1 RESIN SOURCING SUMMARY Many biopharmaceucal processes are maturing, and manufacturers are seeking to make modificaons and improvements to those processes as market forces exert greater pressure on costs. At the same me, there have been considerable advances in processing technology and there are opportunies to create value and reduce costs by incorporang those technologies. Finally, some of the new technologies show performance comparable to current industry standards and there is the opportunity to reduce the risk of reliance on a single source for crical materials. This paper discusses the regulatory pathways for introducing process improvements and/or alternate sources of chromatography resins, and provides selected examples of the approaches taken by different manufacturers. INTRODUCTION The use of raw materials and processing aids in pharmaceucal manufacturing is subject to regulaon by the various licensing authories, and these authories require noficaon of any changes to manufacturing processes for licensed products. For many years, companies have performed process changes on approved products in the USA using the Comparability Protocol (1). Typically, these consist of a group of changes, rather than incremental improvements, since there is a significant administrave and logiscal burden in dealing with mulple jurisdicons (2-4). The protocol is discussed with the agency to determine if (a) it meets expectaons to jusfy making the changes and (b) to determine the appropriate noficaon approach (see below). Change is ancipated as technology advances are made. License holders are encouraged to implement connuous improvements across a product’s lifecycle through the use of both science- and risk-based approaches. Periodic review of process performance and product quality during management reviews over the lifecycle of a product can be used to make improvements when understanding has advanced with experience to jusfy the proposed changes (5). The procedures for implemenng change will depend on a variety of reasons as part of product lifecycle management (PLM), which can include (but are not limited to): • The extent or magnitude of the changes • The nature of any addional changes being implemented at the same me (e.g. upstream, downstream, analycal tesng, scale-up, scale-out/number-up, site transfer) • The perceived risk • Jusficaon for the changes Steps are not necessarily sequenal and can be run concurrently. Brian Hubbard 1 & Duncan Low 2 1 CMC Bioprocess Consulng LLC, 8 San Juan Ranch Rd, Santa Fe, NM 87506 2 Claymore BioPharm LLC, 14360 Temple Lane, Culpeper VA 22701 Resin Sourcing
Transcript
1 RESIN SOURCING
SUMMARY
Many biopharmaceutical processes are maturing, and manufacturers are seeking to make modifications and improvements to those processes as market forces exert greater pressure on costs. At the same time, there have been considerable advances in processing technology and there are opportunities to create value and reduce costs by incorporating those technologies. Finally, some of the new technologies show performance comparable to current industry standards and there is the opportunity to reduce the risk of reliance on a single source for critical materials.
This paper discusses the regulatory pathways for introducing process improvements and/or alternate sources of chromatography resins, and provides selected examples of the approaches taken by different manufacturers.
INTRODUCTION
The use of raw materials and processing aids in pharmaceutical manufacturing is subject to regulation by the various licensing authorities, and these authorities require notification of any changes to manufacturing processes for licensed products.
For many years, companies have performed process changes on approved products in the USA using the Comparability Protocol (1). Typically, these consist of a group of changes, rather than incremental improvements, since there is a significant administrative and logistical burden in dealing with multiple jurisdictions (2-4). The protocol is discussed with the agency to determine if (a) it meets expectations to justify making the changes and (b) to determine the appropriate notification approach (see below).
Change is anticipated as technology advances are made. License holders are encouraged to implement continuous improvements across a product’s lifecycle through the use of both science- and risk-based approaches. Periodic review of process performance and product quality during management reviews over the lifecycle of a product can be used to make improvements when understanding has advanced with experience to justify the proposed changes (5).
The procedures for implementing change will depend on a variety of reasons as part of product lifecycle management (PLM), which can include (but are not limited to):
• The extent or magnitude of the changes• The nature of any additional changes being implemented at the same time (e.g. upstream,
downstream, analytical testing, scale-up, scale-out/number-up, site transfer)• The perceived risk• Justification for the changes
Steps are not necessarily sequential and can be run concurrently.
