Trends Towards Standardisation

This is the first of a series of columns that I have agreed to write on single‑use manufacturing technologies and issues for BioPharm International (BPhI) and Pharmaceutical Technology Europe (PTE), which are sister publications. I want to start by acknowledging former BPhI Editor Laura Bush, who invited me to do this, to welcome Senior Editor Michelle Hoffman, and to thank Managing Editors Chitra Sethi (BPhI) and Fedra Pavlou (PTE), whom I look forward to working with. I also want to acknowledge Andrew Sinclair and Miriam Monge, who did a great job with this column in BPhI over the last several years and who have set a high bar in passing the baton.

I’ve written several editorials and articles for both BPhI and PTE in the past, and I am also a member of the Editorial Advisory Boards for both of these publications, but for those who are not familiar with me, I’ve been in the biopharmaceutical industry for over 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, more recently, the Bio-Process Systems Alliance (BPSA), I’ve been a contributor or reviewer on numerous industry guides and standards, and have conducted trainings 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.

During 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.

Jerold Martin

The main issues today include: implementation, quality, security of supply, regulatory expectations, system design, integrity/installation testing, QbD, PAT, quality agreements, standardisation, disposal and environmental issues, economic justification, and many more. 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 standardisation and quality agreements, and provide an update on some of the latest BPSA initiatives in this area.

Standardisation of singleuse has become a frequent topic in articles, on chat boards and at conferences. Interest has been expressed for standardising materials for films and tubing, as well as the dimensions of sterile connectors, hose barb and sanitary flange fittings. When considering standardisation of singleuse components, it is important to bear in mind that while some aspects of singleuse can be standardised (e.g., approaches to sterilisation, characterisation 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 standardisation because of the proprietary nature of many singleuse components. Other than ASMEBPE or 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 Pharmopoiea or the International Organization for Standardization (ISO), tend to focus more on the final drug product and packaging. These can be extrapolated or adapted to singleuse equipment, but the industry organisations themselves primarily issue best practice recommendations and technical guides rather than formal or obligatory standards.

One of the key roles of the BPSA, in addition to producing its own best practice guides, is to provide stimulus to other organisations to also develop guides or standards that facilitate singleuse equipment implementation. For example, the BPSA recently submitted a letter to the 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 ASMEBPE 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 involved parts can interwork with both singleuse and stainless steel systems. For flange connector manufacturers, tooling and production costs could also be reduced if more liberal tolerances were allowed.

Many singleuse systems integrators now offer standardised singleuse assembly configurations for common functions, or subassemblies that can be customassembled aseptically with sterile connectors by the user. Such rationalisation can help reduce complexity and cost, but further standardisation of designs or materials among suppliers is both practically difficult and would be a barrier to further product developments. Singleuse technology may have moved out of its infancy, but standardisation to create commodities needs to be considered very carefully. Establishing standards for equivalency of designs or materials would stifle innovation and be counter to market demands for improved designs and materials.

Standardising Quality Agreements

One area that can benefit from a form of standardisation 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 the 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.¹ The Society of Chemical Manufacturers and Affiliates (SOCMA), home to the 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 (IPAC-RS) for use by drug manufacturers and suppliers when addressing raw materials, container closure/device components and packaging materials.³ The 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 is intended to simplify and standardise the otherwise timeconsuming and sometimes difficult process of negotiating quality agreements between biopharm or vaccine manufacturers and singleuse system or component suppliers.

To further discuss this topic and provide opportunity for users and suppliers to provide input, BPhI and the BPSA are collaborating to produce a web seminar on Quality Agreements for single use manufacturing. The seminar is scheduled for Wednesday 2 March (7 am PST; 10 am EST; 3 pm GMT, 4 pm CET). For more details, see: http://biopharminternational.findpharma.com/webcasts

The BPSA will also be hosting its inaugural International SingleUse Summit (ISUS) in Washington DC (USA; 27–29 July). The meeting will focus on the future of biopharmaceutical manufacturing, with a specific emphasis on regulatory considerations and perspectives on the impact of healthcare reform on drug markets. Innovations and market drivers affecting the singleuse Industry will also be discussed. More information is available at www.bpsalliance.org.

In my next column, I'll be reporting on global issues, as well as the implementation of singleuse based on participation as a speaker and panelist at several international meetings including the ISPE Japan Sterile Products Processing Community of Practice Meeting in Japan (17 February), the ISPE Aseptic Processing Seminar in Tampa (Florida, USA; 21–22 February) and the IBC Biomanufacturing and SingleUse Systems Asia Conference in China (7–9 March).

In the interim, feel free to send me suggestions on topics, issues and technology that impact your implementation of single-use. I look forward to hearing from you. jerold_martin@pall.com

Jerold Martin is Senior VP of Global Scientific Affairs at Pall Life Sciences, Biopharmaceuticals Group, and Chairman of the Board and Technology Committee of the BioProcess Systems Alliance (BPSA). He is also a member of Pharmaceutical Technology Europe's Editorial Advisory Board. jerold_martin@pall.com

References

1. FDA, Guidance for Industry: Cooperative Manufacturing Arrangements for Licensed Biologics (November 2008). www.fda.gov

2. SOCMA BPTF, Manufacturer's Quality Agreement Template (April, 2010). www.socma.com

3. IPAC-RS, Quality Agreement Template Toolkit (May, 2009). http://ipacrs.com