Thursday, December 4, 2014

Goodwin Biotechnology-- Your Single Source Solution™ for Cytotoxic ADCs

Together with our collaborative partner, Coldstream Labs, GoodwinBiotechnology has the experience, expertise, and capability to develop and manufacture highly potent CADCs from proof of concept through to non-clinical and clinical use, late stage as well as commercial manufacturing.

Goodwin Biotechnology is a full-service, customer-focused and integrated contract services provider with a pioneering focus on the development and manufacturing of Cytotoxic Antibody Drug Conjugates (CADCs) from cell line development or exploratory proof-of-concept through process development, scale up,  and cGMP manufacturing. 

Goodwin Biotechnology leverages over 10 years of bioconjugation experience and expertise which complements our more than 20-year history in the development and manufacturing of mammalian cell culture-derived monoclonal antibodies, recombinant proteins and vaccines, making us one of the most experienced and stable contract manufacturing organizations (CMOs) in the world. Moreover, our global customer base which includes clients from North America, Europe as well as Asia, consists of companies ranging from academic institutions and biotechnology startup firms to large, established, multinational biopharmaceutical companies. Recognizing the challenges of manufacturing complex molecules such as CADCs, Goodwin Biotechnology will help to formulate a strategic approach to your project with an emphasis on critical development, manufacturing, quality, regulatory and characterization considerations.

Whether you have already developed a conjugation process and simply require a technology transfer or need development of a new conjugation process, Goodwin Biotechnology will partner with you to develop and/or optimize your Cytotoxic Antibody Drug Conjugate (CADC) using a risk-based Quality by Design (QbD) approach.

Selection of an appropriate linker is important, and Goodwin Biotechnology demonstrates tremendous flexibility in this regard.  We can:
·         Utilize your proprietary linker, or
·         Employ our proprietary and license-free Linker Technologies, including
·         Non-cleavable, thioether-based SteadFastTM Linker Technology, or
·         Cleavable, disulfide- or hydrazone-based FlexReleaseTM Linker Technology
·         Collaborate with our partners to design and synthesize novel, cleavable linkers based on peptide or other appropriate linkages. 

For more information on our unique SteadFast™ or FlexRelease™ Linker Technologies, please fill out the form below.

Moreover, selection of an appropriate cytotoxic payload to which the target cancer cell demonstrates susceptibility is critical, and Goodwin Biotechnology will help to evaluate a payload of the appropriate potency and specificity under the Safebridge or Merck classification systems (e.g., protein toxin, cytotoxic peptide or small molecule cancer drug).

Goodwin Biotechnology can work with cytotoxic payloads up to Safebridge Level 3 within our own facilities (e.g., doxorubicin or methotrexate); however, for ADCs utilizing highly potent cytotoxic payloads (e.g., maytansine, auristatin, DM4, or tubulysin) requiring a Safebridge level 4 / Merck level 5 facility, GBI has collaborated with Coldstream Laboratories where we seamlessly execute all conjugation processes within Coldstream’s high-containment facilities, from proof-of-concept through late-stage clinical trials and large-scale cGMP manufacturing or commercial products.

Rest assured, whether we work onsite at GBI or offsite at our partner’s facility, we will develop at the earliest stages a scalable, GMP-compliant, economical and efficient process that is designed to manufacture your CADC product in an expedient manner and meet all appropriate quality requirements relative to safety, purity, identity, potency and immunogenicity.

When developing Antibody Drug Conjugates, added consideration must be given to issues of aggregation, solubility, precipitation, product integrity & activity as well as reaction by-products that often play a larger role in bioconjugates as compared to unconjugated proteins.  With more than a  decade of experience, we can  help overcome these technical and compliance challenges by selecting the appropriate solvents, optimizing reaction times, and utilizing appropriate purification processes (e.g., TFF, chromatography, and other filtration processes) that are linearly scalable for large-scale GMP manufacturing and compliant with regulatory guidelines

Further, at an early stage during development, Goodwin Biotechnology will perform product pre-formulation with limited stability studies to determine the appropriate buffer pH, conductivity, excipients, and storage temperatures that confer long-term product stability.  In addition to pre-formulation development, our collaborative partner,
Coldstream Laboratories, can develop lyophilized formulations that are based on robust and cost-efficient processes. Their rapid-response formulation team has experience in screening effective combinations of solvents (both aqueous and non-aqueous), buffers, bulking agents, and lyo/cryo-protectants. This experience leads to a robust final product that has low residual moisture/solvent, forms a solid and attractive cake, reconstitutes readily and completely, and resists physical and chemical degradation.

Coldstream Laboratories offers clinical and commercial formulation development as well as ISO 5-compliant liquid and lyophilized Fill & Finish in a variety of container / closure systems ranging from tens to thousands of vials depending on your needs.
Comprehensive analytical characterization is a critical element of developing and manufacturing Cytotoxic Antibody Drug Conjugates (CADCs), and Goodwin Biotechnology will perform assay tech transfer and verification or develop analytical methods to fully characterize your CADC relative to potency, purity, identity, safety, quality, and Drug to Antibody Ratio (DAR). Analytical methods must encompass characterization of the CADC’s Critical Quality Attributes (CQA) and quantification of product-related impurities as well as process-related impurities. This includes determining the percentages of:

·         Unreacted antibody, linker, and cytotoxic payload
·         Aggregates and cleaved antibody fragments
·         Unreacted antibody-linker OR linker-payload
·         Reaction by-products

We will work with you to develop a strategy to identify regulatory pathways and gain regulatory approval of your Antibody Drug Conjugate (ADC) in accordance with the requirements of the relevant agency (i.e., FDA, EMEA, and others).

Examples of our Quality and Regulatory expertise

·         FDA inspected and commercial  manufacturing facility
·         Risk based Quality by Design (QbD) approach towards ADC development
·         CMC support for INDs and BLAs
·         Toxin cleaning procedures and handling

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