By Eric Langer, President and Managing Partner, BioPlan Associates, Inc.
Even the way devices are connected raises debate
The spread of single-use devices in the biopharmaceutical manufacturing industry has been well-documented, with some devices reaching penetration rates approaching 90 percent, according to various studies conducted by BioPlan Associates. Yet there remains plenty of room for further adoption of single-use, disposable devices, particularly in commercial scale production, where they have yet to displace traditional stainless-steel systems.
But the debates over standardization continue. And even the most basic connectors create controversy. The ability to hook up and integrate various devices is an increasingly important factor as single-use applications push into mainstream biopharmaceutical manufacturing. Connectors can allow for interconnectability between various single-use components and vendor devices, allowing end users a plug and play approach that permits a greater assortment of options. From this perspective, connectors play a significant role in the expanding use of single-use equipment.
This industry segment is still in its early stages, and it is currently faced with an assortment of vendor devices, many of which present difficulties with interoperability. If connectors are to expand single-use penetration, suppliers and end users will likely need to agree on aspects of physical standardization — similar to how computer connectivity moved from various sizes and configurations to more common USB-type connectors. In fact, connector compatibility is one of the most sought after areas for standardization in the single-use arena.
In BioPlan Associates’ latest annual industry study, the 11th Annual Report and Survey of Biopharmaceutical Manufacturers (see www.bioplanassociates.com/11th), respondents were asked which of several areas they felt were important for single-use/disposable vendors to work harder to standardize. Connector compatibility (interchangeability) was near the top of the list with 88 percent of global respondents considering standardization “important” or “very important.”
A BASIC CHOICE: GENDER OR GENDERLESS CONNECTORS?
The inherent issue with standardization is that some vendors will have to change their existing product lines to meet whatever standards are set. For connectors, the most basic standardization boils down to a binary choice: gender or genderless connectors.
Genderless sterile connectors are those where both connector ends are the same (hence genderless). These tend to be uncomplicated and require fewer parts for inventory. Gendered sterile connectors, with their different ends, are slightly less straightforward to use and require more inventory, but generally are perceived to present a lower risk of incorrect connection.
Competitive aseptic options on the market include GE’s ReadyMate (genderless) and Pall’s KleenPak (gendered). Each can be gamma sterilized or autoclaved and come in a variety of sizes. Pall was one of the earliest entrants into the field and provided a huge boost when it shortened the connection time by introducing its half-inch connector.
INDUSTRY ATTITUDES ABOUT GENDER
To gauge industry attitudes to gendered and genderless connectors, BioPlan Associates carried out a small survey of qualified individuals with interesting results. Some 73 percent of the 26 respondents surveyed said they prefer genderless sterile connectors for their clinical-scale and larger bioprocessing, as opposed to the remaining 27 percent who favor gendered sterile connectors.
We explored the reasons why respondents made those choices. Sorting respondent comments into broad categories, the survey yielded some intriguing results: While the simplicity and inventory control afforded by genderless connectors are key considerations, risk mitigation is top of mind with the majority of those who selected risk mitigation as a reason for their preference for gendered rather than genderless connectors. This suggests some ambiguity: While the industry wants genderless connectors, its most common reason for selecting a connector focuses around risk mitigation (over a third lean toward risk factors, vs ~71 percent focusing on reasons related to genderless connectivity).
Representative comments offered along with the survey responses are similarly illuminative:
In favor of gendered connectors:
- “Risk mitigation with regard to incorrect connections — possibility to establish workflows based on ‘one-way-correct’ connection [connectivity defines the process].”
- “Gender-sterile connectors [ends are different] are more reliable in my opinion.”
- “Lower risk of incorrect use.”
- “The biggest contributor to [problems] in single-use production is the operator. This is a small and easy way to minimize errors.”
In favor of genderless connectors:
- “Genderless help with inventory control and simplify preparation.”
- “Allows the flexibility to choose which attachment to make at any given point in the process.”
- “You always want it to be as simple as possible.”
- “Having genderless connectors allows for more flexibility when having to come up with disposable strategies.”
- “Easier to set up bags and tubing with connectors that can connect to each other for multiple combinations.”
VENDORS SHOULDN’T REST EASY
While study participants seem to prefer genderless sterile connectors, questions of reliability are paramount, and as one respondent noted, there are other questions surrounding cost and availability to consider. That suggests the choice may not be as clear-cut as it initially might appear.
One thing seems clear from BioPlan surveys: The industry is looking for innovation in this area. According to our latest industrywide study, some 38 percent of respondents consider disposable bags and connectors to be among the top five areas they want their suppliers to focus their development efforts on. That was the fourth-highest result of the 21 innovation areas listed in the study. These devices have consistently seen hot demand for innovation over the past eight years.
Suppliers responding to the study were a little less committed to innovation in this area, though. Asked which new technologies or new product development areas they are working on today, roughly one-quarter (27.3 percent) cited disposable connection technology. As vendors look to increase their market penetration, standardization of their products — including of connectors — may be unavoidable. Currently, while three-quarters of the industry believes it important or very important that single-use vendors standardize their devices, only 28 percent are satisfied to any degree with their current vendors in terms of device standardization.
As one director of technology for a large biopharma noted, “Suppliers will only truly achieve the SUS (single-use system) value proposition they champion if they resolve these variability concerns.” For manufacturers of single-use connectors, end user desire for standardization is particularly acute. Some financial pain may be inevitable in the short term, but suppliers may well win in the long term by standardizing their offerings to meet end user demand. An interesting bellwether for the industry’s commitment to standardization may be in the most basic of choices: gendered — or genderless.
Survey Methodology: The 2014 Eleventh Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production yields a composite view and trend analysis from 238 responsible individuals at biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) in 31 countries. The methodology also included over 173 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.