Brian Hubbard1 & Duncan Low2 1 CMC Bioprocess Consulting LLC, 8 San Juan Ranch Rd, Santa Fe, NM 875062 Claymore BioPharm LLC, 14360 Temple Lane, Culpeper VA 22701
Resin Sourcing
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REGULATORY CONSIDERATIONS
RISK ASSESSMENT
The first task in a science and risk-based process is to understand the risks associated with making the change (5), since the product may not be comparable after the change is made. This assessment should determine the effect the proposed changes have on the identity, strength, quality, purity, and potency of a drug product or a biological product.
1. REGULATORY & TECHNICAL CONSIDERATIONS
Figure 1. Overview of regulatory and technical activities
REGULATORY
TECHNICAL
MONITORING &CONTINUOUS IMPROVEMENT
Process PerformanceMonitoring
Non-ConformancesDeviations
CAPAs
Mitigation
ProductLife Cycle
Management
Change Justification
Identify Established Conditions
Reporting Approach
PAS/CBE30/CBE
PACMPComparability
ProtocolImplement
QualityAttributes
Process ParametersCriticality
Analytical MethodsControls
DownstreamCapacity Stability
TRIGGERS FOR CHANGE
A license holder may consider process changes in anticipation of planned events (e.g. site transfer, equipment upgrade, scale-up, process improvements in quality, titer or robustness, technology developments, changes in regulatory requirements) or in response to unplanned events (discontinuation of a key raw material, supply disruption, geopolitical events, quality/performance issues, contamination). In the former case the license holder can take a structured approach to implementing the change, and will in all likelihood co-ordinate and consolidate changes in a systematic manner, rather than make them incrementally, given the administrative burden discussed above. An exception would be if changes are required as a consequence of a corrective action/preventive action (CAPA) process requiring immediate action.
A structured approach can be taken for certain forced changes, provided sufficient advance notice is given e.g. discontinuation of a raw material.
This document focuses on what would be required for a change to a chromatography resin. The first part of this paper covers regulatory and technical considerations relating to the manufacturing process (Fig.1). The second part provides additional consideration that may arise as a consequence of the changes.
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Generally speaking, upstream changes are more impactful than those made downstream, however there is the potential to impact size/structural variants of product and process related impurities (4). In the case of monoclonal antibodies, which are amenable to a platform approach (6), understanding and information developed from changes made to one process may (in certain cases) be used to support changes made to related processes (4).
REPORTING CHANGES
Before embarking on process changes, it is important to determine the regulatory process and requirements for reporting the changes. The FDA uses three tier-based types of report (3, 7, 8):
1. Prior approval supplement (PAS) - changes that have a substantial potential to have an adverse effect on product quality (i.e. major changes). Requires prior approval prior to distribution of product.
2. Changes Being Effected in 30 days/ Changes Being Effected Supplements (CBE30/CBE) - changes that have a moderate potential to have an adverse effect on product quality (i.e. moderate changes)
3. Annual report (AR) – changes that have a minimal potential to have an adverse effect on product quality (i.e. minor changes).
A ‘new or revised purification process, including a change in a column’ is given as an example of a change requiring a PAS (7). A more recent guidance for specific biologics (not including e.g. monoclonal antibodies for in vivo use and therapeutic recombinant-DNA derived products), it specifically cites a change in resin material as requiring a PAS (8).
In summary, a resin change would typically be viewed as requiring a PAS. Note that this could be relaxed to some extent based on discussion with the appropriate authorities and on the extent of the resin change (like-for-like, a minor change still functionally similar, or a different modality). A resin change to additional licensed molecules as part of a platform process, however, may only require a CBE30/CBE based on platform understanding and prior knowledge (see following examples).
