Fill and finish operations over the past 25+ years have remained relatively stable in terms of technology, capacity, and competitive environment. However, over the past few years, this important area has rapidly gained importance as biologics have taken on greater value, and regulators have applied more scrutiny to the quality and safety of these high value, late-stage operations. Through our industry research, BioPlan has quantified several key trends associated with fill and finish operations that are worth keeping an eye on this year.
Trend No. 1: Adoption of Single-Use Devices
The trend towards greater penetration of single-use devices throughout biopharmaceutical manufacturing operations is taking hold in fill-finish, too. In fact, our 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production [1], which contains a new chapter on fill and finish operations, reveals that single-use and disposable equipment adoption is the most important trend in fill and finish today, cited by a majority of experts we surveyed. Additionally, single-use devices tied for the lead when we asked respondents which fill and finish technologies they plan to implement during the next 24 months at their facilities.
The use of disposable equipment dovetails with another trend: facilities becoming more multi-product-use oriented. Facilities are seeking to decrease the cost of goods by increasing facility utilization, with multi-product strategies based on the deployment of single-use equipment.
We interviewed experts in fill and finish to further investigate this trend. These experts see benefits to single-use adoption even while recognizing potential drawbacks.
- Peter Pekos, CEO and President of Dalton Pharma Services, a fill/finish CMO: “Use of single use systems completely eliminates the issue of cross contamination arising from equipment. It can speed up getting the customer’s product into production with a lower up-front cost as you don’t have to buy expensive steel tanks etc. with long lead times. There are still trade-offs with either approaches but single use is becoming a more attractive option.”
- Martina Ferneman, Corporate Development Manager, Recipharm: “Since no cleaning procedure has to be established and aseptic connections are easier to be built-up the use of single-use equipment is not only faster, but also safer than conventional equipment with regards to contaminations and aseptic handling. However…there is a risk of potential interactions between the product contact material and the bulk drug substance. Therefore, an evaluation of leachables and extractables has to be performed.”
- Jim Agalloco, President, Agalloco & Associates: “I anticipate increased adoption of single use disposable filling systems in virtually all aseptic filling operations. The risks associated with set-up of filling systems as well as the complexities of their sterilization suggest adoption of singe use systems as a replacement from filter through filling can be expected. Improvements in technology combinations will further improve aseptic systems.”
Trend No. 2: CMOs to Adopt New Technologies, Grow
Fill-finish activities are one of the most outsourced activities today, according to our annual study. This year, more than 7 in 10 qualified respondents reported that they are outsourcing at least some of their fill and finish operations. Unlike some activities even more commonly outsourced (such as analytical testing of bioassays), those who outsource fill and finish operations tend to do so at quite a high level. In fact, among those outsourcing this activity, almost half said they outsource almost all (80-100%) of these operations.
In sum, we see from our study that more than one-third (35%) of biopharma industry fill and finish operations are outsourced, a greater level than for any other activity we identified. We also note that 1 in 5 respondents expect to outsource fill and finish operations at significantly higher levels over the next 24 months, although this figure is lower than in recent years.
Figure 1. Most Important Trends in Fill-Finish, Select Results Source: 12th Annual Report and Survey of Biopharmaceutical Manufacturing, April 2015, www.bioplanassociates.com/12thThat may be due to unused in-house capacity. In a recent white paper2, we interviewed several industry experts, finding that in-house capacity utilization was not currently constricted for any common fill-finish operation, including vialing, prefilled syringes, or lyophilization. For CMOs to draw client interest, adopting new technologies will prove to be a competitive advantage. CMOs involved in fill and finish operations commented as follows:
- Martina Ferneman, Corporate Development Manager, Recipharm: “Innovation in fill-finish will probably have the effect to increase the focus of MAH to strategic products and to outsource bigger shares of products. This could be beneficial for CMOs able to invest to fit the new rules.”
- Peter Pekos, CEO and President of Dalton Pharma Services: “CMOs who implement flexible and innovative technologies to make manufacturing or development more efficient, faster, compliant or more economical all serve to make them more attractive to customers. If a CMO offers a specialized service they can apply it to many different projects and customers it will likely be more financially sound for a company to outsource to a qualified CMO.”
