • Dynamic light scattering
  • Light obscuration (AccuSizer particle counter and sizer)
  • Microscopy and image analysis
  • Particle morphology and size range
  • Scanning electron microscopy (SEM)
• Surface area analysis by BET technique
  • Micromeritics Gemini V and VII models
  • Micromeritics TriStar (N2 and Kr)
• Bulk and tapped density
• Density

We go above and beyond to help you identify any obstacles to the development of your compound.

Our experts will collect, analyze and summarize all data necessary for your regulatory documentation needs and help ensure that your compounds comply with industry regulations. 

We can help compile your initial drug substance characterization (IDSC) report containing physical characterization and preformulation data for your IND filing. 

Physical characterization data includes:

• Form identification
• Solvent identification
• Hygroscopicity
• Micromeritics
• Structure elucidation.

We can also perform polymorph screening and form identification. Preformulation data includes equilibrium solubility, pH solubility, partition coefficient, pKa determination and accelerated physical and chemical stability.

For your regulatory submission, we can easily collect all or part of the IDSC package and summarize the information in a scientifically and QA-reviewed report that provides all the necessary data.

Our capabilities include:

Structure Elucidation

• Nuclear magnetic resonance (NMR)
• Solution NMR spectroscopy
• IR spectroscopy
• Single crystal structure determination
• Mass spectrometry

Physical Characterization

• X-ray powder diffraction
• Optical microscopy
• Differential scanning calorimetry
• Thermogravimetry
• Melting point determination
• Moisture sorption/desorption isotherms
• Infrared spectroscopy
• Raman spectroscopy
• Solid state NMR spectroscopy
• Ultraviolet spectrum
• Particle size distribution
• Surface area
• Scanning electron microscopy

Preformulation Data

• Equilibrium solubility
• pH solubility
• pKa determination
• Log P
• Log D
• Accelerated physical and chemical solid and solution stability

We offer state-of-the-art cGMP techniques and analytical method development for the isolation, identification and in vitro and in vivo characterization of proteins and other large molecules.

Our team provide you with knowledge on how to utilize the crystalline state of your molecule to stabilize proteins in formulations leading to faster development and improved products as well as greater control and reproducibility.

We have the ability to do detailed characterization of biologics in solid state, satisfying all regulatory requirements and supporting your IND filing. 

Capabilities

• Mass spectrometry
• Capillary electrophoresis
• Chromatography – HPLC, UPLC
• NMR 

We deliver comprehensive analytical services for the testing of materials, finished products, container and package systems.

Partner with us and we’ll help you meet the required quality standards established by key regulatory agencies while concentrating your resources on development.

With years of experience in the pharmaceutical, cosmetic and consumer industries our experts have handled a diverse list of products and specifications. We are skilled in providing guidance to ensure your product receives the appropriate testing.

As an FDA-regulated, DEA-licensed, ISO 17025 and ISTA-certified contract service provider we are ideally placed to support many clients, including those in the pharmaceutical, medical device, personal and consumer product industries.

Our renowned, stand-alone facility is dedicated to USP <51>, USP <61> and USP <62> testing, covering raw materials through finished products. Innovative equipment includes world-class incubators, ovens and fume hoods.

Our client-focused experts conduct tests that include:

• USP <51> Antimicrobial Effectiveness Testing required for developmental formulations through finished products stability
• USP <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests required to ensure that a product’s preparation complies with a preset specification for microbiological quality
• USP <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms including S. aureus, P. aeruginosa, E. coli, Salmonella species, Clostridium species, fungal organisms and a qualitative MPN for bile-tolerant gram negative bacteria
• USP <87> Biological Reactivity Tests, In Vitro
• USP <1231> Water for Pharmaceutical Purposes
• Standard Methods – For the Examination of Water and Wastewater

Our skilled quality assurance team works with you to develop gas testing protocols and validation reports to ensure your company meets FDA requirements for medical/process gas usage.

