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Emerging Trends in Single-Use Technology in the Manufacturing of Antibody-Drug Conjugates

Single-use technology, designed for the manufacturing of biopharmaceutical products, has made major inroads over the last 30 years. First introduced in the late 1970s in the form of disposable capsules and a range of filters, single-use technologies were revolutionized in the late 2000s with the introduction of single-use 2D and 3D process containers and filter assemblies for mixing and storage systems. Today, these technologies have been adopted across the upstream manufacturing process, downstream purification and fill-finish of entire classes of biologic drugs.

The adoption of single-use technology is especially growing in the development and manufacturing of biologics and complex drugs like Antibody-drug Conjugates (ADCs).

Antibody-drug conjugates
ADCs are highly potent biopharmaceutical drugs designed as a targeted therapy in the treatment of cancer. They are highly hazardous materials, often with occupational exposure limits (OEL) below 100ng/M³/8Hr work day.

The acute potency of ADCs creates a significant risk to personnel involved with the various manufacturing stages. The accepted method to counter the risk of exposure to ADCs is the implementation of so-called barrier isolation systems. These systems are recognized as the highest level of current containment technology, creating both respiratory and dermal protection.

While the use of glass or stainless-steel legacy systems may effectively protect operators, significant equipment decontamination is required. Since most ADCs are produced on a small (production) run/campaign with manufacturing typically taking days rather than months, the cleaning validation burden associated with a hard-shell glass or stainless-steel isolator can be an issue.

Alternative to traditional technology
“Single-use technologies are an alternative to traditional glass or stainless-steel manufacturing with the key difference in their materials of construction. Glass and stainless-steel equipment have decades of historical data and, as a result, their use is well characterized,” noted Karen Green, product manager for single-use assemblies at MilliporeSigma.

“Single-use systems are commonly composed of polymeric materials, which are not as well-known or characterized for biologics processing. These differences result in different approaches to validation and qualification,” she added.

Figure 1.0 A typical ADC process work flow. The input mAb is prepared into reaction conditions by simple dilution or through buffer exchange by ultrafiltration/diafiltration (UF/DF), a very economical, high-yield and robust separation process. In the processing equipment, the antibody will be further modified, then conjugated with the drug linker to form the crude ADC.

In the manufacturing of highly complex active pharmaceutical ingredients (APIs) such as ADCs, single-use technologies offer specific benefits in the upstream manufacturing and production of monoclonal antibodies (mAbs) and downstream bioconjugation.

For example, single-use technology enables faster process changeover and facility flexibility that is not possible when traditional equipment is used.

“Since each single-use system is pre-sterilized and used only once, there is no need to sterilize or clean systems between batches, saving time and enabling manufacturers to produce multiple products within the same facility. Furthermore, single-use systems are often mobile, allowing them to be moved within the facility as needed, enabling additional facility flexibility,” explained Mary Robinette, principal project engineer at MilliporeSigma.

Contract development and manufacturing organizations
According to various reports, 70-80% of the manufacturing of ADCs is outsourced to contract development and manufacturing organizations (CDMOs).[1]

“Due to [this] increased outsourcing pattern, CDMOs entertain many different types of ADCs. The use of single-use technology by CDMOs will help speed up the product change over time, avoiding time spent in establishing cleaning methods for each product that is produced, and eliminating upfront investment for expensive capital equipment such as reactors for each product,” said Gang Yao, Ph.D., principal scientist, process & analytical development at MilliporeSigma.

“In the end, customers benefit from lower manufacturing costs and speed to market. The faster turnover will result in more batches made to meet the commercial demand,” he added.

Implementation of single-use technology
Single-use technologies have advanced in several ways over the past decade. Their materials of construction are better known and have established leachables and extractables profiles, and manufacturing techniques have evolved leading to cleaner and more robust films.
Due to these advancements, the adoption rate of single-use has steadily increased across the biopharmaceutical industry, including ADC manufacturing. However, ADC manufacturers will need to be assured of solvent compatibility with bag liners and other single-use components since the manufacturing of ADCs often involves either dimethyl sulfoxide (DMSO) or dimethylacetamide (DMA) for the conjugation process.

They also will need to trust that the potential for a leak during the conjugation process is extremely low and that they can successfully scale from a smaller development scale to large-scale GMP production.

Single-use technology suppliers, like MilliporeSigma, have recognized these concerns and have demonstrated that the materials in single-use technologies are indeed compatible with two commonly used solvents (DMSO and DMA) at the temperatures and duration typically used for ADC processing.

Addressing the aggressive conditions used during bioconjugation to ensure compatibility with the polymeric materials used in single-use assemblies and understanding extractables and leachables under these conditions are vital. MilliporeSigma provides supporting data to ensure that the use of solvent during the manufacturing process will not negatively impact the conjugate by demonstrating solvent compatibility as well as sharing representative leachable and extractable data.

MilliporeSigma also has demonstrated that small-scale development batches can be successfully scaled up to large-scale GMP batches using a completely single-use process, guaranteeing operator safety at all steps in the manufacturing. In this single-use process, the fluid contact materials do not change, only the size of the components of the process assemblies. “However, operator safety becomes very critical with the use of more potent linker payloads that typically demonstrate IC50 values in the low-to-mid picomolar range,” Yao added.

Mobius® FlexReady Solution with Smart Flexware™ Assemblies for Chromatography and TFF
Mobius® Mixer
Mobius® Single-use Bioreactors
Pellicon® Capsules with Ultracel® Membrane

Tangential flow filtration
Tangential flow filtration (TFF) is a common unit operation in ADC manufacturing and enables concentration and exchange to pre-formulation buffer.[2]

The presence of toxic linker-payloads following conjugation presents challenges in traditional TFF operations. The scale of TFF also can be a challenge.

“MilliporeSigma has developed a completely enclosed single-use TFF capsule. This device is shipped gamma sterilized with RO (reverse osmosis) water, which reduces flushing requirements and enables faster batch turnaround while utilizing the same Ultracel 30 kDa membrane found in our traditional flat-sheet devices,” noted Nicholas Landry, group product manager ultrafiltration at MilliporeSigma.

“The device was engineered with operator safety and containment in ADC processes as design principles,” he added.

Upstream and downstream processing
While single-use technology has generally been used in upstream processing in the manufacturing of mAbs, the technology is now also available in downstream bioconjugation.

