Client-Centric CMC Services in an Ever-Evolving Regulatory Landscape
Chemistry, manufacturing and controls (CMC) is a fundamental part of any biopharmaceutical product regulatory filing and is relevant to the whole product lifecycle, from drug candidate selection through post-approval and beyond. CMC maintains the connection in quality between the drug product used in clinical studies and the marketed drug that is made available to consumers.
Global manufacturers trust Avomeen’s expert scientists to provide industry-specific insight and thorough CMC consulting and lab services for the development and manufacturing of drug products through Phase II. Avomeen’s analytical and testing solutions support all phases of product development up to commercialization and beyond. Our consultative approach combines purposefully equipped labs, a dedicated team of scientists, and up-to-date regulatory knowledge. This ensures speed to market as our team works in partnership with our clients to expeditiously move therapeutics, drug products, and vaccines through clinical development, formulation, and manufacturing.
Comprehensive Chemistry, Manufacturing and Controls Support
Method Development & Validation – Analytical methods are developed to test a defined characteristic of a biopharmaceutical drug substance or drug product compared to established acceptance criteria. Method validation is the process of demonstrating that an analytical procedure is suitable for its intended purpose. Our blend of regulatory knowledge and scientific expertise ensures that the analytical methods we develop and validate can demonstrate that products meet FDA standards for identity, quality, safety, purity, and potency.
Q1/Q2 (Q3) Deformulation – Deformulation is a key part of generic biopharmaceutical drug formulation and the abbreviated new drug application (ANDA) process. Q1/Q2 refers to the assessment of inactive ingredients that is part of all ANDA filings, and Q3 similarity data may also be required for some complex ANDAs to confirm physicochemical similarity.
Characterization of Impurities – Impurity testing is integral to ensuring the purity, safety, and quality of drug substances and drug products. Avomeen offers a comprehensive suite of services to characterize impurities in biopharmaceutical drugs, including residual solvents, elemental degradants, leachants, and processing agents. Our scientists offer complete solutions that meet ICH Q3A, Q3B, Q3C, Q3D, and M7 guideline requirements for impurity characterization.
Extractables & Leachables (E&L Studies) – As part of biopharmaceutical regulatory submissions, an understanding of extractables and control of leachables is expected. Extractable and leachable (E&L) studies are critical to identifying and quantifying harmful impurities from container-closure systems, processing equipment, and packaging that could contaminate a drug product. With our consultative approach, skilled scientists will guide you through the process to access and profile your products’ extractables and leachables, all while meeting FDA regulations.
Elemental Impurities – From initial design to large-scale manufacturing, contaminants, impurities, and residuals can make their way into pharma and biopharma formulations throughout the drug development process. The presence of these impurities can affect the efficacy and safety of the final product and significantly delay time-to-market. Avomeen’s experienced pharmaceutical scientists deploy a variety of advanced tools to identify impurities, including ICP-MS, coupled with customized sample preparation techniques to demonstrate compliance with International Conference on Harmonization (ICH) and United States Pharmacopeia (USP) guidelines.
Stability Testing – Stability testing demonstrates how the quality of a biopharmaceutical drug varies over time when exposed to a variety of environmental factors including humidity, temperature, and in some cases, light. Our Ph.D.-led teams of chemists operate in a high compliance environment and are adept at taking on all aspects of product stability and ICH Q1A-F stability requirements, including characterization of degradants and stability data trending. FDA-compliant stability testing protocols help determine expiration dates, provide recommendations on storage conditions, and testing intervals with Bracketing and Matrixing Designs. Additionally, API degradation caused by light can be determined with photostability services per ICH Q1B.
Finished Product Batch Release Testing – Ensure the quality of biopharmaceutical drug products with GMP batch release testing, also known as lot release testing. Our team has a proven track record of success in developing, validating, and transferring sophisticated, complex, and challenging analytical methods for the purposes of batch release testing. Where other laboratories fail with unique APIs and challenging matrices, we succeed. Our experience and expertise extends to a range of substances, including active pharmaceutical ingredients (APIs), investigational medicinal products (IMPs), and finished drug products.
Raw Material Release Testing – Identity, purity, and quality must be established before any raw material can be used for manufacturing a pharmaceutical drug product, and all raw materials must meet the requirements outlined in the Code of Federal Regulations (CFR) 211.84. Our industry and regulatory experts offer comprehensive testing services to release raw materials per pharmacopeia (NF, USP, EP, and BP) and client-driven internal specifications.
Solid State Characterization – When in solid form, small molecule drug substances can exist in different molecular arrangements and/or conformations within their crystal structure. Understanding and selection of the optimal solid form is critical to biopharmaceutical drug development, as different physical properties can impact biopharmaceutical characteristics. Avomeen’s Ph.D.-led team of industry experts extend biopharmaceutical and therapeutic product lifecycles, while providing invaluable insight into the physical characteristics of your materials. A variety of experimental assessments are used to carry out solid-state characterization, including structural determination, thermal analysis, and solid-state analysis, as well as polymorph, co-crystal, and salt screening.