Another trend likely to be found in the outsourcing business is the growth of fill and finish CMOs through investments and mergers and acquisitions. Amid some high-profile exits, we have also noted a number of such investments and acquisitions within the past 18 months, whether they be Pfizer’s acquisitions of Hospira and InnoPharma, Vetter’s investments in upgrading its US and German facilities, or Baxter’s investments in its German facilities. Recently, a privacy equity firm – Water Street Healthcare Partners – announced that it had bought generic injectables CMO Custopharm, sensing an opportunity due to an increasing number of generic injectable products coming to the market. Until recently, CMOs offering full scale manufacturing has been limited, especially for formulating and filling certain viral sterile products, and for new clinical studies.
Trend No. 3: The Increasing Use of Automation in Full Isolator Units
As with adoption of single-use devices, automation is a key trend identified in our latest annual report. In fact, fill and finish experts responding to our survey were as likely to say they would be adopting automation technologies at their facilities over the next two years as single-use fill-finish devices. The use of automation in full isolator units to reduce the need for operators also emerges as a top trend. The elimination of human intervention – and associated reduction in staffing needs and operator risks – is the basis upon which isolators are being embraced.
Industry experts had this to say about automation over the next five years:
- Ronald Malone PharmD. Sr., Principal Scientist, Novartis Vaccines: “I envision continued regulatory pressure to eliminate humans from direct contact with products being formulated and filled aseptically.”
- Jim Agalloco, President, Agalloco & Associates: “Improvements in technology combinations will further improve aseptic systems. Isolators, automation, robotics, machine vision, serialization and others will combine to provide fill/finish systems that far exceed the capabilities of those that rely on personnel proficiency. These systems will not only perform better, they will reduce operational costs in the same way that technological advances have improved automobiles and consumer electronics.”
- Scott Ferguson, Business Development Manager, Groninger: “More focus on completely automated lines, i.e. completely removing the operator from the process; no glove ports or defined interventions at all.”
- Peter Pekos, CEO and President of Dalton Pharma Services: “Isolator technologies in sterile fill-finish operations, not only reduce labor…the greatest risk to sterility is posed by human intervention. Isolators take much of the risk away by eliminating most human interaction. Isolators do appear to be a large factor in the future of sterile manufacturing because they help manufacturers to be more compliant in the long term and reduce their manufacturing risks…the reduced risks may offset [any] additional costs.”
Conclusions
These three trends – adoption of single-use, automation technologies, and new investments in fill and finish outsourcing – are among the most important to this industry segment today. But many other trends are also emerging and will play an important role in future analysis and development for this segment. These include:
- The emergence of fill and finish facilities in developing regions;
- Use of complex administration systems such as novel prefilled devices; and
- Increased serialization and product labeling to improve anti-counterfeiting.
In terms of adoption of new and better fill-finish technologies, only 18% of this industry segment has indicated it has not been considering adoption of new technologies during the next 24 months. Of the great majority expressing interest, the current hot areas include:
- Single-use Fill-Finish devices
36.4% (of industry segment respondents indicating) - Automation
36.4% - RABs Line (New Facility)
27.3% - Isolator Line (Existing facility)
18.2%
Other areas of new technology interest include: RABs Line (Existing facility), closed vial filling, advanced aseptic processing with blow fill seals.
With the current industry focus on quality and multi-product strategies, it will be interesting to see how these trends take root this year and in those to come.
References:
- 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, April 2015, Rockville, MD www.bioplanassociates.com/12th
- BioPlan Associates, Trends in Aseptic Bioprocessing Capacity for the Fill and Finish of Recombinant Biologics: An Analysis of US and European In-house Capacity and Capacity Utilization (BioPlan Associates, December 2014).
Eric S. Langer is president and managing partner at BioPlan Associates, Inc., a biotechnology and life sciences marketing research and publishing firm established in Rockville, MD in 1989. He is editor of numerous studies, including “Biopharmaceutical Technology in China,” “Advances in Large-scale Biopharmaceutical Manufacturing”, and many other industry reports. [email protected] 301-921-5979.www.bioplanassociates.com
Survey Methodology: The 2015 Twelfth Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production yields a composite view and trend analysis from 237 responsible individuals at biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) in 28 countries. The methodology also included over 164 direct suppliers of materials, services and equipment to this industry. This year’s study covers such issues as: new product needs, facility budget changes, current capacity, future capacity constraints, expansions, use of disposables, trends and budgets in disposables, trends in downstream purification, quality management and control, hiring issues, and employment. The quantitative trend analysis provides details and comparisons of production by biotherapeutic developers and CMOs. It also evaluates trends over time, and assesses differences in the world’s major markets in the U.S. and Europe.