One of the major benefits of single-use technology in downstream processing is bioburden control. Single-use technology offers a more closed processing opportunity compared to traditional glass or stainless-steel reactors, thus reducing the opportunities for bioburden growth.

Another significant benefit of single-use technology is that there is no cross-contamination from inefficient cleaning, allowing faster turnover between process changeovers in a biopharmaceutical manufacturing facility, while at the same time, reducing cleaning validation requirements.

In the final verdict, single-use technology has proven, compared to traditional methods, to be a flexible, cost-effective and efficient alternative that provides improved safety. There is no cross-contamination from inefficient cleaning and no cleaning required between batches, resulting in a quicker turnover of the facility.

[1] Roots Analysis, Antibody Drug Conjugates Market (2nd Edition), 2014 – 2024.
[2] Czapkowski B, Steen J, et al. “Trial of High Efficiency TFF Capsule Prototype for ADC Purification,” ADC Review, April 12, 2017. [Article]

Last Editorial Review: November 20, 2018

Featured Image: Scientists in Laboratory. Courtesy: © 2010 – 2018 Fotolia. Used with permission.

Copyright © 2018 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


Evolution of Antibody-Drug Manufacturing

Antibody-drug Conjugates (ADCs) have evolved since the initial approval of gemtuzumab ozogamicin (Mylotarg®) in 2000, with respect to conjugation, linker and toxin chemistries and processing. With the current availability of 4 commercially approved drugs and approximately 80 programs in various clinical trials, there has been a significant interest in simplifying the complex supply chain.

With approximately 80% of the programs outsourced to Contract Development and Manufacturing Organizations (CDMOs), a transparent and integrated supply chain is critical for the success of ADC projects.

This white paper will describe how chemistry and manufacturing have evolved over the past 10 years globally and how MilliporeSigma, as a CDMO, has adapted to these changes to meet customer’s needs.

Register to download this free white paper

Learn more about:

  • how ADC manufacturing has evolved over the past decade
  • the challenges that this evolution implies
  • why the success of ADC projects are increasing tied to an integrated supply chain

Last Editorial Review: October 1, 2018

Featured Image: Scientist at MilliporeSigma Courtesy: © 2017 – 2018. Fotolia Used with permission.

Copyright © 2017 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


Lonza Expands Manufacturing Capacity for ADC Payloads

Lonza, a specialty contract development and manufacturing (CDMO) partner to the biopharma industry, will add new highly potent API (HPAPI) manufacturing suites at its site in Visp, Switzerland. The expanded capacity is for the specific support of antibody-drug conjugate (ADC) payload manufacturing.

By leveraging the company’s more than 100-year experience in chemistry, biopharmaceuticals and small molecule drug process development and scale-up, Lonza as developed a reputation in manufacturing and support of both clinical development and commercial licensing of antibody-drug conjugates (ADCs).

The expansion is based on a tailored business agreement with a major biopharmaceutical partner that ensures ADC payload supply continuity and flexibility at reduced cost of goods

This latest expansion includes two new manufacturing suites. These new suites enable handling of a variety of highly potent products with occupational exposure levels down to 1ng/m3 and strengthen the overall bioconjugation capabilities of the company.

Strategic decision
The expansion underlines the strategic position of antibody-drug conjugates in the Lonza Pharma & Biotech portfolio, with the company developing and producing all components of this increasingly important cancer treatment: cytotoxic payloads, antibodies and the required linkers.

The first of the two new HPAPI suites specifically supports a global biopharmaceutical partner by securing the long-term supply of highly potent ADC payloads.

The second suite will be available to other customers for similar HPAPI and payload development and manufacturing programs. The expansion also increases Lonza’s capabilities in providing fully scalable HPAPI and ADC solutions from lab to commercialization, which supports the accelerated timelines that many drug programs in this category require.

“By ensuring critical supply for the treatment of cancer patients, we are supporting one of our global partners in the oncology field,” said Maurits Janssen, Head of Commercial Development of the API Business Unit at Lonza Pharma & Biotech.

“Oncology continues to be the leading indication in biopharma and the main driver for bioconjugates. We continue to increase capabilities and capacity to meet the HPAPI development and manufacturing needs of our partners,” Janssen added.

Lonza is an established partner in developing and manufacturing HPAPI, with more than 20 years’ experience in safely progressing more than 30 products from early-stage work to late-stage clinical or commercialization. The company has the capabilities in place to safely handle HPAPIs to exposure levels down to 100ng/m3 across all manufacturing scales. These new suites will extend the options for companies developing APIs with even higher potencies.

“Our customers developing highly potent medicines need a partner whom they can trust to handle these toxic substances and to deliver in sync with their needs, whether for clinical or commercial supply,” said Gordon Bates, President Chemical Division at Lonza Pharma & Biotech.

“Combined with our expertise in biologics development, manufacturing, bioconjugation and sterile fill/finish, this new capability will offer further solutions for companies developing complex therapies,” Bates concluded.

Future of ADCs
The expansion confirms Lonza’s belief in the growing global therapeutic potential of ADCs which is, according to experts expected to grow to US $ 4bn by 2023, with double digit approvals within 3-years.

As part of this growth, novel payloads that target tumor-initiating cells on third generation antibody-drug conjugates or ADCs could come to market in the next couple of years. Driven by a healthy late stage pipeline, experts confirm that they expect the market for antibody-drug conjugates to expand at around 19% compounded annual growth rate (CAGR) between 2017 and 2030.[1]

These predictions are based on a new analysis published in the 2018 edition of the CPhI Annual Report – the complete findings of which were released earlier this month at CPhI Worldwide in Madrid, Spain, the global pharmaceutical event held October 9 – 11, 2018.[1]

Lonza’s HPAPI and ADC payload expansion, which is, in part, based on these expectations, is expected to be on-line by the end of 2019.

Disclosure: Lonza is one of the underwriting sponsors of ADC Review | Journal of Antibody-drug Conjugates.

Last Editorial Review: October 26, 2018

Featured Image: Lonza, Visp, Switzerland. Courtesy: © 2010 – 2018 Lonza, Visp, Switzerland. Used with permission.

Copyright © 2018 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


Benefitting from the Worldwide Supply Chain in the development of Antibody-drug Conjugates

Timing is everything.

