Published Nov 29, 2017 |
213 Pages |
Pub ID: KLI15540315
Biopharmaceutical Contract Manufacturing (BCMO) Market - by Type of Service, by Organization and by Region
How Large is the Biopharmaceutical Contract Manufacturing Opportunity? Will the Drive for New Biopharma Last? Who are the Key Players in this Industry?
These are among the questions answered by Kalorama Information's report on biomanufacturing organizations, labelled BCMOs. The market for biopharmaceutical manufacturing is driven by many factors - an aging population, demand for more effective solutions to disease, and the expiration of blockbusters. Over the past several years, an unprecedented number of blockbuster drugs have lost patent protection, and this trend is expected to continue through the foreseeable future. Because generic medicines are priced at a discount of up to 90% of the cost of the original drug, yet are considered therapeutically identical, their growing usage represents a particularly threat to blockbuster drugs. Yet pharmaceutical companies cannot always produce their needed pipeline in-house. This has created an ideal market environment for biopharmaceutical contracting.
Biopharmaceutical Contract Manufacturing (BCMO) Market - by Type of Service, by Organization and by Region contains the following market information:
- BCMO Market 2012-2022
- Top Company Revenues
- BCMO Country Markets (U.S., Western Europe, Eastern Europe, China, India, Other Asia, Latin America, Rest of World)
- BCMO Market by Segment (Clinical Manufacturing, Commercial Manufacturing)
- Company Profiles
- Preferred Vendor Relationships, CMO M&A, Big Pharma in CM, Vertical Integration and Other Important Trends
This report includes extensive coverage of the biotechnology segment of the global drug development and manufacturing industry. Sales estimates for each market segment represent global revenues and are expressed in current dollars. Estimates are provided for the historic 2012 to 2017 period and forecasts are provided through 2022. Historical information for this report was gathered from a wide variety of published sources including company reports, filings, websites and presentations; government documents; legal filings; trade journals; newspapers and business press; analysts’ reports and other sources. Interviews with company representatives were conducted to capture the perspectives from industry participants’ point of view and assess trends, and form the basis of the forecasting and competitive analysis.
Best efforts were made to determine BCMO fees by region in the many instances where these are not specifically reported by each company. Contract manufacturing fees were allocated to the country/region of production, not to the region of export; therefore, companies with production facilities in a single country, such as China, were deemed to be regional Chinese players even if they have extensive export operations to many other countries. These determinations were made on the basis of currently available information. Where reliable information was not attainable, no estimate was attempted.
Section on The Rise of CDMOs
Increasingly, CROs have been adding BCMO capabilities to create full service CDMOs. In this report, all BCMO estimates in this report pertain primarily to contract manufacturing and do not include contract research services. In some discussions of BCMO forecasts, CRO estimates are included to provide context and comparison; however, these are separate from BCMO revenues.
While some regions, such as India, have developed local acronyms for contract work (ie. CRAMS to represent custom research and manufacturing services), this report will utilize consistent, globally-accepted acronyms throughout all regions. This includes CRO (contract research organization), BCMO (biopharmaceutical contract manufacturing organization) and CDMO (contract research and development organization).
It should also be noted that many other sources attempt to quantify the contract manufacturing industry and may use different methodologies that include, for example, contract research and development fees. Due to the bottom-up methodology utilized in this report, estimates may conflict with those in other market research reports. While an attempt was made to reconcile this data with other analysts, where opinions differed, information obtained directly from each manufacturer, via primary or secondary sources, was given precedence.
Excluded from this report are fees related to contract manufacturing of:
- Non-prescription (OTC) medications;
- nutritional and herbal supplements;
- cosmetic and personal care preparations;
- agricultural and other chemicals.
Companies Covered in This Report Include:
Asahi Glass Co.
Avara Pharmaceutical Services
Baxter Biopharma Solutions
Boehringer Ingelheim Bioxcellence
Dr. Reddy’s Laboratories
Fresenius Kabi Product Partnering
Fujifilm Diosynth Biotechnologies
Jubilant Life Sciences
Juniper Pharmaceutical Services
Patheon/Thermo Fisher Scientific
Rentschler Biotechnologie Gmbh
Rovi Contract Manufacturing
Sl Pharma Labs
Strides Shashun Ltd.