Compendial Testing – Compendial monograph (pharmacopeial) tests are standardized methods and specifications for biopharmaceutical raw materials and finished products. Testing and compliance to the standards detailed within compendial methods is a basic requirement for manufacturing release and distribution of drug products and biopharmaceutical ingredients around the world. At Avomeen, all compendial testing is performed in our stability and release testing labs per cGMP standards of 21 CFR 210 and CFR 211. Our technical team of CMC services experts has experience testing to a pharmacopeial monographs set by various regulatory bodies, including the US Pharmacopoeia-National Formulary (USP/NF), the European Pharmacopoeia (EP), and the British Pharmacopeoeia (BP).
Reference Standard Characterization & Management – Reference are essential for validating the quantitative and qualitative accuracy of analytical testing methods. The development, characterization and management of these highly purified and well-characterized compounds is critical. In some cases, there may be no established reference standards on record. Fortunately, FDA provides a roadmap for establishing a chemical as a reference standard in the absence of a readily available official source. Avomeen offers a complete reference standard management program that includes initial and continuous qualification of reference standards to meet the needs of small-, mid-, and large-sized companies, as well as those with a virtual or semi-virtual business model.
Cleaning Validation Support – cGMP regulations require product lines to be cleaned to a strict standard prior to manufacturing drugs from a different pharmaceutical formulation. Additionally, the processes used to clean the lines must be validated in advance of releasing pharmaceuticals to the market. Cleaning limits must be established in association with data inputs such as equipment surface areas, batch and dose sizes, and safety factors. Our consultative scientists have extensive experience developing and validating cleaning limit test methods and analyzing samples to ensure compliance with cleaning validation regulatory requirements.
We work with our partners to build comprehensive programs that incorporate the assays, methods, and technologies that will best help them reach their goals, including investing in and deploying a variety of advanced instrumentation, including:
- Agilent HPLC
- Agilent HPLC with DAD and Thermo-ESA Corona Charged Aerosol Detector
- Agilent HPLC with DAD and Polymer Labs PL/ELS ELSD
- UPLC with DAD & Fraction Collector
- Agilent GC-FID/TCD
- Agilent GC-MS/FID with Headspace Autosampler
- Ion Chromatography System
- Dionex Integrion RFIC System
- Waters Acquity UPLC with Xevo G2-S Quadrupole Time of Flight (QTOF)
- Thermo Finnigan LCQ Deca LC-MS
- Sciex HPLC + API LC-MS/MS
- Maldi Micro MX Mass Spectrometer
- Agilent Inductively Coupled Plasma Mass Spectrometer
- Agilent ICP-MS
- AB Sciex Triple Quadrupole API and Mass Spectrometers
Other Capital Instrumentation
- Evolution Dissolution Apparatus Systems
- Maurice-OBM Capillary Electrophoresis (CE)
- Perkin Elmer Spectrum FT-IR
- Spectrophotometer/ Colorimeter
- BioTek Epoch Microplate Reader
- Invitrogen Countess II Automated Cell Counter
- NANODROP UV-Vis Spectrophotometer
- Advanced® Micro-Osmometer
- Karl Fischer Titrators
- TA Instruments Differential Scanning Calorimetry
- TA Instruments TGA
- Sievers Laboratory TOC Analyzer
- Brookhaven ZetaPALS Zetasizer
- Malvern Mastersizer
- Franz Vertical Diffusion Cells Apparatus
- Caron Stability Chambers (Custom Settings)
- Caron Photostability Chambers
Comprehensive CMC Services and Solutions for a Variety of Drug Products
Solutions for a Variety of Drug Products Including:
- Generic Drugs
- Innovative Products
- Combination Products
- OTC Drugs
Regulatory Requirements & Filing Pathways Expertise
- IND (505 (b)(1) Pathway
- NDA (new drug application)
- BLA 351(a) Pathway (biologics license application)
- Biosimilar 351(k) Pathway (biosimilar biologics license application)
- NADA (new animal drug application)
- 505(b)(2) Pathway (new chemical entity)
- ANDA (505(j) Pathway (for generic products)
- OTC (monograph-based or IND-based)
Why Partner with Avomeen?
In addition to a litany of tests and capabilities, Avomeen has the resources and know-how to provide comprehensive CMC support throughout the entire product lifecycle.
Regardless of your challenges, Avomeen is the partner you need to advance your therapeutic and biopharmaceutical product regulatory submissions. So, no matter where you are within the drug development pipeline, give us a call and see how our CMC consulting services can transform your boldest goals into real solutions.