Just over a decade ago, the pharmaceutical industry and R&D in China was dominated by generics and plagued with insufficient technical capacity and fewer investments at the initial stage of novel drug development.

Although China’s entry in the global pharmaceutical R&D industry started relatively late, substantial government support and a thriving economy, has changed the industry. In recent years, the country, as a whole, has achieved colossal success in building a modern industry.

China’s success is, in large part, the result of the countries Thousand Talent program, a 2008 government initiative targeting Chinese-born academics and workers who trained overseas – in the United States and Europe – and encouraging them to ‘come home’ with promises of grants and tax breaks.

In addition, the Chinese government has increased funding focused on graduating large numbers of university-trained Chinese scientists, which, in turn, helped the growth of venture capital and private equity funds that can directly invest in Chinese biopharmaceutical industries.

And the results of these targeted ‘investments’ have been impressive.

Combined with a burgeoning middle-class and rapidly-aging society, China presents vast opportunities for R&D, making the country an important innovator of pharmaceutical products. Managing a worldwide supply chain, in 2017, China invested approximately US $13.2 billion in medical and pharmaceutical R&D. This accounts for 8.9% of the total global medical and pharmaceutical R&D investment in the same period.

But with the enhancement of R&D, the strengthening of the regulatory framework and the perfection of clinical trial data of audits and inspections, R&D spending is expected to continue to increase.

A report published by Chisult Insight showed that China’s pharmaceutical R&D spending is expected grow to US $29.2 billion in 2021, representing 18.3% of the total amount of the global pharmaceutical R&D in that year.

Over the last decade there has been a growing number of Chinese contract development and manufacturing organizations (CDMO), such as MabPlex International (Yantai 264006, Shandong, China), that offer integrated, end-to-end services and open-innovation platforms to support pharmaceutical R&D and manufacturing for both small and large molecules.

From Generics to Innovative drugs
Leading Chinese pharmaceutical companies, historically focusing on the manufacturing of generics, are now investing in, and building, capabilities designed to develop and manufacture new and innovative drugs.

Their intent is to draw on the specific needs of Chinese patient’s needs, while, at the same time, capitalizing on knowledge from other markets, including Europe and the United States.

“Although China’ is the world’s second largest pharmaceutical market after the United States, some of the most effective modern medicines are not yet available.”

This approach is further supported by a group of innovative biotech companies founded over the past five years that focus on addressing global unmet medical needs.

According to health-care information company IQVIA, in 2017 China was the world’s second-largest national pharmaceutical market worth $122.6 billion. China is also the biggest emerging market for pharmaceuticals with growth expected to reach $145 billion to $175 billion by 2022.

Turning point
As a result, today, the biotechnology industry in China is at a turning point, with many key elements in place for innovation: an educational system churning out doctorates and strong basic research, substantial financial backing from both private investors and public sectors, regulations that are becoming globally harmonized, a changed legal environment designed to effectively secure Intellectual Property (IP) rights – which are among the most valuable resources for pharmaceutical and biotech companies – and a vibrant group of entrepreneurial leaders with ambitions for China and abroad.

Unmet medical needs
Western pharmaceutical and biotechnology companies, both in the United States and Europe, interested in working with Chinese biotechnology and life science industries, find a country facing significant unmet medical needs — particularly in cancer, neurology and diabetes — and a rapidly aging, often medically naïve (untreated) population. This, in turn, makes China unique for clinical trials.

Although China is the world’s second largest pharmaceutical market after the United States, some of the most effective modern medicines are not yet available.

Of 42 anti-cancer drugs approved globally in the past five years, for example, only four are currently available in China. With reforms on the way, this is expected to change rapidly.

Recent regulatory changes bring imported drugs to China more quickly, and local biotechnology and pharmaceutical are racing to develop novel, advanced, therapeutics for both the domestic and global markets.

Attractive for R&D
A generally low-cost base, a large pool of highly qualified research subjects, increased scientific capabilities, local industry’s knowledge, a general lack of regulatory and cultural impediments often found in other countries and insight into the country’s growing drug markets have made China an attractive country for R&D.

And following the implementation of comprehensive government reforms in the regulation of drug development and clinical trials, the country has become even more attractive.

In 2015 the Chinese government reformed the China Food and Drug Administration’s (CFDA) review and approval system for drugs and medical devices. These reforms have had a profound impact on the entire healthcare industry in China, affecting both Chinese and foreign companies pursuing development and registration of pharmaceutical drugs and medical devices in China. The CFDA reforms initiated less than 3 years ago and the regulatory changes these reforms have brought are expected to catalyze the pharmaceutical industry in China.

Since the reform began, the CFDA has issued hundreds of new policies, guidelines, and draft opinions to optimize the regulatory landscape. The results – progress – in reforming the system has been significant.

For example:

  • The backlog of 22,000 drug applications reported in August 2015 have been to about 8,000 by the end of 2016;
  • A total of seventeen batches of 227 applications, including both Clinical Trial Applications (CTAs) and New Drug Applications, were granted priority review status by June 2017.
  • Since the beginning of the reform, 10 provinces are now running Drug Marketing Authorization Holder pilots.
  • The number of reviewers at the Center for Drug Evaluation has increased from about 150 in 2015 to 600 by the end of 2016. It is expected that this number of reviewers will further grow in the years ahead.
  • An expert-committee system that taps into external expertise to support review and approval of innovative drugs is being established.

However, regulatory changes are ongoing in China. And while the impact of new reorganizations, such as the establishment in March 2018 of the new State Market Regulatory Administration (SMRA) and State Drug Administration (SDA), which will replace the CFDSA, are still unknown, the results will be far-reaching.

Global Clinical trials
The current regulatory approval for pharmaceutical agents in China is, in many cases, based on clinical trials that have been carried out in the country. But in order to be designated Investigational New Drug a Chinese legal entity must submit the drug registration application. And since clinical trial applications are also considered to be drug registration applications, overseas drug manufacturers in the United States or Europe interested in conducting clinical trials in China without legal representation in the country, must apply for product registration through an agent with professional knowledge and familiarity with Chinese laws and regulations.

