Focus on Standardization, Quality by Design, and Regulatory GMP

In this quarter's column, highlights from the IBC Single-use Applications meeting, the PDA Single-use Workshop, and the BioProcess systems Alliance International Single-Use Summit are presented.
Nov 01, 2011
Volume 24, Issue 11


Jerold Martin
At the IBC Single-Use Applications meeting, held in Boston on Jun. 6–9, 2011, I gave a talk entitled "Standardization of Single-Use...Pros, Cons and Possibilities." The topic of standardization has appeared in many surveys as one of the top 10 needs for expanding single-use implementation. However, there is little definition of what is meant by "standardization," which could be applied to many areas.

One particular area of discussion is the interchangeability of sterile connectors to enable single-use unit systems with sterile connectors from different suppliers to be linked. In preparing my talk, I also discovered that there is already an interchangeable "standard sterile connector" recognized by industry. If you search for this phrase in Google Images, you'll find a photo of a traditional two-way hosebarb fitting.

In my talk, I discussed how standardization of advanced sterile connectors must begin with the end-user's company. Different systems' assemblers and integrators can generally source whatever advanced sterile connector is specified, so the first effort must be for the end-user's company to decide what its preferred sterile connector will be. Since the introduction of the first advanced sterile connector (Pall's Kleenpak), there are now five additional designs on the market from other suppliers, but there is still no industry consensus on which design might become the "standard" of the future. Unlike the easily copied tri-clamp style hygienic flange connector, which is commonly used in stainless-steel and some single-use systems, or the aforementioned hosebarb fitting, many advanced single-use sterile connectors incorporate patented technology and designs. Users calling for the standardization of sterile connectors have yet to address which design should dominate or why the patent-holder should license their design to competitive suppliers. Once bioprocessers agree on a preferred design within their own facilities or companies, once there is consensus on an industry-preferred design (such as happened with tri-clamp style connectors), and once patents expire, options will appear to either "standardize" one of the original sterile connector designs. The alternative is that users will prefer an innovative proprietary design that is superior to current designs, but has yet to be seen. Until then, care has to be taken to avoid inhibiting innovation and it may not be realistic to expect meaningful voluntary standardization from the bioprocessing supply industry.

One area where there is an industry initiative underway to standardize connectors, however, is for polymeric tri-clamp style hygienic flange seal connectors. In response to stimulus letter from the Bio-Process Systems Alliance (BPSA), the American Society of Mechanical Engineers bioprocessing equipment standards group (ASME–BPE) has formed a task force to review the requirements for single-use polymeric tri-clamp style connectors and how the ASME–BPE Standard for stainless steel hygienic flange seal connectors can be modified in response to accomodate their use. Unlike their stainless steel counterparts, single-use polymeric tri-clamp connectors do not require cleanable finishes, crevice-free cleanable seals, or thermal resistance and mechanical strength suitable for steaming in place. They also do not require tolerances that are readily achieved with stainless steel on a lathe, but are difficult to achieve with plastic molding, thus incurring unnecessary mold costs. Expansion and relaxation of the ASME–BPE standard to cover the specific requirements for single-use polymeric tri-clamp style connectors will be a benefit to both suppliers and users.

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