Symbiosis Pharmaceutical Services
Vetter Pharma International Gmbh
Strengths of the BCMO Model
Simply put, BCMOs focus on manufacturing. This allows drug developers to focus on their own core competencies, which often does not include manufacturing. In Contract Pharma’s 2017 survey of outsourcing practices, for example, 33% of respondents indicated that they outsourced to focus on their core competencies. A variety of factors are fuelling strong and continued increases in BCMO usage. These include:
shifting manufacturing requirements;
lead time savings;
access to expertise;
established producction of APIs.
Cost savings are also important. Drug developers, most of which are publicly traded, are experiencing strong pressure from shareholders to control expenses. Although all aspects of drug developers’ operations are subject to potential cost cutting as a means to remain competitive, manufacturing plants are a particular area for scrutiny due to the high capital investment in personnel, equipment and facilities that they require.
Manufacturing accounts for up to 16% of the total cost of sales of the average drug company, including the cost of raw materials, workforce, facilities, etc. Workforce costs can be particularly significant, including not only salary expenses but also costs associated with identifying, recruiting, hiring, relocating and providing benefits for internal employees. In addition to this portion of cost of sales, most of the 7% of total expenditure that is allocated to capital investment is spent on new plant and equipment to be used in drug production. Therefore, manufacturing absorbs as much as 23% of the total revenue generated by sales in a typical pharmaceutical company, according to PhRMA. This has grown from about 15% since the mid-1980s.
Outsourcing serves as a means of converting these high fixed costs into variable costs, so that drug makers only pay when they are actually producing product. In other words, they do not incur expenses when facilities sit idle. This is important, since it is not uncommon for factories that were specifically developed to produce a certain type of drug to go unused when demand for that product fails to meet expectations. Furthermore, contracting out production of a product liberates capital and resources which the pharmaceutical company can use in areas where they can add greater value, such as research and development or sales and marketing.
Specifically: Contract manufacturers can spread overhead over a number of products within the facility to reduce per product costs; additional costs for in-house manufacturing, such as validation, regulatory audits, etc. are avoided; new chemical entities are increasingly complex and require novel bulk synthesis techniques, which are often performed more cheaply by companies with specific expertise; contracting allows companies that require a range of different manufacturing processes to run a number of different processes at reduced cost. These cost savings can be significant in light of the financial risk associated with poor planning. Biologics facilities are even more expensive, with a 30,000 to 40,000 liter plant costing $400 million to $500 million in fixed costs and another $100 million to $150 million in annual operating expenses./div>
Contract manufacturing particularly makes sense for biotech products because BCMO margin requirements are quite different from those of biotech companies. Contract manufacturing does not yield the same type of returns, making it difficult for biopharma companies to justify engaging in contract manufacturing. Working with a contract manufacturer can therefore provide biotech companies with the flexibility to focus their efforts and investment on the parts of the biotech value chain with the potential to generate greater value to them.
Risk Reduction Strategies Play Into BCMO Business Model
Risk reduction is also a major strength of BCMO usage. In today’s pharmaceutical marketplace, long term production planning is becoming increasingly difficult as demand for products fluctuates. This is a direct result of a high number of patent expirations coupled with rising uncertainty about the future of new products, as some new products fail to perform despite their manufacturers’ high expectations. This has occurred with many different classes of pharmaceutical and biotech products, and has resulted in drug makers’ reluctance to invest large amounts of capital in allocating manufacturing space, especially to new and unproven products that in new market segments.
Occasionally, however, drug makers run the opposite risk, namely that demand will far exceed production capability. This occurred with Immunex’s Inbrel, and alerted the industry to the impending shortfall in biomanufacturing capacity. Enbrel was first approved for the treatment of rheumatoid arthritis at the end of 1998. After 2 years on the market, the drug was so popular, that Immunex was unable to manufacture enough product to meet demand and had to introduce a waiting list for prospective patients. Contract manufacturing, where the BCMO has the flexibility to scale up production, can also address this production risk.