In contrast to many other countries, the CFDA is also responsible for authorizing the import of Intellectual Properties (IPs). Prior to the import or manufacture of medicinal products protected by IPs, the CFDA needs to issue an import drug license for each individual IP.
This has a direct impact on the development of clinical trials. For example, for multi-center trials, documentation demonstrating that the clinical trial’s imported drugs have been prepared according to good manufacturing practices (GMPs) should be included in the application dossier.

The CFDA will, however, prioritize the review and approval of foreign innovative drugs, such as novel, investigational antibody-drug conjugates (ADCs) that are either manufactured in China, manufactured at a facility in the United States or European Union and are simultaneously under review for marketing authorization by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

In addition, the drug testing institute must conduct sample testing and specifications verification of the IP in order to issue a Certificate of Analysis as part of the CFDA’s approval requirements for all registered drugs.
Finally, as part of the approval to conduct clinical trials, China has a decentralized process for the ethical review of clinical trial applications. As part of this process, approvals are required from institutional level ethics committees for each trial site. This process is implemented through a three-tiered framework consisting of national ethics committees, provincial ethics committees, and institutional level ethics committees.
In contrast, United States (US) has a decentralized process for the ethics review of clinical trials in which the sponsor is required to obtain approval from an institutional level ethics committee, referred to as institutional review boards (IRBs), for each study.

Growing Interest
Many of the new regulations and requirements as well as new requirements yet to be implemented, have also contributed to the global pharmaceutical industry’s interest in conducting clinical trials in China. This has directly led an increased interest by US and European companies to work with a Chinese contract research organization (CRO) and contract (development) and manufacturing organizations (C(D)MO) such as MabPlex International.

The regulatory environment has, no doubt, boosted China’s ambitions plans to be a primary market for CROs and CDMOs. Most of the top 20 multinational pharmaceutical companies have been expanding their footprint in China by setting up R&D facilities through various legal structures. And global biopharmaceutical companies including Bristol-Myers Squibb (BMS), Pfizer, Roche, GlaxoSmithKline (GSK), Johnson & Johnson and Novo Nordisk are developing partnerships with Chinese companies.

While this approach mitigates traditional development risks, it also leverages local efficiencies, allowing global biopharmaceutical companies to add operational value due to familiarity with the market and regulatory requirements. In turn, this leads to shortened approval times and reduced development costs.

Made in China 2025
Growth in the Chinese biopharmaceutical industry is also expected as a result of a recent designation of biotech, in addition to other industries like robotics, aircraft, and electric cars, as one of the targeted industries in which the country wants to achieve an independent major position in by 2025.

Currently, China has ambitions for exporting generic medication around the globe. This ambition is evidenced by the growing number of generic drugs approved by regulatory agents in the United States and Europe.

This growth has been quite impressive. In 2017, Chinese pharmaceuticals obtained U.S. Food and Drug Administration approvals for 38 generic drugs, up from 22 such approvals in 2016.

Innovative drugs
However, in addition to becoming a manufacturing hub for generic drugs, China has also ambitions to develop and manufacture novel, innovative, pharmaceutical agents, as is evidenced by the development of antibody-drug conjugates (ADCs).

Today, antibody-drug conjugates are among the most complex drugs available. By combining an antibody with a cytotoxic payload, these drugs are directly targeting cancer cells, while, at the same time, leaving healthy cells alone.

The complexity is evidenced by the fact that since 2000, when the first ADC was approved in the United States, only 3 other antibody-drug conjugates have been approved, while more than 150 investigational agents have been or are currently in a clinical development program.

In an article published in the July 2018 edition of the International Immunopharmacology, researchers and scientists from RemeGen (Yantai 264006, Shandong, China) and MabPlex International, RemeGen’s development and manufacturing partner, confirmed the development of novel treatment options for B-cell lymphoma, one of the most refractory tumors.
Jointly established by Rongchang and Professor Fang Jianmin, RemeGen has developed a novel antibody-drug conjugate called RC48. In September 2015 this investigational agent became the first ADC in China to be approved by CFDA for inclusion in clinical trials.
RC48 is mainly used for the treatment of HER2 over-expression in gastric cancer, lung cancer, breast cancer, ovarian cancer, and bladder cancer.

Among the growing CDMOs in China is MabPlex International. Based in Yantai, a port city in Shandong province, China, and founded in 2013, the company specializes in the development and GMP manufacturing of recombinant proteins, antibody therapeutics and antibody-drug conjugates for its global customers.

From its inception, the company was designed to aide Western pharmaceutical companies, especially companies focusing on the development of innovative drugs, especially complex agents like antibody-drug conjugates or ADC. To accomplish the goal of attracting foreign clients, the company is establishing a track record by working with Chinese biotechnology companies to ‘win over’ these Western companies. And while some of MabPlex’ Chinese clients are looking to develop and manufacture drugs for the Chinese market, other companies are intently focusing on the development of complex, novel drugs to supply Western markets.

Multinational collaboration
Partnerships between Western pharmaceutical companies and Chinese CDMOs – to develop novel, innovative, drugs, has been rapidly growing.

These partnerships may take various forms, each with their own challenges, risks and benefits. One option includes a licensing agreement. Other options may include co-development or a joint venture.

With the tremendous advantages made by China’s industrial advances and progress made over the last decade, US and European companies can greatly benefit from developing these partnerships with Chinese companies

This is especially so in the development of novel, innovative, pharmaceutical agents.

To take advantage of the options, we will address the unique position of China in the global biopharmaceutical industry and the benefits working with Chinese R&D may bring to Western pharmaceutical companies, like MabPlex International in a two-part webinar.

This webinar series “Drug Development in China: What you Need to Know,” will include a discussion of important steps in bio manufacturing, research & development and drug development in China and a discussion of challenges and treats, trends in biopharmaceutical manufacturing, clinical trials and regulatory issues. A discussion of the regulatory reforms, which includes the transition of the CFDA to a new State Market Regulatory Administration (SMRA) and a new State Drug Administration (SDA) will also be included.

