The development of antibody-drug conjugates (ADCs) typically involves using monoclonal antibodies (mAbs) “linked” to a cytotoxic drug and used as a specific targeting mechanism to deliver highly potent drugs to a surface antigen present only on tumor cells. Think of it as the biologics version of a smart bomb, with a targeting system able to change course and direction to deliver a cytotoxic payload only to cancer cells while avoiding collateral damage to the surrounding healthy tissue. ADCs were first introduced into healthcare treatment almost twenty-five years ago and have since seen approximately thirteen additional approvals by the FDA with a variety of indications, mostly in cancer therapy. The ADC market was estimated to be $9.8 billion in 2023 and speculated to reach $19.8 billion by 2028 (see here).
These “magic tools” of drug delivery, however, are not without their own unique set of side effects and/or problems, which is not surprising, given their complexity. Notably, due to their “construction,” the linker used to bind the drug and the antibody together can prematurely release the cytotoxic drug into the plasma, resulting in “off target” effects. In response, new modalities of linkers have been developed to lessen the potential for premature release. Other areas are being investigated to better refine the development of ADCs, such as new cytotoxic payloads and new conjugation methods. These next-generation versions of ADCs are contributing to more effective and efficient ADC drug delivery methods.
With innovation comes new challenges in manufacturing and analytical methodologies to develop and test these ADC compounds. ADCs have more than one active intermediate requiring multiple manufacturing steps, and often involve different CDMOs for the co-development of both small and large molecules. Each of these manufacturing processes comes with its own set of GMP challenges and CMC technologies. Analytical methodology requires specialized expertise, equipment, and methods to accommodate the unique molecular structures being employed in ADC manufacture, release, and stability testing.
By far, these issues are representative of not only developmental challenges but also regulatory obstacles requiring proper navigation through the development space. Lachman Consultants offers the knowledge and staff to help mitigate these challenges, whether it is CDMO certification, analytical method development and validation, or various stage FDA interactions and application review. If your firm is developing an ADC and is facing some challenges, Lachman can help! Reach out to us at LCS@LachmanConsultants.com for a free consultation.