As product lines shift, so do their manufacturers’ production requirements. For example, in the 1980s and 1990s, most medications were formulated in a solid dosage (tablet or capsule) that was taken two or three times per day. This required very large production volumes and big pharma therefore scaled up their solid dosing manufacturing lines at significant expense. New technologies, however, have enabled the development of other formulations (inhaled, transdermal, liquid, etc.) as well as controlled release and extended release solid doses that need be taken just once daily. Batch sizes are considerably smaller, and based on flexible processes. This has significantly reduced the need for high volume solid dosage production among big pharma, but at the same time, it has increased this need among the smaller pharmaceutical companies that are acquiring mature, multiple dosage solid products from these companies and the generics manufacturers that are launching generic equivalents. As the products offered by these latter two groups of players will eventually also be replaced by reduced dosage equivalents, these companies are either reluctant or unable to invest large sums in solid dosage production and therefore turn to BCMOs to meet this need.
In terms of lead time, utilization of a BCMO can often allow sponsors to save considerable time in establishing manufacturing processes. Leveraging the resources and expertise of third party manufacturers can eliminate delays associated with oversights and mistakes made by individuals with inadequate experience in performing product and process development for a material produced under Good Manufacturing Practice (GMP) standards. Since these manufacturing processes are often established during clinical testing to produce material for human trials, production time savings are important as they can reduce overall trial times and allow a drug developer to get a product to market more quickly.
Production of certain specialized products may also be established more quickly with a BCMO than with in-house resources. For example, more potent, low-dose products often have to be specially prepared in dedicated manufacturing facilities. Because of the danger of cross-contamination between facilities, dedicated production plant or time-consuming sterilization and decontamination procedures between production runs of different products are necessary to the production process. Outsourcing production to an external manufacturer can help reduce this lead time as the contractor may have access to suitable facilities and can quickly adapt them to the sponsor’s product.
However, sponsors must often devote significant time to establishing and managing relationships with BCMOs. Because the market for third party manufacturing is still very fragmented, relatively few companies are capable of taking over a large portion of the manufacturing process, so complex deal structures are typically required that involve several different players. Because of this, the coordination of the numerous processes and parties involved requires significant time and expertise on the part of sponsoring companies. Therefore, while the greatest value from manufacturing outsourcing typically comes from when the external manufacturer is utilized during the early stages of a product’s development, this benefit may quickly erode as the product is commercialized if the sponsor is not able to structure and maintain appropriate relationships.
Multiple Benefits to The Use of BCMOs
Furthermore, drug developers with more limited resources gain access to specialized expertise by using BCMOs. For example, processes such as manufacturing validation, process development and regulatory compliance often require considerable expertise and start-up companies are unlikely to be familiar with these areas. Some BCMOs focus on niche areas - Baxter BioPharma Solutions contract manufactures premixed parenteral drugs in flexible plastic containers and has become a specialist in frozen premixed drug products; this is a process that requires sophisticated controls on temperature, processing times, component addition sequences and additional rates which most sponsors do not possess in-house. BCMOs can therefore fill critical gaps in sponsors’ capabilities; their personnel can also provide sponsors with learning opportunities that help build internal expertise.
This can be particularly beneficial from a regulatory perspective. As manufacturing specialists, BCMOs diligently work to meet regulatory requirements and ensure product compliance. This is important, since regulators tend to frown upon “testing in quality”, or establishing quality in terms of the final product only; rather, the manufacturer must demonstrate that all of the materials and media sued in the production process were free of contaminants and that no infectious agents were introduced into the product during manufacture. BCMOs also tend to keep abreast of newer regulatory initiatives, such as Process Analytical Technology (PAT). This requires in-process testing conducted while a product is being produced. Although many believe that PAT will ultimately reduce cycle times and improve product performance and compliance, it nonetheless represents an extremely high capital investment to install in-process equipment sensors, systems and automated analytical equipment that is prohibitively large for smaller manufacturers.
European Markets for BCMOs
In Europe, the European Clinical Trials Directive has had a significant impact on the biomanufacturing sector, requiring extensive biocomparability studies if a protein manufacturing process is changed mid-way through clinical development; because of this, companies are investing in process development capabilities at an earlier stage than ever before, paying close attention to the design of cost-efficient processes right from early clinical stage development. Thus, the focus of contract manufacturers is to develop cost-efficient and robust technologies that allow them to increase their yields and reduce their production cost.
These and other strengths have resulted in BCMOs now being well established in the production of active pharmaceutical ingredients (APIs). In Contract Pharma’s 2017 survey of outsourcing practices, for example, almost half of respondents indicated that they currently outsource production of APIs.