We offer comprehensive gas testing services, applying specialized expertise and technology to deliver the following gas testing capabilities:

• USP/EP Nitrogen
• USP/EP Oxygen
• USP/EP Carbon Dioxide
• USP/EP Helium
• USP/EP Medical Air

To reduce the likelihood of sampling errors and test failures, we offer comprehensive on-site sampling.

We also offer sample cylinder rental and shipping, providing complete instructions for sample processing. Our extensive inventory of stainless steel sample cylinders undergo a routine, extensive cleaning process to support your needs.

Streamline your solvent testing with our comprehensive testing capabilities.

Our skilled analysts have three decades of experience analyzing pharmaceutical products for residual solvents and can test your raw materials, intermediate and final products at any stage of development.

Residual solvents in pharmaceutical products are organic volatile compounds used or produced in the manufacturing of drug substances or excipients, in the preparation of drug products or from packaging and storage.

The USP <467> classifies solvents by their toxicity levels and potential adverse effects. We deliver robust testing for various classes of solvents to help you quickly ensure the safety and quality of your pharmaceutical product.

Our experts screen, confirm, identify and quantify multiple classes of solvents:

• Class 1 solvents (known to cause unacceptable toxicities or to have environmental effects) must be avoided in the manufacturing process of drug substances, excipients or pharmaceutical products unless their use can be justified in a risk-benefit assessment.
• Class 2 solvents (associated with less severe toxicity) must be limited in order to protect patients from potential adverse effects.
• Class 3 solvents (less toxic), which pose a lower risk to human health, are allowed where practical. Residual solvents concentration of 50 mg per day or less, corresponding to 5000 ppm, are acceptable without justification.

Rely on us for complete solid state biopharmaceutical capabilities. We offer state-of-the-art cGMP techniques and analytical method development for the isolation, identification and characterization of proteins and other large molecules. We aim to provide you with knowledge of how to utilize the crystalline state to stabilize proteins in formulations. Exploration of the solid state properties of biomolecules can not only lead to faster development and improved products but also greater control and reproducibility.

We have the expertise to solve your sorption and desorption testing challenges.

Our technical experts investigate the moisture uptake of samples at various relative humidities and temperatures using moisture sorption balances and/or gravimetric methods. We can fully characterize any new forms observed.

The water sorption/desorption profile of a solid provides key information about the physical stability of solid forms, especially hydrates. Our innovative techniques may also be used to quantitate amorphous material in your drug substance.

Organic vapor sorption and desorption

Our expertise extends to organic vapor sorption which can provide information on solvated forms and quantitation when water sorption may not be appropriate. Our scientists can also assess the physical stability of amorphous materials using various organic vapors.

We offer a complete suite of water analysis testing services to help guide the development of your drug product.

Water plays an important role in solid state pharmaceutical systems due to its impact on the chemical and physical stability of a drug substance and drug product. It also affects key physical properties that influence storage conditions.

Our team of experienced technical staff works with you to develop and deliver water testing and analytical solutions that add value to your project.

We use various innovative techniques to provide information on water content, hygroscopicity and hydrate formation, including:

• Karl Fischer (volumetric or coulometric)
• Loss on drying (LOD)
• Thermal gravimetric analysis (TGA)
• Dynamic vapor sorption (DVS)
• Controlled relative humidity (RH)-XRPD
• Relative humidity chambers

We can help you check the safety, quality and performance of your personal care products and systems to keep your brand protected.

Partner with us and for access to superior chemistry testing of personal care raw materials and products, in accordance with USP and FCC methods as well as those of the Cosmetic, Toiletry and Fragrance Association’s Compendium of Personal Care Ingredient Composition.

Our client-focused teams offer valuable guidance in personal care testing and the development of new products. We value our strategic partnerships and perform all work under strict confidentiality.

We deliver a complete suite of innovative personal care chemistry testing services including:

• Stability studies and storage
• Verification of sunscreens and preservative purity
• Testing of creams, lotions, shampoos, fragrances, oils and preservatives
• Limit of free ethylene oxide, 1,4 dioxide and propylene oxide
• Carbon chain distribution or fatty acid composition

Our specialized scientists respond to your specific needs and constraints, helping accelerate and streamline your processes from raw ingredients right through to finished product.

