Trends Toward Standardization
Although some aspects of single-use components can be standardized, it is unlikely that any materials or design features will become a commodity
This is the first of a series of columns that I have agreed to write about singleuse manufacturing technologies and issues for BioPharm International and Pharmaceutical Technology Europe (PTE), which are sister publications. I want to start by acknowledging former BioPharm Editor-in-Chief Laura Bush, who invited me to contribute and to welcome Editorial Director Michelle Hoffman, with whom I look forward to working with. I also want to acknowledge Andrew Sinclair and Miriam Monge, who edited this column in BioPharm over the past several years and who have set a high bar.
Jerold Martin
I've written several editorials and articles for BioPharm and PTE in the past, and I am also a member of the editorial advisory boards for both of these publications. For those who are not familiar with me, I've been in the biopharmaceutical industry for more than 31 years and have worked in filtration process development and validation with many pharmaceutical and biotech companies since before the biotech revolution. As an active member of the Parenteral Drug Association (PDA), the International Society for Pharmaceutical Engineering (ISPE), the American Society for Mechanical Engineering–BioProcess Equipment Committee (ASME–BPE) and the Bio-Process Systems Alliance (BPSA), I've been a contributor or reviewer on numerous industry guides and standards, and have conducted training for regulatory agencies in the Western hemisphere, Europe, and Asia. In my present role as chairman of the board and the Technology Committee of the BPSA, I have had the opportunity to interact with suppliers and users of single-use technologies worldwide and look forward to sharing that perspective here.
Over the past 10 years or so, we've seen singleuse technologies explode from production-scale filter capsules, tubing, and simple biocontainers to encompass sterile connectors, membrane-chromatography adsorbers, bioreactors, mixers, and integrated platform systems with increasing levels of sensors and automated controls. Many articles have been published, and singleuse conferences have become regular events, with topics evolving from fundamental technologies to user evaluations, and on to process and facility integration.
The main issues today include implementation, quality, security of supply, regulatory expectations, system design, integrity/installation testing, QbD, PAT, quality agreements, standardization, disposal and environmental issues, and economic justification. As this column progresses, let me know what singleuse issues and topics you would like to see further explored. This month, I will touch on some recent developments in standardization and quality agreements, and provide an update about some of the latest BPSA initiatives in this area.
Standardization of singleuse components has become a frequent topic in articles, on chat boards, and at conferences. Interest has been expressed in standardizing the materials for films and tubing, as well as the dimensions of sterile connectors, hose barb, and sanitary flange fittings. When considering standardization of singleuse components, it is important to bear in mind that although some aspects of singleuse components can be standardized (e.g., approaches to sterilization, characterization of extractables, particle and endotoxin testing, tubing ID, hose barb, and flange dimensions), it is unlikely that any materials or design features will become a commodity subject to standardization because of the proprietary nature of many singleuse components. Other than ASME–BPE and ASTM International, none of the primary industry professional or trade associations (PDA, ISPE, and BPSA) or regulatory bodies issue formal standards. Pharmaceutical standards bodies, such as the US or European Pharmacopoiea or the International Organization for Standardization, tend to focus on the final drug product and packaging. These can be extrapolated or adapted to singleuse equipment, but the industry organizations themselves primarily issue best practice recommendations and technical guides rather than formal or obligatory standards.
One of the key roles of BPSA, in addition to producing its own best-practice guides, is to stimulate other organizations to also develop guides or standards that facilitate implementation of singleuse equipment. For example, BPSA recently submitted a letter to ASME, encouraging a review of the ASME–BPE standard for sanitary flange fittings with regard to using polymeric material instead of traditional metal alloys. The current ASME–BPE standard for sanitary flanges was developed with stainless steel in mind and specifies dimensions and tolerances that are costly to achieve in a variety of polymers. A modified standard addressing the properties of polymer-based flange connectors that maintains critical fitment requirements, while accommodating the unique properties of molded polymers, could reduce cost of ownership and ensure that all parts can work with singleuse and stainless steel systems. For flange-connector manufacturers, tooling and production costs also could be reduced if more liberal tolerances were allowed.