¹In March 2018, China established the State Market Regulatory Administration (SMRA), which will take on the responsibilities of the China Food and Drug Administration (CFDA) and several other government entities. The SMRA’s State Drug Administration will replace the CFDA. However, regulating the life sciences and healthcare space in particular, the restructuring also establishes a new State Drug Administration (SDA) which will be supervised by the SAMR. The reorganization acknowledges that the regulation of drugs, medical devices and cosmetics products still requires a highly specialized and dedicated government agency. The new SDA will maintain its own branches at the provincial level and leave the post-approval enforcement duties at the lower municipal and county levels to the consolidated SAMR branches. The new agency is expected to become one of the most   powerful market regulators to address the ever-mounting concerns about drug and food safety, protection of intellectual property and product quality issues in general.

²This webinar will also include the latest (available) updates regarding the ongoing regulatory reforms in China, which includes the transition of the CFDA to a new State Market Regulatory Administration (SMRA). Although information about SAMR’s restructuring and appointments, as well as any new policy goals and initiatives are expected to be released in due time, it is yet unknown whether the SAMR and the new State Drug Administration (SDA) which will be supervised by the SAMR, will change direction from the course set by the CFDA or continue to implement the previous CFDA reform initiatives. The reorganization may might delay actual implementation of previously announced initiatives.

Last Editorial Review: October 9, 2018

Featured Image: Photo by Hanny Naibaho on Unsplash


ADC Biotechnology Invests in New Bioconjugation Facility in North Wales, United Kingdom

UK-based ADC Biotechnology has secured investment for the construction of an $11 million* bioconjugation facility at its new site in Deeside, North Wales, UK.

The specialist antibody-drug conjugate contract services company with proprietary conjugation technology designed to overcome process and aggregation challenges during the development of new antibody-drug conjugates,

Photo 1.0: ADC Bio, Deeside, North Wales, UK

The new 6,500 m2 facility – scheduled to be operational by December 2018 – is expected to support manufacturing in all clinical phases and small-scale commercial production of antibody-drug conjugates. The new facility includes GMP production suites equipped with vessels of 10 up to a few hundred liters for batch sizes from 100 grams up to a kilo. The integrated facility is also expected to complement ADC Biotechnology’s long established technical services business that provides small scale R&D through to preclinical testing, with three on site laboratories and analytical testing capabilities.

‘Lock-Release’ technology
The company’s move into clinical and commercial ADC manufacturing is particularly significant as it already boasts a strong pipeline of customers – thanks to its patented ‘Lock-Release’ technology and the extensive experience of its senior scientists.

The aggregation control platform is currently used by over 20 customers, including a number of ‘big pharma’ as well as smaller biotechnology companies. The ‘Lock-Release’ technology results in fast, simple and robust conjugation processes with the potential to eliminate several process steps while, at the same time, enhancing product quality.

This process is expected to help overcome aggregation challenges from the more complex, potent and hydrophobic payloads increasingly coming through discovery and development. The ADC Biotechnology technology immobilizes protein elements, keeping them separated up to the point they are conjugated – ensuring that much cleaner drug products are ultimately released and that the quality and yield of highly aggregated systems are managed in one single step. The technology will also be available for licensing and sub-licensing in the future.

“We already have confirmation that many of our existing customers will use the facility for clinical development and we anticipate adding a number of the new targets entering clinical development from customers in the USA and Europe – especially in light of the added value we can provide through Lock-Release. For many of the newer types of payload this could well be the difference between a viable product and not,” noted Charlie Johnson, Chief Executive Officer of ADC Biotechnology.

The purpose-built, dual stream bioconjugation facility will provide a suite of capabilities ranging from R&D technical services, quality control, QA, warehousing, and process development through to manufacturing – all of which will occupy just 50% of the unit’s footprint. Consequently, ADC Bio will have free capacity to upscale quickly from early clinical phases into late phase and commercial manufacturing within the same footprint at the new facility.

Subsequent phases are planned for 2018 and beyond and will add further capacity for large scale clinical and commercial, and potentially, dosage form production (fill/finish).

“We are already preparing for future phases of development and the medium-term manufacturing pipeline for the business looks extremely strong. But longer term, we also have a lot of USPs – as a standalone site with patented Lock-Release technology – which makes us extremely attractive.” added Johnson.

ADC Biotechnology’s senior management and scientific team have decades of professional experience of developing ADCs both at ADC Bio and at rival CDMOs. Several of the company’s senior management were pivotal to the development and commercialization of Adcetris – the world’s first approved ADC. And, the company is already an integral part of the growing North West pharmaceutical manufacturing hub.

Last Editorial Review: September 25, 2017

Featured Image: science laboratory test tubes. Courtesy: © 2017. Fotolia. Used with permission. Photo 1.0: ADC Bio, Deeside, North Wales, UK. © 2017. ADC Bio. Used with permission.

Copyright © 2017 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


Evolving CMC Analytical Techniques for Biopharmaceuticals

1.0 Abstract
During the (early) preclinical drug development process as well as manufacturing of biopharmaceutical (protein) products, analysis and characterization are crucial in gaining a better understanding of the physical and chemical properties of various materials. These properties can have an impact on the manufacturability as well as the performance, potential for metabolism, stability and appearance of a specific medicinal product. Hence, properly characterizing these products is essential for a drug candidate to move from drug development to regulatory approval and, finally, the clinic.

In recent years, complex biopharmaceutical drugs and biologics have evolved into mainstream therapeutics. The manufacturing of these compounds, including monoclonal antibodies, bispecifics, antibody-drug conjugates (ADCs), recombinant and other therapeutic proteins, require extensive analytical and comprehensive characterization using a variety of techniques, including non-compendial, and sometimes an intricate quality control methodology, to confirm manufacturing consistency and product quality.

Because biopharmaceuticals and biologics exhibit highly diverse structures and broad biological activities, a study of these agents is a relatively complex process requiring sophisticated analytical techniques. Furthermore, in addition to these complexities, regulatory expectations to better understand product impurities and degradants in biopharmaceutical products continue to increase.

As a result, many drug developers may find that their current global chemistry, manufacturing, and control (CMC) systems are quickly becoming obsolete. Consequently, new, highly sensitive and specific technologies are becoming the new normal.

Keywords: Biopharmaceutical analysis, Characterization, Protein therapeutics, Bioanalytical methods, Structure and function, Physical and Chemical properties

2.0 New Analytical Approaches
The field of monoclonal antibodies, launched with Köhler and Milstein’s initial study published in 1975 of a method to produce fully intact murine IgG antibodies, has created a new area of the development of novel medicinal products. [1] In the more than three decades since the initial development of monoclonal antibodies, chimerization, humanization and fully human antibody technology followed. [2]

Subsequent to the growth of antibody-based products, new technologies have emerged for creating modified forms of antibodies, including antibody fragments, antibody-drug conjugates or ADCs as well as bi- and multi-specific antibodies.

