CDMO | Contract Development & Manufacturing

Overview of custom synthesis & drug product manufacturing services offered by contract development & manufacturing organizations (CDMOs) for API & FDF

Q1. What is a CDMO?

A pharmaceutical contract development and manufacturing organization or a CDMO, is a company which specializes in providing CDMO services ranging from drug product development & manufacturing to pharmaceutical packaging services including pharmaceutical serialization and aggregation, with complete trust and transparency. An increasing complexity in the development of new molecular entities (NMEs) has created a need for niche capabilities and competencies that pharmaceutical companies prefer to access externally via a CDMO facility rather than incorporate in-house.

Contract development and manufacturing organizations (CDMO's) activities refer to the production of goods by a production plant, but under the label or brand of another firm. Contract manufacturers provide such support services to several firms based on their own or their consumers' designs, formulas, and specifications. In many cases they provide a combination of scientific expertise and integrated project management combined with cost-effective CDMO services, which in turn help their partner companies get drug products to market more safely and rapidly.

Q2. What is drug product manufacturing?

Drug product manufacturing is the process by which pharma companies produce drugs at an industrial scale. The full development program can often be broken down into a series of unit operations which run from pre-formulation development, to clinical trial manufacturing and commercial manufacturing. In today's day and age, pharma companies often need to access specialized manufacturing resources, facilities, and capabilities to advance a drug from the development phase through to commercial production. Therefore, there is an increasing trend of outsourcing drug formulation, development and delivery services to contract development and manufacturing organizations - CDMOs (or contract manufacturing organizations - CMOs).

Q3. How has the role of pharmaceutical CDMOs evolved over time?

Outsourcing manufacturing of drug products has evolved from being a transactional need to a strategic function. Working with a limited number of supplier partners helps sponsor companies to optimise costs, speed products to market, reduce internal complexity and increase agility, while ensuring that these partners focus on investing capital to meet their future needs. While CDMOs have been a feature of the pharmaceutical industry for some time now, they emerged as critical components for commercial manufacturing in the past 20 years.

During their formative years, CDMOs were involved in the production of small API needs, cGMP intermediates, and providing other specialized services. However, 1996-2007 saw multiple strategic acquisitions by companies looking to become a fully integrated CDMO or a one stop shop CDMO, such as the ones made by Lonza and Cardinal Health. The CDMO market is currently undergoing consolidation through M&As on the back of sustained customer demand for CDMO services and as market participants continue to acquire the necessary scale and capabilities to become more relevant to their most important biopharma customer partners.

The three factors that contributed to the industry’s launch from 1996-2007 are:

1. Pharmaceutical companies ridding themselves of aged-off patent assets for nominal prices, being acquired by emerging pharmaceutical CDMOs.

2. Certain companies such as Vertex, Gilead, and Shire, which surfaced during the early stage of the pharma CDMO companies’ explosion, remaining devoted to outsourcing some or all of their development & manufacturing requirements.

3. The success of clinical research organizations (CROs) in developing positive relationships between pharma companies and contract service providers, on the foundation of which CDMOs then built strong lasting relationships.

Q4. What are the services offered by CDMOs?

Contract Services offered by fully integrated CDMOs (contract development and manufacturing organizations) include, but are not limited to, pre-formulation, formulation development, stability studies, method development, pre-clinical and Phase I clinical study materials, late-stage clinical trial materials, formal stability, scale-up, registration batches and commercial manufacturing. CDMOs often offer operational excellence in CDMO services such as early formulation development services, analytical development services, pharmaceutical packaging services and have bulk manufacturing capabilities as well.

Q5. What are the advantages & disadvantages of a CDMO?

Advantages:

1. Cost Saving and Restructuring: Outsourcing manufacturing to an end-to-end CDMO or full services pharmaceutical CDMO, turns fixed production costs into variable costs, giving consumers the flexibility of choosing a low-cost CDMO service provider. Therefore, many pharmaceutical companies outsource their manufacturing processes to low cost economies like India and China.

2. Reduced Operational Cost & Minimized Ownership Cost: Outsourcing production reduces excess production capacity by divesting facilities and minimizes investments in capital intensive facilities. The outsourcing firm can make strategies to lower company expenses ready by reducing these fixed costs and modifying their capacities.

3. Focus on Core Strengths: The hiring firm doesn’t need to purchase manufacturing facilities, pharmaceutical manufacturing equipments, machinery, raw materials or hire labor to process the goods. Instead, they are able to solely focus on placing orders with contract development and manufacturing organizations (CDMO), advertising, and marketing the product.

4. Accelerated time to Market: Outsourcing reduces the total time allotted for a drug product’s project management. This in turn shortens the time to market the product, which translates to quicker income and a longer duration of its patented life enabling the company to introduce new products into the market and ultimately accelerating time to market.

5. Regulatory Support: Contract manufacturers have a good understanding of their industry and FDA – health authorities’ activity, which they develop through years of experience. They can handle a project from start to finish, identify flaws and spot potential risks to quality agreements via regulatory intelligence monitoring throughout the supply chain and they thereby offer regulatory services.