ICH Q6B guidelines specify the characterization of a biotechnological or biological product (which includes the determination of physicochemical properties, purity and impurities, biological activity and immunochemical properties) by appropriate techniques.

We provide a complete suite of support services to determine the purity, identity and potency of biological products and biosimilars including protein, peptide and oligonucleotide-based drug substance or drug product. Our services characterize:

• Identity: Mass spectrometry (ESI-Triple Quad (QTRAP), MALDI-TOF, ultra-high resolution Q-TOF), NMR (1D and 2D), IR, Raman, UV-Vis, protein sequence and composition
• Purity and impurity: LC (reversed phase, ion exchange, and size exclusion) electrophoresis (native/SDS-PAGE, isoelectric focusing)
• Potency: Ligand binding assays and functional assays

We provide a complete suite of expert structure elucidation techniques for proteins, peptides, oligonucleotides, PEGylated proteins and small molecule drugs, antibody-drug conjugates (ADCs) and other polymers:

• Mass spectrometry
  • Ultra-high resolution Q-TOF mass spectrometer for accurate identification of proteins, peptides, oligonucleotides, PEGylated proteins and small molecule drugs, ADCs and other polymers in extremely small quantities
  • De novo peptide sequencing and identification of modified sites using MS/MS
  • High-resolution MS for accurate determination of drug-to-antibody ratio and drug load distribution of ADCs

• NMR spectroscopy
  • Determination of the 3-D structures of proteins, peptides and oligonucleotides
  • NMR spectrometer equipped for liquid and solid state analysis, providing comprehensive 1-D and 2-D spectra data for identification and structure determination

• Single crystal structure determination of peptides

Services for single crystal screening and three-dimensional structure determination by X-ray diffraction

According to ICH Q6B guidelines, impurities in biological products can be classified as process-related or product-related. Process-related impurities include those that are derived from the manufacturing process (e.g., cell substrates, cell culture media components or downstream processing). Product-related impurities in the drug substance are molecular variants with properties different from those of the desired product formed during manufacture or storage.

To characterize these impurities, we offer a complete suite of analytical techniques for the isolation and characterization of process- and product-related impurities:

• Isolation and purification by LC: Reversed phase, ion exchange, size exclusion

Identification: Mass spectrometry (ESI-Triple Quad, MALDI-TOF, Q-TOF), NMR (1D and 2D), FTIR, Raman and UV-Vis spectroscopy, N-terminal Edman sequencing, LC-MS/MS de novo sequencing, peptide mapping, disulfide bond mapping, amino acid analysis

Changes in a manufacturing process, equipment or facilities can result in changes in a biologic that affect its safety and efficacy. We develop comparability protocols to reduce the risk of such changes by outlining strategies for comparing the properties of pre- and post-change materials.

Per ICH Q5E, we assess comparability between the pre- and post-change product by showing experimentally that the samples are highly similar in terms of physiochemical and biological characteristics, degradation profile, pharmacokinetics and immunogenicity.

Physiochemical characterizations, biological assays and stability degradation profiles of the drug product are the cornerstones of a comparability study. We offer comparability study support from analytical evaluation (identity, purity/impurity, high order structure) to biological characterization (ligand binding and functional assay).

Per the specifications outlined in ICH Q6B, we offer analytical services in support of protein drug development to determine physical and chemical instabilities at different stages. The molecular structure of protein is delicate and highly sensitive to environmental changes and stresses. Ensuring native-like higher order structure in a biologic is essential because the overall conformation defines the drug’s stability, biological activity, efficacy and safety.

We apply numerous techniques (e.g., freeze-drying and spray drying) for solid state protein formulation development and to tailor test to your specific needs.

Preformulation Screen

We evaluate the physical stability of protein in various formulation excipients such as ionic strength, buffers, pH, surfactants, sugars, salts, antioxidants and amino acids on the physicochemical properties of the protein.

