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Publications & Presentations

Physical and Chemical Stability of Antibody Drug Conjugates: Current Status

Philip L. Ross and Janet L. Wolfe. Journal of Pharmaceutical Sciences. February 2016, Volume 105, Issue 2, Pages 391–397.

Antibody drug conjugates (ADCs) are an emerging class of chemotherapeutic cancer treatment agents that combine the targeting specificity of antibodies with the efficient cell-killing potential of cytotoxic drugs. Unlike their protein and small-molecule therapeutic counterparts, the stability and degradation properties of ADCs are relatively unknown. Theoretically, ADC stability could be governed by properties and processes stemming from both the antibody and the linker-toxin chemistry. Recently, systematic studies of intrinsic ADC molecule stability have been presented in the primary literature. As there are burgeoning industrial and academic efforts aimed at developing optimized conjugation chemistries and antibody engineering approaches for next-generation ADCs, it is important to capture the current state of understanding of ADC stability. In this minireview, we discuss aspects of physical and chemical stability of ADCs gathered from a survey of the literature and illustrate how investigations into stability enable the development of more effective ADC molecules for the future.


Rational ADC formulation design as a tool to prevent chemical and physical instabilities

Protein and Antibody Engineering Summit European Summit (PEGS Europe)

Lisbon, Portugal
November 2-6, 2015

AbstractADCs have unique attributes that are affected by the nature of the component parts as well as by the processing, storage and administration conditions to which they are exposed. An understanding is required of the multiple degradation pathways that an ADC can undergo, after which the formulation can be rationally designed.  Such an approach requires an array of biophysical and analytical characterization techniques, and yields a de-risked development path that minimizes the timeline to clinical testing. A case study will be presented of formulation approaches that mitigate aggregation and chemical degradation pathways.



Chemical and physical stability considerations for antibody-drug conjugates

Protein and Engineering Summit

Boston, MA
October 22-23, 2015

Abstract:  As ADCs become a mature therapeutic modality, there is an increasing need to fully understand factors that contribute to the chemical and physical stability of these molecules.  There are specific aspects of chemical stability of ADCs that set them apart from protein or small molecule therapeutics.  The physical stability of ADCs may bear some relation to the underlying antibody scaffold, but there are specific attributes of ADCs that require attention in order to maintain or optimize physical stability.  This presentation will highlight several examples that illustrate how the chemical and physical stability of ADCs must be addressed in a somewhat different manner than antibody therapeutics.



Short Course. Physicochemical and Biophysical Characterization of Antibody Drug Conjugates

Protein and Engineering Summit
Boston, MA
May 7, 2015

Antibody drug conjugates are complex, heterogeneous products that require a wide array of characterization tools to support manufacturing, storage and administration. It is critical to have meaningful analytical and biophysical tools early in development to rationally design the manufacturing process and to demonstrate control over the process and product. An effective analytical toolkit will enable the identification and elimination of liabilities, resulting in significant time and cost savings. Attendees will learn analytical and biophysical characterization best practices for this rapidly growing therapeutic class, including:

-- Intrinsic properties of ADCs
-- Extrinsic forces to which an ADC is exposed over the lifetime of the product that will influence the types of analyses required
-- Analytical techniques used in QC assays
-- Biophysical techniques for characterization
-- Identification of degradation pathways for the intact ADC and for its component parts
-- State-of-the art technologies


Formulation Development of Antibody Drug Conjugates.

Biopharmaceutical Development and Production Week
Huntington Beach, CA
March 30-April 2, 2015

ADCs have unique attributes that are affected by the nature of the component parts: the antibody, the linker and the toxin. The attributes are affected by the formulation, the process parameters, and the storage conditions. Effective formulation development strategies are based upon a molecular understanding of the ADC: aggregates, charge variants, DAR, conjugation site, free drug, various degradation pathways. Development of ADCs requires an array of analytical and biophysical techniques that are used to identify attributes that could have a clinical impact.


Formulation and Route of Administration.

Washington, DC,
February 19, 2015

Training Course in Neurotherapeutics Discovery and Development


Defining Critical Quality Attributes of Antibody Drug Conjugates.

AAPS Annual Meeting
San Diego, CA
November 2-6, 2014

Pharmaceutical Development of ADCs Short Course.