6. Flexibility: Technologies: Outsourcing gives companies access to cutting edge technologies on a need basis, thereby giving hiring companies organization flexibility. This is important as owning novel technology can be very costly.

Disadvantages:

1. Quality Management System: In outsourcing, customers give up all decision making to the contracted company. If the wrong innovative CDMO solution provider is chosen who doesn’t match their partners’ needs, it could lead to a bad customer experience. Furthermore, differences in standards of customer services could lead to quality problems.

2. Less Control over Production: In-house productions provide the company ultimate control over the quality and the quantity of the products. Also, the company can easily change scope, adjust timelines and increase or decrease volume based on the market demand. Outsourcing production hands this power over to the CDMO quality charter and CDMO quality assurance facilities.

3. Loss of Intellectual Property: If a drug company has a proprietary right to a product which is responsible for most of their annual income, then it is recommended to keep the manufacturing process in-house as any margin for error could severely affect the brand name. On the contrary, for an established drug it makes more sense to outsource them. This is also in order to safeguard oneself against the risk of losing intellectual property to those working in production facilities.

Q6. What are the trends/outlooks of the pharmaceutical CDMO industry?

Over the past decade, the pharmaceutical industry has witnessed rapid growth in outsourcing services, driven by various factors including the growth of small molecules, increasing API complexities and the need to optimize costs. 2019 proved to be a stellar year for the biopharma industry in general and for contract manufacturing organizations (CMOs) in particular. Many pharmaceutical CDMOs experienced double-digit growth, and the key indicators of opportunity for CDMOs, although down from the blowout levels of 2018, performed well.

The global pharmaceutical contract development and manufacturing market is projected to reach $126.6 billion by 2024 from $90.0 billion in 2019, at a compound annual growth rate over 6%. A main driver behind this growth is investment in advanced manufacturing technologies by contract development and manufacturing organizations (CDMOs). Additionally, mergers and acquisitions continue to be a big part of the CDMO story. There were three blockbuster deals completed in 2019, and more big deals are likely in 2020.

Thermo Fisher Scientific acquired Brammer Bio for $1.7 billion, Catalent acquired Paragon Bioservices for $1.2 billion, and Permira acquired Cambrex for $2.4 billion. These current trends exemplify that big pharmaceutical companies are embracing outsourcing to a CDMO facility as a strategic move to accelerate their drug development timelines. Furthermore, analysts report that pharma CDMOs with capabilities in gene and cell therapy, mammalian cell culture, HPAPIs (more potent APIs), and injectables, along with the vital analytical development services and regulatory support, should do very well.

However, not all CDMOs will have the same fate because they lack the portfolio of capabilities the contract development and manufacturing organization offers the market. This includes many pharma CDMOs in Europe that are stuck with undifferentiated low-value capabilities for which there is an over-abundant supply in the market.

Q7. What are the limitations and challenges faced by CDMOs?

While the end-to-end CDMO model as a whole is thriving, many CDMOs are facing challenges due to fierce competition, cost pressure, constant technological innovations and consolidation. These challenges are outlined in more detail:

• Protectionism: One of the biggest limitations to pharmaceutical CDMOs in the foreseeable future is the global push towards bringing manufacturingback into native countries. A shift towards in-house and local manufacturing is expected as a response to this outcome.

• Resources: A range of specialized technologies, processing and infrastructure is needed to support drug programs from concept to full commercialmanufacturing.

• Continuous Improvement Process: CDMOs increasingly need to demonstrate a strong track record of implementing quality by design (QbD), PAT, and continuous improvement. Meeting the continuous processing challenge is becoming ever more critical due to the need to significantly shorten drug development time, optimize cost efficiency, reduce wastage during production, and to find ways to execute drug development with smaller quantities of available high-value API’s.

• Adaptability & Time Constraints: A challenge that CDMOs are facing is the flexibility to adapt to each project dealing with different customers and the timelines for pharma CDMOs to deliver end results are often aggressive or unrealistic.

• Consolidation: One of the perennial issues facing the CMO/CDMO sector is consolidation, under the principle that there’s too much capacity overall and that a winnowing out through mergers and shutdowns will lead to more efficient and effective outsourcing.

• Data Integrity: A CDMO partner often faces the suspicion of the hiring firm when it comes to full traceability and deviation management.

Q8. What are the criteria for selecting a CDMO partner?

A logical first step in selecting a CMO (contract manufacturing organization) or a CDMO (contract development and manufacturing organization) involves making an assessment of internal capabilities, strengths, and needs that can then be overlaid on anticipated external requirements. Following which, the criterions for selecting a compatible pharmaceutical CDMO partner are divided into two broad categories, namely culture and quality. Fully integrated CDMOs that are likely to make agile CDMO partners are flexible, good at problem solving, and have widespread experience of different dosage forms and production scale-up.

The following three factor checklist can used to select the right CDMO partner for you:

1. Capabilities, capacities, and technologies - match your current and future needs.

2. Regulatory - compliance. Track records of contract services and quality agreements can be used when assessing a company's regulatory standings.

3. Partnership: Look for a partner, not just a provider.