• Gel permeation chromatography and size exclusion chromatography, coupled with a static-light-scattering detector, to detect and quantify protein aggregation
• Nano-DSC to monitor conformational stability of biologics in their formulations; detecting structural alterations (unfolding/aggregation) in a biologic in the form of a Tm (denaturation temperature) shift or a change in the shape of the endothermic peak (∆H and ∆Hv for domain and subunit organization)
• Dynamic light scattering (DLS) or quasi-elastic light scattering to evaluate the aggregation state; nondestructive DLS determines size distribution of particles in the diameter range of 1 nm to 2 µm

Lyophilization Process Development and Optimization

We offer small-scale lyophilization services to screen common excipients for protein stability.

• Protein formulation in compatible excipients based on the physicochemical properties of the protein
• Temperature-modulated differential scanning calorimetry to determine the glass transition temperature of the formulation in the frozen state (Tg’) and freeze-drying microscopy to determine the collapse temperature
• Optimal shelf temperatures and chamber pressures for primary and secondary drying
• Characterization of the finished lyophilized product using X-ray powder diffraction and polarized light microscopy to assess crystallinity; thermogravimetry and DSC for thermal properties; scanning electron microscopy for particle morphology; Karl Fischer titration for water content; dynamic vapor sorption/desorption for hygroscopicity testing and solid state NMR; FTIR and Raman spectroscopy for chemical and physical fingerprinting
• Evaluation of physical stability (unfolding/aggregation) of protein upon lyophilization by SEC, nano-DSC, DLS, CD and HPLC

Real-Time and Accelerated Stability Studies

Storage stability of proteins correlates with the degree of retention of native structure of proteins and the level of hydration during drying. Environmental conditions such as temperature, pH, ionic strength, oxygen and protease content can cause denaturation, aggregation, degradation and chemical modification (oxidation and deamidation). We offer advanced analytical methodologies for stability evaluation that ensure structural integrity and physicochemical identity.

• Physical stability assessment: Aggregation state evaluation by SEC and DLS, conformational change by nano-DSC and solid state characterization by various analytical techniques including XRPD, TG, DSC, SEM, SSNMR, FTIR and Raman

Chemical stability assessment: Ultra-high resolution Q-TOF mass spectrometer and solids/liquids NMR spectrometer in conjunction with techniques such as peptide mapping, MALDI-TOF MS, amino acid analysis and Edman N-terminal sequencing for accurate mass and primary sequence of proteins and peptides

Most biological pharmaceuticals such as proteins, peptides and oligonucleotides are supplied as aqueous solution or lyophilized solids. To date, insulin is the only biologic available in a crystalline formulation.

A crystalline formulation has some advantages over its amorphous counterpart, including high concentration and high purity: In the crystalline form, the protein molecules exist in the most concentrated form and retain an active conformation. Second, a crystalline formulation offers the possibility of controlled release because the dissolution rate in aqueous solution is low relative to the amorphous material. Third, crystalline material may offer greater physical and chemical stability than liquid solutions or the amorphous state due to higher purity, its more compact molecular arrangement and restricted molecular motion.

Our expert scientists offer crystallization screening using a variety of crystallization techniques. We conduct initial screening on a small scale using various vapor diffusion techniques (sitting drop, hanging drop, sandwich drop and capillary) and batch crystallization techniques (slow evaporation, fast evaporation and anti-solvent precipitation). We further optimize and scale up the conditions in which crystallization occurs. The batch crystallization process can also be applied to large-scale purification.

We also use these crystallization techniques for single crystal growth of proteins and peptides for 3-D structure determination.

The growing number of biologics advancing to market brings an increased demand for thorough characterization. To meet these needs, our scientists provide a complete suite of characterization capabilities. Unlike traditional small molecule drugs, biological products are inherently heterogeneous, so differences in molecular structure or the presence of impurities can dramatically change efficacy, immunogenicity or toxicity.

We also help you navigate critical regulatory guidances. The ICH defines guidelines regarding quality, specifications, stability, comparability and method validation in development activities concerning biological products. The guidance calls for inclusion of analytical methods for control of API as well as adventitious agents. It also specifies that the physicochemical and biological properties of biomolecules be defined, especially as they relate to manufacturing. Acceptance criteria are also recommended.