ADC "Developability:" Critical quality attributes inform formulation and process development.

CHI Bioprocessing Summit
Boston, MA
August 18-22, 2014

ADCs have unique critical quality attributes (CQAs) that are affected by the nature of the component parts: the antibody, the linker and the toxin. The CQAs are also strongly affected by the formulation, the process parameters, and the storage conditions. Effective formulation and process development strategies are based upon a molecular understanding of ADC CQAs: aggregates, charge variants, drug antibody ratio, conjugation site, free drug. Development of these complex molecules requires an array of analytical and biophysical techniques that are used to identify attributes that could have a clinical impact. In this short course, the attendee will learn:

-- Characterization tools to inform rational ADC development
-- Intrinsic molecular attributes: consideration of the mAb, linker and payload
-- Degradation pathways of ADCs
-- Extrinsic factors that affect CQAs: formulation and process design


Key Attributes and Considerations for Developing Formulations for an ADC.

BDP Week, San Diego, CA
March 24-27, 2014

The physical and chemical stability of ADCs present significant challenges during the development of ADCs. There are multiple routes of chemical degradation and the aggregation pathways are highly complex. An understanding of these pathways enables streamlined development, process scale-up and manufacturing. The attributes that influence formulation critical quality attributes will be discussed.


Conjugation Site Heterogeneity Causes Variable Electrostatic Properties in Fc Conjugates.

Nicholas J. Boylan, Wen Zhou, Robert J. Proos, Thomas J. Tolbert, Janet L. Wolfe, and Jennifer S. Laurence. Bioconjugate Chemistry. 2013 24 (6), 1008-1016.

Wolfe Laboratories is conducting exciting research in the area of antibody-drug conjugates (ADCs), a rapidly growing area of therapeutic development. The Wolfe Laboratories team recently published research that could help unravel the problem of varying charge properties of ADCs – a drug-development hurdle that causes high heterogeneity and limits the widespread use of ADCs. This research is part of Wolfe Laboratories’ ongoing investigation of the molecular causes for the physical and chemical destabilization of ADCs, as well as its development of approaches to stabilize these important molecules. For more information on this research, please take a look at the abstract.


Finding A Chemistry Postdoc Position In Industry, Chemical and Engineering News

Featuring Wolfe Laboratories,  September 10, 2012, Volume 90 (37), pp. 48 - 50

"Wolfe Laboratories, a contract research organization based in Watertown, Mass., continues to expand its program, according to Janet Wolfe, the firm’s chief executive officer. The company is now recruiting to fill a postdoc position that will involve a collaboration with Merck..."


Opportunities Along The Atlantic: Smaller firms are recruiting chemists to help tap new markets and cultivate groundbreaking technologies, Chemical and Engineering News

Featuring Wolfe Laboratories,  August 20, 2012, Volume 90 (34), pp. 61 - 63

"...Wolfe Laboratories is in the midst of hiring Ph.D. scientists in pharmaceutical chemistry, organic chemistry, biochemistry, or chemical engineering with two or more years of experience in drug development from the postdiscovery phase to the initial clinical trials phase, according to Margarita Hunter, the company’s associate director of marketing."


Quality Prospects: Drug developers are bolstering their quality management teams in response to a more rigorous regulatory climate, Chemical and Engineering News

Featuring Wolfe Laboratories, August 15, 2011, Volume 89 (33), pp. 40 - 43

…Wolfe Laboratories has been “vigorously expanding our services for the last few years to cover various aspects of drug development regulated under Good Manufacturing Practices and GoodLaboratory Practices,” says Verona Outerbridge, the company’s manager for business development and QA.  Wolfe is in the process of increasing its quality staff, which currently includes seven employees responsible for QC and three dedicated to QA.


Increasing R&D Productivity: Effectively Implementing Biopharma's Strategy

By Dr. Janet Wolfe, President and Founder, Wolfe Laboratories, 10 January 2011

..."the industry as a whole has embarked on a tripartite strategy: access innovation through external partnerships, pursue rare and under-treated diseases, and target emerging markets as a significant source of revenue."


