Overcoming the challenges of high concentration protein formulations

There is a trend within the biopharmaceutical industry for companies to develop formulations for protein drugs with extremely high concentrations. Such formulations provide advantages to both patients and clinicians as they allow biological drugs to be delivered via the sub-cutaneous route of administration rather than by the more traditional intravenous route. Sub-cutaneous delivery allows patients to receive treatment in a clinic or even administer the drug themselves while intravenous infusions tend to require the patient to make a hospital visit which increases the cost of treatment. However, if a patient is able to self-administer the pharmaceutical drug they require to treat a chronic disease then they are more able to lead a normal life which is a tremendous benefit (Highly concentrated protein formulations: Finding solutions for the next generation of parenteral biologics, J Kling, 2014).

The challenge of processing highly concentrated protein drugs

Being able to provide a biopharmaceutical at a formulated concentration of 100 g/L or higher can be a means by which biopharmaceutical companies can gain an advantage over one another in an increasingly competitive marketplace. However, developing such formulations is no trivial task because at high concentrations, protein solutions can become very viscous and difficult to process and the proteins themselves can aggregate. The viscosity of these solutions can challenge filtration equipment and can lead to significant yield losses in the final stages of the processes when the product has its greatest value. Protein aggregation can lead to a reduction in the pharmaceutical’s potency and can even trigger an immune reaction to the drug.

Innovation at the interface with formulations

The topic of high concentration protein formulations will be covered at the BioProcess International Conference & Exposition 2015 to be held on October 26-29 in Boston, MA. Sigma S Mostafa, PhD, Director, Process Development at KBI Biopharma Inc will be chairing a session on ‘Innovation at the Interface with Formulations’. Pfizer are scheduled to present on ‘Challenges of High Concentration Formulations – Dealing with Viscosity and Excipients’ while Mark Moody will present on ‘Opportunities and Challenges of High Concentration Biologics: Case Studies’. The session promises to address some of the key issues manufacturers face when processing concentrated protein solutions.

Have your say

Protein biopharmaceuticals are being formulated to 100 g/L even 200 g/L, however, some have proposed that concentrating to 500 g/L may be desirable. In your opinion, what is the maximum concentration that is required or attainable for protein drug formulations?

Dr Nick Hutchinson

Join me at #BPIconf

Contact me at nick.hutchinson@parker.com

Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.

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Single-Use Standardization on the agenda for BPSA at BPI Boston, 2015

“The BioProcess International Conference has always been a good venue for the Bio-Process Systems Alliance to work with industry to identify issues and define next steps”, say Todd Kapp, BPSA Board Member and Sales & Market Development Manager of Parker domnick hunter – North America.

The Bio-Process Systems Alliance is a leading trade association which facilitates the implementation of single-use bioprocessing through networking opportunities, creating a safe harbour for dialogue between industry and business leaders, providing forums for end-users and suppliers to work together and producing best practice guides.

“The BPSA has become a recognized leader in the industry for bringing users and suppliers of single-use technology together to discuss and educate one another on best practices and guidelines for implementation”, Kapp observes.

Single-Use Standardization

Along with other industry organizations such BPOG, PDA, ASTM and ASME BPE they will be participating in a Town Hall Forum Discussion on Single-Use Standardization at the BioProcess International Conference andExposition 2015 in Boston.

Standardization of single-use assemblies is an objective for many biomanufacturing organizations as they seek to reduce inventories and working capital. Historically, standardization exercises within the processing industries have been somewhat protracted affairs as various players try and agree on the preferred solution to standardize upon.

Todd Kapp (Parker domnick hunter & BPSA Board Member) 

EPICSolutions™ for Single-Use Technologies

Successfully implementing single-use technologies into biomanufacturing processes raises a number of issues that end-users are having wrestle with including the safety of the materials used, whether they shed particles or can maintain integrity and an increased reliance on the quality systems of their suppliers including their change notification procedures.

To help end-users address these issues the BPSA will be leading or contributing to sessions along the theme of EPICSolutions™ which stands for Extractables, Particles, Integrity, Change and Sustainability and was the main theme of the BPSA Summit held in Washington DC last week.

Kapp explains, “BPI has been and continues to be a great way for BPSA to communicate with the market and spread the word about the value it brings to industry”.

Without doubt BPI will be a richer learning experience for bioprocess engineers on their journey to implement single-use technologies by the inclusion of the BPSA in the program.

Dr Nick Hutchinson

nick.hutchinson@parker.com

Join me at #BPIconf

Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.

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BDP Week 2015: Extractables and Leachables

By: Maribel Rios, Managing Editor of BioProcess International

On Tuesday afternoon, 31 March 2015, the single-use track of the BioPharmaceutical Development and Production (BDP) Week meeting in Huntington Beach, California, focused on the challenges associated with particles and extractables and leachables (E&L). Bobbijo V. Redler, PhD (Merck & Co., Inc)  began by defining the terms and the different types of E&L studies, including controlled extraction studies (screening), simulation studies, leachables testing (using methods validated for registration), and routine monitoring (also using validated methods). She reviewed simulated study designs, the use of various analytical techniques for E&L studies, and efforts of the E&L team of the BioPhorum Operations Group (BPOG).

James Vogel (The BioProcess Institute) presented on the work of the Bio-Process Systems Alliance (BPSA) on its 2014 particulates technical guide, “Recommendations for Testing, Evaluation, and Control of Particulates from Single-Use Processing Equipment.” The 12-chapter compendium is targeted for both end users and supplies of single-use components and systems. The session ended with a roundtable moderated by Redler. Panelists included Weibing Ding (Biogen Idec), James Vogel, and Michael Rupperto, PhD (Material Needs Consulting). The session consisted of a Q&A with attendees. Various issues were discussed, including the following:

·         Whether the BPOG extractables protocol published last year (Ding W, et al. Standardized Extractables Testing Protocol for Single-Use Systems in Biomanufacturing. Pharm. Eng. Nov-Dec. 2014) actually is a “best practices” document and if it truly can be used for “comparability.” Panelists said that the protocol does provide some flexibility, the document is a “step forward,” and that ASTM (Association for Standards Testing and Materials) and USP (US Pharmacopeia) Chapter <661.3> work is ongoing.

·         Whether it is better to discontinue use of a component is easier than to conduct continuous monitoring for extractables. The panel answered that the decision is often a matter of time and cost and that the material may have unique properties that are needed.

·         How to determine a threshold for extractables information and the definition of BPA-free. The panel emphasized the importance of smart material selection, paying close attention to materials, including secondary packaging, and continually assessing risk.

·         Whether the BPOG protocol (above) should actually be more rigorous. The panel mentioned that not many company are conducting in-process leachables testing for process equipment, reminding attendees that suppliers are responsible for extractables tests and end users are responsible for leachables testing. The general intention is to get single-use implemented quickly. 

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Views on the exclusivity period of biogenerics

Bio and GPhA have released statements about the twelve year exclusivity period that was amended by the Senate Committee on Health, Education, Labor, and Pensions (HELP) for biologics last week.

Bio stated “the HELP Committee has embraced our long held belief that a minimum of 12 years of data exclusivity establishes a fair and reasonable period to ensure continued biomedical innovation and provide the benefits of expanded competition.”

GPhA President and CEO Kathleen Jaeger claimed that her company would “continue to fight in the House to ensure a true balance is achieved between innovation and competition.”

For a more in-depth look at the reactions, read here.

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