In the development of these next-generation medicinal compounds, a better understanding of currently approved ADCs and novel site-specific bio-conjugation technologies is required. For example, a better analytical understanding of the structure-activity relationship accelerates the discovery and development of the next-generation ADCs with defined and homogeneous compositions.

Analytical methods and characterization for novel biopharmaceuticals and biologics involve complex, multi-faceted procedures stretching from early (pre-) clinical drug discovery to clinical development, regulatory approval and, finally, market entry.

Most of this work takes place during the early development phase, and is vital to help understand the influence of process changes, measured against an established reference standard.

3.0 Protein Therapeutics
Biopharmaceutical therapeutics are inherently challenging to characterize because of their complexity and natural heterogeneity. Therefore, appropriate and complete analysis ensures meaningful and reliable characterization, and provides the data required to satisfy regulatory requirements concerning product identity, (im)purity, concentration, potency, stability, safety and overall quality.

Methods used to characterize primary and higher-order structures (including techniques to determine protein sequence, posttranslational modifications, folding and aggregation) and protein concentration (including amino acid analysis, intrinsic protein absorbance and colorimetric methods) are vital to avoid aberrant results for key attributes that could, potentially, raise quality issues.

In addition, characterization and analysis of biopharmaceutical proteins also involves product- and process-related determination of impurities, which may compromise the safety of the protein therapeutics. This includes various assays (including bioassays and noncell-based binding assays) for determining the functional activity of proteins, which may be indicative of potency.

Overall, a complete approach to characterization helps developers to be confident that their product meets regulatory requirements as well as product quality and safety standards.

4.0 Changing Technologies
While spectrophotometric analyses of proteins are commonly used, there may be a number of important reasons to change analytical methods and characterization techniques.[a]

The reasons may include:

  1. New techniques may allow for better characterization, making it possible to follow the stability of specific molecules and proteins, as well as contribute to deeper understanding of them. New techniques may include imaging, capillary-electrophoresis, ultra-high-resolution mass spectrometry, micro-flow imaging (MFI), etc.; (Figure 1.0)
  2. Improved technologies to replace legacy methods. Examples include using ultra-high-performance liquid chromatography (UHPLC), a relatively new technique giving new possibilities in liquid chromatography, instead of high-performance liquid chromatography (HPLC) and Capillary Western (WES), a quantitative western blot produced by a protein simple, which offers increased precision and specificity versus ELISA; (Table 1.0)
  3. Formulation and process changes may occur in the early stages of drug development. Even through Clinical Trial phase I and phase II, there may be formulation or process changes, which may require additional or new analytical methods;
  4. There may an interfering compound within the formulation. One example is the use of surfactants[b], such as Polysorbate 80[c] (also known as PS80) which may interfere with the reverse-phase method. To be certain about stability, when observing new degradants, it may be required to use a new method that will resolve and quantify the new analytes;
  5. There are specific regulatory requirements that apply to approved products, including the expectation of periodic method assessment for improvement;
  6. Many techniques allow for strategic business decisions, resulting in high throughput with low costs. This largely depends on how many lots and stability studies are necessary. In turn, this may directly impact the costs associated with the regulatory approval process of products being developed.

Figure 1.0 A number of recent methods developed in the past years allowing scientists to look at antibodies much more closely include ultra-high resolution mass spectrometry (UHR-MS), multiple reaction monitoring (MRM), mass spectrometry, ultra-performance liquid chromatography (UPLC)[d] analysis of glycans (both by MS and HBLC fluorescence), microfluid imaging analysis and automated Western (WES).
5.0 Regulatory Implications
The regulatory process established by the U.S. Food and Drug Administration (FDA) requires that each New Drug Applications (NDA) and Abbreviated New Drug Application (ANDA) includes the analytical procedures necessary to ensure the identity, strength, quality, purity and potency of the drug substance and drug product. [3][4] Furthermore, each Therapeutic Biologic Application (BLA) needs to include a full description of the manufacturing process. This includes analytical procedures that demonstrate that the manufactured product meets prescribed standards of identity, quality, safety, purity and potency. [5]

The analytical procedures and methods validation for drugs and biologics, Guidance for Industry, states that, over the life cycle of a medicinal product, new information (e.g., a better understanding of product characteristics) may warrant the development and validation of a new or alternative analytical method. [6]

But analytical methods should not be considered to be “locked down” or validated once clinical trial phase I or phase II is reached. To fully understand the biopharmaceutical products involved, the FDA requires scientists to consider new or alternative analytical technologies, even after completion of the drug approval process.

The FDA also requires that drug developers and manufacturers periodically evaluate the appropriateness of an analytical method and consider new or alternative methods. To make this process simpler and more robust, and in anticipation of life cycle changes in the analytical process, an appropriate number of drug samples should be archived to allow for comparative studies. These samples must not only be put away for stability studies, but a reasonable number of samples should be archived at the proper temperature (typically at -80 degrees for a biopharmaceutical sample) to be used for crossover and comparability studies. This is critical to smoothing the pathway for change from one analytical method to another. [6]

6.0 Regulatory Reporting Requirements
Establishing a regulatory framework, the FDA sets “safety reporting requirements for human drugs and biological products” that include mandatory reporting of any change in analytical methodology, and describes—among other things—a developer’s responsibilities for reviewing information relevant to the safety of an investigational drug and their responsibilities for notifying FDA. These reporting guidelines cover minor, medium and major changes. (See: Table 2.0)

6.1 Minor Changes
Minor changes are those within the “validated change of the analytical method.” For example, when a validated chromatography method for a column temperature range of 10° to 40° change from a nominal of 30° to 35°, this would be considered to be a minor change. While this change can be submitted as part of the annual report, it is still required that the applicant reports the change to the agency. [8]

The Guideline for Industry detailing the requirements for the annual report stipulates that properly reporting post-approval manufacturing changes must be made in compliance with current Good Manufacturing Practice (cGMP). [9]

6.2 Moderate Changes
At the moderate level, the validated range is exceeded in certain parameters. Such a change may have an adverse effect on the identity, strength, quality, purity or potency of the drug product. Using chromatography as an example, this could be a change in mobile phase from acetonitrile to methanol, or a change in the actual gradient of a method. Such a change has more stringent requirements and required validation of this new method in additional comparability studies.