PharmaVoice Top 100 Entrepreneurs - Dr. Janet Wolfe Predicting Trends

Featuring, Dr. Janet Wolfe, President and Founder, Wolfe Laboratories, July / August 2010

"From early in her career, Janet Wolfe, Ph.D., has been adept at identifying industry trends. When her family moved to the Boston area in 1999, she recognized the abundance of emerging biotech and pharmaceutical companies and foresaw high demand for experienced pharmaceutical chemists. She rented a 2,000-square-foot facility in Watertown, Mass., and formed Wolfe Laboratories."


Aseptic Filling Adjusting to New Paradigm - Complex and Sensitive Drugs Necessitate High-Tech Manufacturing Operations

Featuring, Dr. Michael Frid, Principal Scientist, Wolfe Laboratories, 1 April 2010

"Aseptic filling—the final step before packaging parenteral small molecule and biotherapeutic drugs—represents one of the most technologically innovative and dynamic areas of downstream operations."


Hundreds of Students and Volunteers Join Statewide Biotechnology Job Shadow Day

"More than 350 Massachusetts high school students will spend their day shadowing biotechnology professionals as part of their first-ever statewide Biotechnology Job Shadow Day."


Small Businesses Step Into Spot Light - Wolfe Laboratories Named Eastern Regional Finalist

"These seven small businesses were named regional finalists for the U.S. Chamber’s Dream Big: Small Business of the Year Award, sponsored by Sam’s Club®. One of them will receive the award during America’s Small Business Summit 2010 in Washington, D.C., May 17—19. The award recognizes a company for demonstrating exemplary business practices in the areas of staff training and motivation, community involvement, customer service, and business and financial planning."

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Wolfe Laboratories Integrated ADME and CMC Technology Platform

"At Wolfe Laboratories, we believe that integration of critical path drug development activities allows us to help our clients rapidly advance de-risked molecules from discovery into the clinic. ADME, CMC, and Drug Product Manufacturing are essential drug development functions that, if done right, can form the foundation of a highly effective program. Many companies treat these critical path activities as items to be checked off a list, rather than using them strategically to de-risk their drug discovery and development programs." Read moreView case studies.


Wolfe Laboratories on Wikipedia

"Wolfe Laboratories, Inc. (WLI) is a contract research organization (CRO) headquartered  in Watertown, Massachusetts. It provides research and development services as well as GLP analytical services for products in late discovery phase through early clinical phases of drug development. It serves clients in New England, the US, and internationally."


Flexibility is the Name of the Game for CROs, Genetic Engineering and Biotechnology News

Featuring, Janet Wolfe, Ph.D., President, Wolfe Laboratories, 15 June 2008

“Wolfe Laboratories is … ‘a bootstrap operation,’ founded nine years ago without any outside investors. [Janet Wolfe] described her company as a niche organization serving “one-compound companies,” mostly in the Boston area. “I focus on biotechs and pharmas that have raised at least $15 million in venture capital…when a molecule is nominated we take it all the way to Phase I, with involvement in critical path activities.”


Regulations Still Driving Stability Testing, Genetic Engineering and Biotechnology News

Featuring, John Augustine, Ph.D., Principal Scientist, Wolfe Laboratories, 1 Apr 2008

...“By the preformulation stage, it may already be too late to set up a stability study,” observes John Augustine, Ph.D., principal scientist at Wolfe Laboratories…


A Brief Introduction to Extractable's & Leachables: Or, Is There Something Extra in My Drug Product?

By Nicole Damour-Krilla, Project Manager, Wolfe Laboratories, 9 Nov 2007

..."as the API and its formulation are optimized, so should the storage conditions, which include the container-closure system... (that) should guarantee the protection, compatibility, safety, and performance of the drug product."


Dose Recovery: Identification of a Problem and its Resolution

By Dr. Nicolas S. Mourier, Principal Scientist, Wolfe Laboratories, 12 Sep 2007

..."compatibility study with these diluents and administration sets from various providers can reveal losses in dose recovery when the test article is evaluated for up to 48 hours at the targeted high and low concentrations."


On Pre-Formulation and Formulation: Defining the Universe of Discourse

By Dr. Michael Frid, Principal Scientist, Wolfe Laboratories, 5 May 2007

..."pre-formulation refers to the physicochemical characterization of a compound and formulation refers to the development of a customized dosage form for a specific administration route."