The guidance on specifications indicates that identity tests should be highly specific for the drug substance or drug product and should be based on unique aspects of its molecular structure and/or other specific properties. More than one test (physicochemical, biological and/or immunochemical) may be necessary to establish identity. Physicochemical characterization generally includes determination of the composition, physical properties and primary structure of the desired biological product. In some cases, information regarding a higher order structure may be obtained by appropriate physicochemical methodologies. The purity and impurities of biological products are usually estimated by a combination of methods (e.g., HPLC, UPLC and electrophoresis).

Stability tests are necessary, especially for protein and peptide drugs due to their structural complexity and instability. The most common chemical degradation mechanisms for peptides and proteins are deamidation and oxidation. The guidance on stability of peptides and proteins recommends tests of both chemical stability and biological activity.

We free up your resources, allowing you to concentrate on product development while we demonstrate compliance to regulatory requirements and guide your product to market.

Our experts bring years of experience in the pharmaceutical, cosmetic and consumer industries, and have handled a diverse and vast list of products and specifications. We also provide guidance to ensure your product receives the appropriate testing.

Facility

We are an FDA-regulated, DEA-licensed, ISO 17025 and ISTA-certified contract service provider to the pharmaceutical, medical device, personal and consumer product industries. We offer analytical services for the testing of materials, finished products, container and package systems that enable you to meet the required quality standards established by key regulatory agencies.

Our stand-alone testing facility is dedicated to analyzing raw materials through finished products. It meets strict requirements to ensure we conduct FDA-regulated, GMP tests and utilizes key pieces of equipment including world-class incubators, ovens and fume hoods.

Testing capabilities

Our experts conduct tests that include:

• USP <51> Antimicrobial Effectiveness Testing – A preservative effectiveness test that is required for developmental formulations through finished products stability
• USP <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests – Product safety testing is required to ensure that a product’s preparation complies with a preset specification for microbiological quality.
• USP <62> Microbiological Examination of Nonsterile Products – Tests for specified microorganisms and pathogens including S. aureus, P. aeruginosa, E. coli, Salmonella species, Clostridium species, fungal organisms and a qualitative MPN for bile-tolerant gram-negative bacteria
• USP <87> Biological Reactivity Tests, In Vitro
• USP <1231> Water for Pharmaceutical Purposes
• Standard Methods – For the Examination of Water and Wastewater

We ensure that your products are properly sterilized throughout your program and help demonstrate the control of your manufacturing processes so your product can be successfully released to market.

To determine the microbial load on the products, our experts perform bioburden/microbial enumeration testing (MET) on various pharmaceutical articles including:

• Raw materials
• Finished forms
• Medical devices
• Packages that are categorized as nonsterile

MET includes assessment of the physical characteristics and inherent antimicrobial properties of the product in question.

Bioburden Testing

Bioburden testing ensures that pre-sterilization microbial load is within the tolerance of the sterilization cycle, residuals after sterilization are at acceptable levels and your products are properly sterilized throughout the program.

Bioburden testing is also used during the release of your product to market in order to demonstrate that your manufacturing process remains in control. This testing includes enumeration by total aerobic microbial count and total yeast and mold count.

Regulatory bodies require monitoring of the bioburden load in products used for humans and animals to ensure product safety according to procedures outlined USP <61> and <62> guidelines:

• USP <61> An enumeration test, sometimes referred to as bioburden, that quantifies microorganisms in nonsterile products or raw materials
• USP <62> Testing for the presence or absence of specific organisms in a product, which can include Escherichia coli, Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella species, Clostridia species and bile tolerant gram negative bacteria

USP <61> and USP <62> testing provides harmonization to the European Pharmacopeia methods for testing nonsterile pharmaceuticals.

To conduct bioburden testing, we apply the following techniques:

• Membrane filtration method
• Standard plate count
• Pour plate method
• Most probable number
• Direct enrichment
• Membrane filtration enrichment

To ensure the quality of your parenteral drug formulations, medical devices, raw materials, excipients, water, water for injection and APIs, our experts offer testing for the detection and control of endotoxins.

