Risk-Based Implementation of Single Use Systems

Implementing Single Use Systems

Stephen Brown
Contributor: Stephen Brown
Posted: 06/30/2011

The deployment of Single Use Systems (SUS) has become a hot topic within the biopharmaceutical industry. From its origins in filtration technology and blood containers, the technology has developed rapidly. In the last couple of years and in response to end-user demand, all of the major suppliers have improved their capabilities and technology offering and it’s now possible to exploit single-use technology for practically all upstream and downstream bioprocess and fill and finish operations (for an example, see Figure 1).

In this occasional series we will address the different themes and points to consider which are key to the implementation of these revolutionary and innovative new manufacturing systems, starting with an Implementation Plan.

So what’s so revolutionary and innovative? The Revolution. In a few words, a Single-Use System or SUS, consists of polymer-based fluid handling systems ie tubing, connectors and reservoirs which replace classical stainless steel equipment or components, which here we will call Multiple Use Systems (MUS). The Innovation. Freedom to organise your manufacturing strategy and equipment in a manner that best fits the process knowledge, escaping the previous paradigm with MUS, of, “one size fits everything”. It’s really a smarter way to new product development.

Figure 1. Nucleo 250 l bioreactor with its single use bioprocess container. This is a single use bag integrating an internal paddle mixing and sparger system from ATMI. As the photo on the right shows, single-use bioreactor bags have become complex, in consequence. a comprehensive risk-based Implementation Plan is essential to the timely and technically sound exploitation of Single Use Systems. Photos source : Pierre Guerin (DCI Biolafitte in the USA) and ATMI.

But what about technical and regulatory guidance and standardisation for SUS ? For industry (suppliers, vendors and end-users) and regulators alike that’s an issue. Help with implementing SUS is on its way. Parenteral Drug Association (PDA) has a task force in the final stages of preparing a technical report on this subject. At a well-attended workshop in Bethesda, June 22-23, PDA gave participants an opportunity to meet with the task force in order to review the technical report1,2, with publication planned for end 2011.Chaired by Robert Repetto (Pfizer) and Morten Munk (CMC Bio), the PDA Single Use Systems Task Force was organised to include end users, suppliers, industry enablers and regulators, in order to provide a balanced, well vetted and consensus driven viewpoint for the technical report. The philosophical basis of approach is based on QbD principles with a detailed science and technology driven look at manufacturing strategies, technologies and system integration, business drivers, qualification and implementation.

Other professional and standards organizations such as the Bio-Process Systems Alliance (BPSA), ISPE and ASME-BPE are also working on technical aid and standardisation issues are discussed here3. If you’re not up on all the jargon or are looking for some basic definitions, the best source I’ve found can be read in the FAC on the BPSA website4.

As previously mentioned a comprehensive risk-based approach is essential for the timely and technically sound exploitation of Single Use Systems. The Pierre Guerin Nucleo 250 l bioreactor hardware with its ATMI single use bioprocess container (Figure 1) has been installed at Vivalis CMO for therapeutic protein manufacturing. Whilst SUS design concepts are different to classical stainless steel MUS bioreactors, the Nucleo bioreactor offers comparable functionality to classical stirred tank bioreactors5. At Vivalis, we have used a risk management approach to SUS Implementation6 and in our experience the Nucleo provides a good environment for cell culture with cell substrates such as the duck EB66®. The ATMI bag, with its TK-8 film contact surfaces and paddle and connectors are all decontaminated and easily discarded after use, providing a large gain in efficiency and campaign productivity.

The different stages in SUS implementation can be envisaged as a roadmap accessed via a series of checkpoints. Important points to consider throughout these different stages are best addressed according to the main themes of Stakeholder Management, Risk Management and Process Validation and Verification. The implementation process can be adapted according to the level of detail addressed during the conception or manufacturing strategy phase and as a function of your projects position within the product life cycle. The level of risk management applied will also be adapted according to the level of complexity of the issues or subjects.

The purpose of the Project Implementation Plan is to define and describe the project execution strategy, how the project will be managed and how compliance is addressed in order to ensure that the project meets its goals in terms of budget, time and Quality. Typically the Implementation Plan will cover the following.

Introduction Overview Deliverables Scope Project Management Organisation Project Execution Approach Quality Issues Risk Management Health, Safety and Environment Plan Commissioning and Qualification Handover Abbreviations and References


Table 1
. Suggested contents for a risk-based Single Use Systems Implementation Plan (read l to r).
The final form of the implementation plan will depend on the strategy and business drivers employed and may vary from the suggestions given above. As always, and as per Quality Risk Management (QRM)7, the evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient. The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk.

That completes our brief look at a SUS Implementation Plan. Over the next few columns, we will discuss some of the key issues in implementation, starting next time, with stakeholder management.



References

  1. PDA Single Use Systems Workshop, Bethesda USA, June 22-23, 2011.
  2. Technical Report, Concepts and Themes, Robert Repetto, Pfizer, PDA Single Use Systems Workshop, Bethesda USA, June 22-23, 2011.
  3. Trends Towards Standardization, Jerold Martin, BioPharm International.com, Feb 1, 2011, Volume 24, Issue 2, pp. 23-24.
  4. Bio-process Systems Alliance FAC : http://www.bpsalliance.org/faq.html
  5. Comparing Fed-Batch Cell Culture Performances of Stainless Steel and disposable Bioreactors, A Poles Lahille etal., BioPharm International.com, Jan 1, 2011.
  6. A Risk-Based Approach to Single Use Systems Selection and Implementation for IMP Manufacture, Stephen Brown, Vivalis, Informa Bioproduction 2010 - Disposables for Biopharmaceutical Manufacturing, October 27, 2010.
  7. Quality Risk Management; ICH, 2005.


 

Stephen Brown
Contributor: Stephen Brown
Posted: 06/30/2011

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