6.3 Major Changes
Major changes include modifications that establish a new analytical method, eliminate a current method (substituting one method for another rather than adding a new method), or delete or change the acceptance criteria for a stability protocol.

At the major level, there are substantial changes to the analytical method. For example, a major change includes switching from UV detection to mass spec (MS-) detection. Such a change must be validated with a formal, highly statistical comparability study designed to show any differences, or lack thereof.

In case of a major change, developers are also required to submit and receive FDA approval of a supplemental application to the original NDA or ANDA. In what is known as a Prior Approval Supplement (PAS), a major change needs to be reported and include a detailed description of the proposed change, which products were involved, a description of the new method, the validation protocols and data, a description of the changes to evaluate the effect of the change, a comparability report, a description of the statistical method of evaluation and a final study report. [8][9]

While a PAS is generally required for approved drugs, it also sets expectations for early-phase products. Although they are not covered under formal CFR regulations, the FDA does, in fact, expect at least a similar study to be performed when a drug is in clinical trial phase I, II or III.

7.0 Comparability Study
The comparability process is critical. The FDA requires that a manufacturer carefully assess manufacturing changes and evaluate the product resulting from these changes for comparability to the pre-existing product. In such a case, the goal is to show that a new analytical method is superior to the original method. [10]

Figure 2.0: Numerous new analytical approaches and characterization methodologies have emerged that are designed to (better) analyze biopharmaceuticals, allowing scientists to look at monoclonal antibodies much more closely. The FDA expects that applicants use novel methods in lieu of older methods. [Click here for table]
Based on the guideline for industry, determinations of product comparability may be based on chemical, physical and biological assays and, in some cases, other nonclinical data. This requires referring to archived samples from historical batches, and whether those are included in the Investigational New Drug (IND) submission, clinical or registration batches. [10]

This is a critical part of the process, because developers need to show that a new method is more sensitive or selective, and is therefore detecting and quantifying impurities or degradants that were always present, but not seen by the current (existing) method and, as a result of a change of methodology, can now be better monitored.

8.0 Comparability Design
A well-planned comparability design will assess the effect of CMC changes, allowing the FDA to determine if a specified change can be reported in a category lower than the category for the same change. Appropriate samples should be included, allowing a comparison of the ability of the new and original method to detect relevant product variants and degradation. This approach provides sufficient information for the FDA to determine whether the potential for an adverse effect on the product can be adequately evaluated. [11] [12]

To be adequate, the number of batches should be statistically relevant. The guidance to industry emphasizes the use of a trained statistician. The reason is that, while the FDA recognizes that a comparability design is less complicated than a clinical trial, it requires a statistician to design a robust program clearly showing differences between methods. [11]

9.0 Concerns
There are a number of concerns associated with the development and the implementation of new methods designed to replace a current (existing) method. The biggest question is whether the results of the analytical methods will be different.

In general, the expectation is that by changing analytical methods, there is indeed a fairly high probability of getting different results. Hence, if there is a change to an improved method, the ideal scenario is a change in sensitivity or specificity, which would therefore show an additional or higher level of impurities or degradants.

Another concern is assay bias. For the statistical analysis of data, it is important that both the new and old data are within specification. Based on the guidelines to industry, the cause of bias must be examined to see if such bias has an effect on the data. Hence, analyzing archived samples to show that impurities and degradants were always present is crucial.

For products that have already been marketed, there is a concern that new impurities may result in the requirement for new, additional, clinical work. If there are archived samples to show that the materials were always there, the clinical data will still prove that the drug is safe and efficacious, and that the newly measured impurities and degradants could not be measured with the previous method.

If such is the case, statistical analysis is still necessary to justify the bias; however, there is no need for additional clinical work. The new process is just implemented to compare and show an improved method. [11][12]

10.0 Conclusion
Preclinical drug discovery and development process, as well as manufacturing of biopharmaceutical products, involves a complicated process including rigorous (experimental) scientific study. By following regulatory guidelines, successful advancement of novel drug candidates requires early planning, setting aside archived samples, having a very tight validation report and study and, finally, having a well-planned, statistically rigorous comparability study.

If these steps are present, there is a high probability of a smooth regulatory process. Drug developers may expect to receive approval to use the new analytical method for a marketed product. And if the product is in a preapproval process, the expectation is that there is no need for additional questions from the agency. 

[a]UV-VIS spectroscopy (ultraviolet and visible spectroscopy) is typically used for the determination of protein concentration by either a dye-binding assay or by determining the absorption of a solution of a protein at one or more wavelengths in the near UV region (260-280 nm). Circular dichroism is another spectroscopic method used in the early-phase characterization of biopharmaceuticals (proteins).
[b]Surfactants are compounds that lower the surface or interfacial tension between two liquids.
[d] UHPLC and UPLC (Waters Corp.) allow for better separation of peptide mapping
[e]CBE-30 is similar to Changes Being Effected (CBE) and involves a filing with the FDA to gain approval of a moderate change (this may include a change that has a moderate potential to have an adverse effect on the identity, strength, quality, purity or potency of the drug product, as these factors may relate to the safety or effectiveness of the drug product. Based on the CBE-30, the FDA has 30 days to respond prior to implementation of any change. If a filer does not receive a reply from the FDA within 30 days, it is assumed that a change is approved.
[f]Chemistry, Manufacturing and Controls (CMC) is renamed to Pharmaceutical Quality/CMC

October 21, 2016 | Corresponding Author: Glenn Petrie | doi: 10.14229/jadc.2016.10.21.001

Received: August 19, 2016 | Published online October 21, 2016 | This article has been submitted for peer reviewed by an independent editorial review board.

Featured Image: Pharmaceutical scientific researchers analyzing liquid chromatography data; Pharmaceutical industry manufacturing laboratory Courtesy: © 2016 Fotolia. Used with Permission.