Your tests are performed to USP <85> bacterial endotoxins test and USP <161> transfusion and infusion assemblies. Similar medical devices specify endotoxin testing requirements, including for medical devices with direct blood or cerebrospinal fluid contact.

Capabilities 

We perform endotoxin method validation on every product and/or formulation. Validation, or inhibition and enhancement (I/E) testing, ensures that the sample does not interfere with the method, which could lead to false positive or negative data.

Validation also ensures proper sensitivity, diluent selection and dilution factor.

Endotoxin limits are established based on formulation, dosage per hour, route of administration and average patient weight, but may also incorporate trending data as well as monograph specifications.

We perform antimicrobial effectiveness testing (AET) or preservative effectiveness testing to help evaluate your product’s ability to withstand microbial contamination during use. Our experts provide this testing for injections packaged in multiple-dose containers, as well as for products containing antimicrobial preservatives. We also test products such as aqueous-based, multiple-dose topical and oral dosage forms, and pharmaceutical dosage forms including otic, ophthalmic, irrigation, nasal and dialysis fluids.

This type of test is performed according to USP <51> Antimicrobial Effectiveness Testing, EP 5.1.3 Efficacy of Antimicrobial Preservation and CTFA Preservative Challenge Testing. Testing for the following microorganisms is required per USP <51>: Escherichia coli, Staphylococcus aureus, Candida albicans, Aspergillus brasiliensis and Pseudomonas aeruginosa.

We perform antimicrobial effectiveness testing for method suitability and for routine testing. Our capabilities for bioburden testing include:

• Membrane Filtration Method: A quantitative technique that isolates colonies of bacteria and fungi from a fluid sample using a membrane filter and vacuum
• Standard Plate Count/Pour Plate Method: Isolates bacteria and fungi by plating a sample preparation to a petri dish and adding nutrient agar that allows growth of any microorganisms present
• Spread Plate Method: Isolates bacteria and fungi by plating a sample preparation to a nutrient agar plate
• GMP-compliant stability chambers for storing your products, which we monitor for temperature and humidity

We provide microbiological population verification services through the assessment of biological indicators per USP <55>. Biological indicators are used in the validation, performance verification and/or with-use verification of cleaning and sterilization processes, such as steam sterilization, ethylene oxide sterilization and gamma irradiation. They typically contain a high concentration of bacterial endospores that are the most resistant to sterilization and are available in many formats corresponding to their use.

In order to meet the requirements of USP <55>, the population of biological indicators must be verified. This involves processing and/or suspending the indicator in a diluent, diluting it to the countable range and enumerating.

Probiotic Label Claim Verification

Probiotic products are typically labeled with a population concentration. As with nutritional supplements, vitamins and drugs, it is important to ensure that any product contains the specified or labeled range of a therapeutic substance.

Organism Verification

The organism or organisms present on the label that claim for a probiotic or biological indicator should be identified to ensure purity. Testing for microbial limits will also help ensure purity and safety.

To ensure the quality of your parenteral drug formulations, medical devices, raw materials, excipients, water, water for injection and APIs, our experts offer testing for the detection and control of endotoxins.

Your tests are performed to USP <85> Bacterial Endotoxins Test and USP <161> Transfusion and Infusion Assemblies and Similar Medical Devices specify endotoxin testing requirements, including for medical devices with direct blood or cerebrospinal fluid contact.

Capabilities 

We perform endotoxin method validation on every product and/or formulation. Validation, or inhibition and enhancement (I/E) testing, ensures that the sample does not interfere with the method, which could lead to false positive or negative data.

Validation also ensures proper sensitivity, diluent selection and dilution factor.

Endotoxin limits are established based on formulation, dosage per hour, route of administration and average patient weight, but may also incorporate trending data as well as monograph specifications.

We deliver expert services to test disinfectant and cleaning efficacy of critical areas, ensuring successful control of your environments in accordance with USP<1072>.