Many singleuse systems integrators now offer standardized singleuse assembly configurations for common functions, or subassemblies that can be custom assembled aseptically with sterile connectors by the user. Such rationalization can help reduce complexity and cost, but further standardization of designs or materials among suppliers is practically difficult and would be a barrier to further product development. Singleuse technology may have moved out of its infancy, but standardization to create commodities needs to be considered very carefully. Establishing standards for equivalency of designs or materials would stifle innovation and conflict with market demands for improved designs and materials.
STANDARDIZING QUALITY AGREEMENTS
One area that can benefit from a form of standardization is quality agreements. In a recent editorial I wrote for PTE (October 2010; available at www.pharmtech.com/jmartin), I discussed a new initiative by BPSA to develop a quality agreement template for singleuse suppliers and users. The FDA has provided guidance on establishing quality agreements with contract manufacturers of licensed biologics, and drug manufacturers are seeking similar agreements with all their suppliers, including equipment suppliers.1 The Society of Chemical Manufacturers and Affiliates, home to BPSA, has a Bulk Pharmaceuticals Task Force that has developed a template for quality agreements related to the manufacture and release of substances regulated by the FDA.2 A similar template has been developed by the International Pharmaceutical Consortium on Regulation and Science for use by drug manufacturers and suppliers when addressing raw materials, container closure/device components and packaging materials.3 BPSA, through its Singleuse System Quality Agreement Template Task Force, is adapting the content of these guides to develop a template specific to singleuse manufacturing. This template is intended to simplify and standardize the timeconsuming and sometimes difficult process of negotiating quality agreements between biopharmaceutical or vaccine manufacturers and singleuse system or component suppliers.
To discuss this topic further and provide an opportunity for users and suppliers to offer input, BioPharm and BPSA are collaborating to produce a web seminar on quality agreements for single-use manufacturing. The seminar is scheduled for Wednesday Mar 2, 2011 (7 am PST, 10 am EST, 3 pm GMT, and 4 pm CET). For more details, see: http://biopharminternational.findpharma.com/webcasts.
BPSA also will be hosting its inaugural International SingleUse Summit in Washington DC (Jul 27–29, 2011). The meeting will focus on the future of biopharmaceutical manufacturing, with a specific emphasis on regulatory considerations and perspectives on the effect of healthcare reform on drug markets. Innovations and market drivers affecting the singleuse industry also will be discussed. More information is available at www.bpsalliance.org.
In my next column, I'll be reporting on global issues, as well as on the implementation of singleuse components, based on participation as a speaker and panelist at several international meetings, including the ISPE Japan Sterile Products Processing Community of Practice in Japan (Feb 17, 2011), the ISPE Aseptic Processing Seminar in Tampa, Florida (Feb 21–22, 2011), and the IBC Biomanufacturing and SingleUse Systems Asia Conference in China (Mar 7–9, 2011).
In the interim, feel free to send me suggestions about topics, issues, and technology that affect your implementation of single-use technology. I look forward to hearing from you.
Jerold Martin is senior VP of global scientific affairs, Biopharmaceuticals, Pall Life Sciences, Port Washington, NY, and chairman of the Board and Technology Committee of the BioProcess Systems Alliance (BPSA), 516.801.9086, jerold_martin@pall.com.
REFERENCES
1. US Food and Drug Administration. Guidance for industry. Cooperative manufacturing arrangements for licensed biologics. Rockville, MD; 2008 Nov. Available from: www.fda.gov.
2. SOCMA BPTF. Manufacturer's quality agreement template. 2010 Apr. Available from: www.socma.com.
3. IPAC-RS. Quality agreement template toolkit. 2009 May. Available from: www.ipacrs.com.
