Human antibody (immunoglobulin)

The demand for manufacturing capacity of antibody-drug conjugates (ADCs), which includes a highly potent cytotoxic drug linked to a monoclonal antibody and have shown to be very effective and efficient in treatment of human diseases, including various cancers and hematological malignancies,  is rapidly growing.

Even so, a recent report published by ReportLinker demonstrates that in-house manufacturing of ADCs by pharmaceutical and biotechnology companies is rare. Discussions with senior manager in both the pharmaceutical and biotechnology industries reveals that around 70% of ADC manufacturing is currently outsourced to Contract Management Organizations (CMOs).  One the primarily reasons is that the complex nature of ADCs, requiring both clean room biologic and high containment cytotoxic facilities designed for safe handling and manipulation of very low Occupational Exposure Limit (OEL) compounds while maintaining aseptic conditions and GMP compliance.[1] 

The manufacturing of ADCs is still difficult to achieve and is accompanied with several known and unknown challenges. Furthermore, considering the fact that utilization rates are likely to be relatively low in the very near future, the capital investment needed for setting up specialized, high-containment biologic facilities may pose a prohibitive financial risk for some smaller pharmaceutical and biotechnology companies. But even the leading technology providers, including Seattle Genetics and ImmunoGen, depend, in part, on contract manufacturers.  And despite the fact that Roche, in October 2013, seemed to be among a few companies breaking the trend when it announced a CHF 190 Million ($ 210 Million) investment in building in-hoiuse ADC manufacturing capacity in Basel, Switzerland, as part of a larger investments in biopharmaceutical development capacity, outsourcing is likely to continue for at least the coming decade.[1][2]

MabPlex
ADC Bio
Lonza
Broadpharm
 

Contract Manufacturing
Over the last 5 years, the CMO market has changed dramatically, shifting from the manufacturing of blockbuster drugs to specialist care drugs. With increasing complexity of ADCs, there is a real opportunities for companies that are able to offer specialized, innovative, chemistries requiring skilled workers.

Biologics and highly potent APIs, includeing ADCs, are, in the next 5 years, projected to grow by more than 6 to 10% giving CMOs an incentive to truly invest in developing their unique capabilities and their specialized workforce. Successful CMOs will be recognized by their ability to deliver high-quality, customized manufacturing services designed to drive the performance of their customer’s end products. In addition to a strong workforce, offering differentiating technologies and services leveraging their unique capabilities in biologics and highly potent APIs is crucial.

The past 5 years has seen a surge in investments for facility expansions as well as mergers and acquisitions by a number of CMOs, including Lonza, Piramal, Carbogen-Amcis, Catalent, and others. [2]

In the past 24 months, for example, Lonza expanded it’s mammalian production capacity at its United Kingdom facility in Slough (Thames Valley technology corridor), Ajinomoto Althea created a new biological drug product manufacturing operations to include highly active materials such as ADCs in close proximity to the company’s operations in San Diego, CA, while Piramal confirmed that, following a UK £2.0 million investment to grow it’s manufacturing base at Grangemouth, Scotland, it is planning an US $ 10 million expansion of Coldstream Laboratories, its sterile injectable manufacturer the company purchased in early 2015.

One-stop-shop
The concept of on-stop-shop, is, as part of shaping the future, also gaining traction as CMOs are collaborating with one another in an effort to cater to the increasing demand and to streamline the manufacturing process under one umbrella. Although there are, to-date, only two approved and marketed antibody-drug conjugates, a rich and extensive pipeline presents a very big opportunity for the contract manufacturers, leading to a steadily growing market after suffering many years of lackluster growth.  The expectation is that by 2018 global revenues for CMOs are predicted to reach US $ 60 billion.

Emerging class of drugs
In their report, the authors of ReportLinker offer an extensive study of the contract manufacturing opportunity for the emerging class of antibody-drug conjugates. The report covers identifies CMOs active in this space, their capabilities with respect to the development and manufacturing of ADCs, available capacity for bio-conjugation, as an overview of  geographic location and spread of the facilities.

Increasing opportunity
With several drugs in the preclinical and clinical pipeline, the opportunity for contract manufacturers is likely to increase significantly. One of the key objectives of this report is to understand the future potential for CMOs in the ADC market.