In addition to validating the cleaning process, we qualify the disinfectants and antiseptics implemented.

For your sanitizer or disinfectant efficacy study, we can also perform simulation studies, hard surface tests and tests under nominal conditions/procedures. Disinfectant validation may also include in vitro tests: a time kill study or suspension testing, coupon or carrier testing, environmental monitoring and in situ testing.

In designing your disinfectant efficacy validation or verification solution, our experts consider the following factors:

• Surfaces present in the critical area, including different conditions or types of the same material
• Each disinfectant and dilution to be challenged by a panel of representative organisms
• Testing for standard USP organisms: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis (spore), Candida albicans and Aspergillus brasiliensis
• Panel to include environmental isolates collected from environmental monitoring of the facility or critical area
• Expiration verification through the use of aged disinfectant preparations
• Neutralization of the disinfectant, e.g., suitability testing
• Recovery method evaluation or control
• Cleaning process overview and validation: Facility materials and environment, disinfectant preparation, cleaning procedure and contact time, facility surfaces, facility-specific bacteria and fungi

With our support, you can confidently implement environmental monitoring programs in cleanrooms, manufacturing plants, packaging facilities and testing laboratories.

We enable you to control microorganism levels in your manufacturing environments and minimize the bioburden on your products.

We provide environmental monitoring services to evaluate your cleaning and disinfection programs. Our experts help assess the microbial cleanliness of your manufacturing environment per USP <1116> Microbiological Evaluation of Clean Rooms and Other Controlled Environments.

We take air and surface samples during production to obtain a microbiological profile of the manufacturing environment and record additional observations of work practices during the survey. Our experts evaluate the data to determine any actions you can take to reduce or stabilize the bioburden of the medical product or production area.

Programs include viable and nonviable air monitoring, cleaning effectiveness, equipment monitoring, surface monitoring, disinfectant efficacy, gowning and personnel monitoring, compressed air testing, compressed gas testing and water system validation monitoring.

Risk assessment and program design

New facilities, new programs, construction areas, adjacent areas, post-construction areas and change control typically warrant a risk assessment and program design that may include evaluation of:

• Baseline bioburden and particulates (often including seasonal trending)
• Identification of organisms across the baseline sample
• Process, procedure and practice

Once we conduct a comprehensive evaluation, we recommend a program be implemented with a defined frequency and specifications established either by regulatory requirements or trending data.

We determine the microbiological quality of environmental water and water produced for pharmaceutical purposes to ensure the safety of your finished products and processes.

Critical enumeration of microorganisms and the assessment of the microbiological quality of water used in manufacturing are key performance indicators of your system control.

Our team performs water testing during purified water system installation as well as validation, performance verification and routine monitoring to evaluate whether your water systems are within acceptable levels of control. Feed water can also be monitored and controlled.

Capabilities

Bioburden testing includes the quantitation of microbes such as aerobic plate count, yeast/mold count, heterotrophic plate count, total coliforms, coli, Enterococci, Listeria and Pseudomonas aeruginosa. For water for injection, bacterial endotoxin testing is also required.

Our range of water testing services includes:

• Bioburden
• Total organic carbon (TOC)
• Conductivity
• Heavy metals testing
• Bacterial endotoxin testing

Physical properties of a molecular entity can vary greatly depending on the solid form (salt, cocrystal, amorphous dispersion or crystalline polymorph). By screening and selecting solid forms early in development, we provide the basis for consistent production and performance while reducing costs associated with toxicological bridging studies or further process development efforts. Optimization of available solid forms provides an opportunity to overcome physical property challenges or potential form control issues by identifying more promising alternatives.

We provide a complete suite of solid-form screening services to select the most appropriate solid forms for intermediates and drug substances. Sensitive to the different requirements of drug indication, stage of development, intended formulation and storage conditions, our experts customize investigations to identify the most appropriate forms for desired physical properties and controlled scale-up.