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Last Editorial Review: October 24, 2016

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Strategic Collaboration Between CMC Biologics and IDT Biologika to Manufacture Antibody Drug Conjugates

Denmark-based CMC Biologics, a company involved in the clinical and commercial manufacturing of monoclonal antibodies and other therapeutic proteins, and IDT Biologika, a privately-held life-science company, headquartered in Dessau, Germany with a 95 year history of expertise in research, development and manufacture of biologics for human and animal health, have formed a new, strategic, collaboration to provide a complete and efficient solution for the manufacture of antibody-drug conjugates (ADCs), a class of therapeutic drugs consisting of a cytotoxic drug linked to a monoclonal antibody that represents one of the fasting growing segments of the pharma and biotech industry.

Based on the agreement, CMC Biologics will perform process development and manufacture of the bulk monoclonal antibody and IDT Biologika will perform additional services from conjugation of the cytotoxic drug to the antibody substance through to the aseptic fill, finish and packaging of the ADC final drug product.

The joint manufacturing solution is expected to offer clients increased speed, reliability, quality manufacturing and a simplified supply chain, from DNA to finished drug product, for clinical trials and beyond through commercial manufacturing. Additional details about the collaboration between the two companies will be provided at the upcoming Drug, Chemical & Associated Technologies (DCAT) conference, March 14-17 in New York. Initial services will become available to clients in April 2016.

“The collaboration with CMC Biologics is an important step to provide full ADC manufacturing services to meet the needs of ADC development and production in this rapidly growing field,” noted Ralf Pfirmann, Chief Executive Officer of IDT Biologika.

“Our new collaboration permits IDT Biologika to leverage its biologics and cytotoxics capabilities and facilities, and their unique combination in the business, manufacturing and development portfolio at IDT´s Dessau headquarter site, to provide ADC developers with a highly reliable and efficient solution for early process development through clinical and commercial manufacturing based on our capabilities and experience. We see this as an important undertaking to make a meaningful difference in human health,” Pfirmann added.

“We are delighted to be working with IDT Biologika, one of the fastest growing and innovative CMOs in Germany and now in North America,” said Gustavo Mahler, PhD, Chief Executive Officer of CMC Biologics. “We share the common values with IDT Biologika with a constant focus on manufacturing excellence and a dedication to customer service.”

Manufacture of ADCs poses unique and highly complex challenges, requiring clean room biologic and high containment cytotoxic facilities, often involving multiple vendors and providers. CMC Biologics and IDT Biologika will be able to provide a unique complete manufacturing solution for ADC developers.

Last Editorial Review: February 18, 2016

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Report Presents Latest Development in CMO Market for ADCs

While the basic concept of Antibody-drug Conjugates (ADCs), a new class of biopharmaceutical drugs designed as a targeted therapy, is quite simple – a biological active cytotoxic or chemotherapy drug, is delivered to the target tissue through linking it with a monoclonal antibody – the practical challenge of manufacturing such complex and highly toxic molecules is huge.

In order to be successful in manufacturing the multi-component aspect of ADCs, it is necessary forContract Manufacturing Organizations or CMOs to understand the challenges involved and have both biologic and high-potency production facilities available.

The challenges for both biotech and CMO are widely differing and divers. As a new subindustry, ADCs, as a class, are growing in part as the technology within the subindustry grows, expands and become more refined. This growth requires significant ongoing – expensive – research and development. Furthermore, in a practical sense, most biotech companies, one of the major challenges in the manufacturing process of ADCs involves managing the supply chain and working with multiple CMOs.  This adds to the complexity of the manufacturing process, where, with the exception of just a few companies, one-stop-shops are rarity in this field.

Limited in-house manufacturing capabilities
Despite the fact that this new class of therapeutic agents is gaining increased attention from both small and large pharmaceutical companies, in-house manufacturing capabilities for these molecules are rare. Only a few ADC developers have in-house manufacturing facilities. The majority of the companies, including the leading technology providers, Seattle Genetics andImmunoGen, are dependent on contract manufacturers to supply the components.

Furthermore, most of the companies have a limited number of ADCs under development. Considering the utilisation rates are likely to be low in the near future, the investment required for setting up such high-containment biologic facilities offers a great financial risk. Hence, senior experts in the industry reveal that around 70%-80% of actual ADC manufacturing is outsourced.

A CMO market
Because of the complexity, majority of development and production work is currently being outsourced to specialist CMOs focused on one or more areas of ADC manufacturing. In examining the market, a surge in investments from the CMOs in expanding their facilities and capabilities in developing and manufacturing ADCs was seen. Such investment decisions have been driven by an increase in the demand for ADC production services from multiple drug developers.

The combination of challenges and market requirements results in a unique set of conditions driving the market today.

Market size
The global market for antibody drug conjugates was valued at $179 million in 2012 and is estimated at $396 million for 2013. However, analists projects the market to grow to nearly US $ 2.8 billion by 2018, and register a five-year compound annual growth rate of 48.1% from 2013 to 2018. This growth is also represented in the overall market for contract manufacturing of ADCs – which is likely to exceed US $ 1 to 2 billion in the coming decade.

Growing pipeline: beyond cancer
Although, there are only two marketed ADCs available today – ado-trastuzumab emtansine (Kadcyla®; Genentech) and brentuximab vedotin (Adcetris®; Seattle Genetics), a rich and growing pipeline is a very big opportunity for contract manufacturers. Furthermore, the presence of both large and small biotech companies is funding the expanding pipeline of ADCs, with more than 30 ADC-based drug candidates in clinical trials.

While most of this development is focusing on targeted therapies in oncology and hematology, it is likely that drugs will emerge that are not focused cancer but include other conditions as well. For example, Intellect Neurosciences is developing an ADC-type of drug candidate that involves conjugating an antibody whose target is amyloid protein to help arrest Alzheimer’s disease.

ADC Contract Manufacturing Market
The ‘ADC Contract Manufacturing Market, 2014-2024’ report provides an extensive study of the contract manufacturing opportunity for this emerging class of therapeutics. In writing the report, the authors have covered all aspects of this new class of drugs. They have also identified the CMOs active in this space, their capabilities with respect to ADCs, available capacity (clinical / commercial) for bio-conjugation and geographic location / spread of the facilities.

One of the conclusions of the report is that there are numerous partnership opportunities for CMOs to bring together their complementary skills. Such partnerships will enable further advancements in this field without significantly enhancing the capital exposure.


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