Recent partnerships have, over the last five years, shown greater activity among CMOs, including developing new product manufacturing agreements, technology collaborations, as well as mergers and acquisitions. The increase is seen in the CMO investments to develop new and expand existing manufacturing facilities and  supporting facilities in order to ensure sufficient production capacity and safe handling of these compounds.

2015 and beyond
The base year for ReportLinker’s report, which provides short-mid term and long term market forecasts for the period until 2020 and 2020 – 2025, respectively,  is 2015.   The authors discuss, in detail, the key drivers behind the growth of the ADC contract manufacturing market, and present their research, analysis and insights backed by a comprehensive survey on ADC manufacturing capabilities of several CMOs.

In addition, the authors have interviewed a number of key stakeholders (from academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market as well  the future opportunities and challenges which must be considered for a more inclusive growth.

These were primarily designed to draw out the opinion of the major stakeholders on how the market will shape up across different regions and drug segments.

Finally, to add robustness to their forecast model, the report’s authors have provided three market scenarios which vary in terms of the overall ADC commercial sales and the likely cost of manufacturing. And while the focus of the report has been on forecasting the market over the coming ten years, the authors also provides an independent view on various technological and non-commercial trends emerging in the industry.

Partnerships
An analysis of available in-house and contract manufacturing of ADCs shows that only a few CMOs have capabilities to carry out all the different steps required in the manufacturing of ADCs.  While these full service providers are able to manufacturing different components of ADCs, as well as manufacturing of antibody, drug-linker, conjugation, fill/finish and other components involved in ADC production, the authors conclude that not all CMOs have a thorough experience with ADC, requiring additional investments or the development of partnership to create successful collaborations. But, they acknowledge that increased collaborations have helped the market reach its current growth trajectory.

In the last few years, Sigma-Aldrich’s SAFC® Custom Manufacturing Services business unit (now part of Merck Sigma) and Baxter BioPharma Solutions have, for example, partnered to manufacture and conduct all the steps of ADC manufacturing to cater to the customer needs.  In September 2014 the two companies announced their agreement to offer a combined approach for the development and production of ADC to simplify the supply chain and provide comprehensive, coordinated and collaborative services for the development, manufacturing, and testing of bulk drug substance and drug product. Earlier, Goodwin Biotechnology and Coldstream Laboratories (now part of Piramal) collaborated to act as full service providers of antibody-drug conjugates.

A paradigm shift
While, historically, biopharmaceutical manufacturers require large scale production capacity for large volume protein therapeutics needed to meet the need of large doses over long periods, new personalized and targeted therapies require much small batch production. Furthermore, as a result of the availability of these novel, more potent agents, including ADCs, the need for large batch production is decreasing.

This change reflects a paradigm shift in the industry. To maintaining desired quality attributes, reduce time to market, maintain cost effectiveness, and providing flexibility, demand for manufacturing capacity has, changed from traditional, large scale, manufacturing facilities containing multiple 10,000 L or larger cell culture bioreactors and supporting areas to specialized manufacturing required to develop and launch more agents aimed at multiple niche markets with considerable smaller patient populations. This change to more specialist care drugs is one of the most notable changes observed in the market.

Conclusions
Among the conclusions reached, the authors expect that brentuximab vedotin (Adcetris®; Seattle Genetics) and ado-trastuzumab emtansine (Kadcyla®, Genentech/Roche) the two commercially available ADCs,to start generating annual sales of close to US $ 1 billion in the near future. In addition to the agents, there are over 50 drug candidates in clinical development. And twenty-five percent of these drug candidates are in Phase II and Phase III development.

While Seattle Genetics and Genentech/Roche, with 7 and 6 ADCs in clinical development respectively, have the most developed portfolio of antibody-drug conjugates, relatively new entrants including Abzena, Mersana Therapeutics, Oxford BioTherapeutics, Philochem, Synthon and Zymeworks, are expected to provide a real push, both in terms of technology and innovation.

ReportLinker’s authors anticipate that the overall CMO market for the manufacturing of antibody-drug conjugates will to breach the US $ 1 billion mark in the coming decade. In fact, there is a strong belief in the market that existing CMO facilities for ADC manufacturing will require expansion to cater to the growing population of pipeline molecules.


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Last Editorial Review: February 21, 2016
Last Editorial Update: February 22, 2016

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