Phase Appropriate Crystallization Process Development

Our dedicated group of crystallization experts has a legacy of success in particle engineering and technology transfer. Experienced scientists and engineers offer a fit-for-purpose approach to crystallization processes adapted for each stage of pharmaceutical development. We take a quality by design approach to crystallization process development, aiming for the consistent preparation of batches with the desired purity, crystal form and particle properties. We enable reproducible and streamlined downstream processes, including filtration, drying, transfer and storage of the bulk drug substance, as well as critical performance attributes for drug product formulation and manufacturing.

Design of Crystallization Process

Solid form understanding and preliminary solubility data must be gathered to identify possible crystallization techniques and solvent systems for the design of a scalable process. Standard solution crystallization techniques include cooling, antisolvent addition, pH swing, reaction and evaporation. We collect metastable zone width information in systems of interest to determine suitable seeding conditions and control strategy. Online and offline monitoring during crystallization may also provide valuable insight into nucleation and growth of the crystals as well as the polymorphic form. Our scientists have access to specialized equipment for crystallization process development, including controlled laboratory reactors from 50 mL to 2 L, equipment for solubility and metastable zone width determination and in situ or at-line monitoring of crystal form, supersaturation, nucleation, particle size and morphology.

Process Analytical Technology and Quality by Design

Our scientists have access to process analytical technology equipment to allow development and optimization of crystallization using a quality by design approach:

• Solubility determination capability
  • Crystal16™
  • Solvent addition
  • Gravimetric
  • Equilibrium solubility with analysis of supernatant by UV-vis, HPLC or UPLC
• Controlled laboratory reactors from 50 mL to 2 L scale
  • Mettler Toledo EasyMax™ controlled lab reactors (50–100 mL)
  • Radleys Lara™ (100, 250, 500 mL, 1 L and 2 L)
• In situ and offline monitoring
  • pH
  • Mettler Toledo Turbidity Trb 8300
  • Kaiser Raman RXN3
  • Image analysis
• Filtration
  • Vacuum filtration
  • Agitated filter dryer (up to 2 L scale)
  • Centrifuge

Crystallization Optimization

We can design, optimize or troubleshoot your crystallization process for product purity, recovery or solids separation and isolation. Our experts provide you with an understanding of your process to reduce operational problems by means of:

• Polymorph investigations
• Control and measurement of impurities
• Kinetics of nucleation and growth
• Crystal size distribution measurement and modification
• Habit modification
• Filtration studies
• Drying investigations

Leverage our comprehensive polymorphism studies to ensure the safety and efficacy of your solid forms, enable IP and deliver critical data for your NDA filling.

Our experts investigate isolation and crystallization of your API in a number of solvents with different properties and under a variety of conditions. We  identify and characterize new solid forms (polymorph, hydrate, solvate) and to understand the relationship between them.

By applying our novel computational models, we collect high-quality data to develop a deep structural understanding of the solid forms present and predict properties including relative thermodynamic stability, habit, density and electron density.

Techniques

Based on the time and materials available, we offer a variety of screen types, which we tailor to your specific needs at any phase of development.

• Solvent-mediated screening
• Fast evaporation
• Slow evaporation
• Mechanical techniques
• Grinding
• Thermal techniques
• Computational pattern matching and TRIADS™ indexing analysis (U.S. Patents 7372941 and 8576985)

We use High-Throughput Screening (HTS) technologies to perform an increased number of crystallization experiments resulting a significant reduction in cost.

X-ray powder diffraction is the best first method to discriminate solid forms and provide critical data for property determination and structural exploration.

Biopharmaceutical properties such as pH-solubility profiles, ionizability and permeability are key parameters to assess performance of a drug substance and provide guidance regarding a compound’s classification system. Combined with physicochemical properties such as solubility, dissolution, hygroscopicity, crystallinity, stability (chemical, thermodynamic, solution) and bulk properties, we provide critical data for successful drug substance and drug product development and manufacture.

Curia provides a complete suite of state-of-the-art instrumentation and techniques to characterize physicochemical and biopharmaceutical properties. Our experts work with you to identify appropriate experimentation and interpret results for the selection of suitable forms.

• Foreign particulate identification