ASSESSMENT AND IMPLEMENTATION OF CHANGES
In general, the proposed changes must be assessed, documented and justified so that the company can demonstrate that it has sufficient knowledge to prepare and manage the impact of the change. This should be documented and provided to the relevant agency for approval prior to implementation. For a supplement (PAS, CBE30, or CBE) this includes: • A detailed description of, including a rationale for, the change• The product(s) involved• The manufacturing site(s) or area(s) affected• A description of the method(s) used, and the studies performed to evaluate the effects of the
change on the product quality, and data derived from these studies (Comparability Protocol, CP)• Relevant validation protocols and data• A reference list of relevant standard operating procedures
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COMPARABILITY PROTOCOL
A comparability protocol is a comprehensive, prospectively written plan for assessing the effect of proposed CMC post-approval changes on the identity, strength, quality, purity, and potency of a drug product or a biological product (i.e., product). It can be submitted prospectively with the original application or as part of the PAS. Approval of the original application containing the CP or a subsequent PAS containing the CP can provide an applicant with an agreed-upon plan to implement the specified changes, and in many cases, a justification to report the change(s) in a decreased reporting category (7, 8). The EMA also adopts a tiered approach to change (3, 9 - 11):
• Type II – may have a significant impact on the quality, safety or efficacy of a medicinal product• Type IB – a minor variation, default if change does not fall into another category• Type IA, IAIN – no, or minimal impact
A ‘substantial change’ which ‘may have a significant impact on the quality, safety or efficacy of a medicinal product’ is listed as a Type II change, as is a change which may require assessment of ‘comparability of a biological/immunological product’ (9).
POST-APPROVAL CHANGE MANAGEMENT PROTOCOL (PACMP)
The PACMP is similar in concept to the CP. It provides predictability and transparency regarding the requirements and studies needed to implement a change. It also requires approval by the regulatory authority, and the conditions and acceptance criteria outlined in the protocol must be met in order to implement the change (11).
• Justification that there is a recognized future need• A detailed description of the proposed change• Risk assessment of the impact of the change• Discussion of the approved control strategy to identify and manage risks• Description of the studies to be performed, and the test methods• The approach to be used to demonstrate comparability
QUALITY BY DESIGN
Regulators have advocated the use of Quality by Design for the development and management of post-approval changes (12). A systematic approach to process characterization is taken, which begins with risk assessment and prioritization, process modeling and characterization and the setting of acceptance criteria. This leads to the development of a design space, within which satisfactory product quality is achieved (5, 12 – 15). Once established, this gives a manufacturer flexibility to make changes within the design space, since movement within an approved design space is not considered a change (from a regulatory filing perspective) (4, 16).
RISK ASSESSMENT
This assessment should identify the critical quality attributes (CQA’s), the Key Process Parameters (KPP’s) that are used to manage/control them, and downstream controls that can mitigate any limitations of a given unit operation of the process (e.g. removal of product or process related impurities).
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In 2008, an initiative was taken by Subject Matter Experts (SME’s) from several manufacturers to develop a case study (17) to advance the principles contained in ICH Q8 (R2), ICH Q9 and ICH Q10. The case study provides comprehensive guidelines on process development of a hypothetical antibody process in a Quality by Design framework. Specific details of both chromatography capture steps and purification steps are provided. This case study provides guidelines for the qualification of a scale down model, gives an approach to risk assessment of the steps (outlined in Figure 2), describes the design of multivariate and univariate studies, and reuse/resin lifetime studies.
The process is based on a three-step purification and also provides recommendations for changes to the affinity capture step (Protein A) and changing to alternative formats for anion exchange, and is further discussed in the section ‘Technical Approach’.
ICH Q12
ICH Q12 is currently in draft form but reflects future thinking on change management as part of PLM (18). It is intended to promote innovation and continual improvement in the biopharmaceutical sector, and provides a framework to facilitate the management of post approval changes. Specifically, in certain ICH regions, it is ‘not fully compatible with the established legal framework with regard to the use of explicit Established Conditions’ (ECs) (18). ECs are legally binding information (or approved matters) as part of a filing that are considered necessary to assure product quality (18).
As a consequence, any change to ECs necessitates a submission to the regulatory authority. A decision tree for identification of ECs is given in (18), see figure 3, and examples of ECs are provided in (19). For a fuller discussion of the approach see the original documents.
Is the parameter either a CPP or KPP?
It is an EC It is not an EC
Not reported
Reporting categories for changes to EC
What is the level of risk associated
with the proposed change?
Prior Approval Notification
NOYES
HIGH MODERATE / LOW
Figure 3: Decision tree for identification of ECs (modified from ICH Q12)
Figure 2: Risk assessment approach used through A-MAb Development Life Cycle
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IDENTIFICATION OF ECs
ICH Q12 discusses 3 alternative approaches that can be used separately or in combination to identify ECs:
• A parameter-based approach, based on an understanding of the relationship between inputs and resulting quality attributes
• An enhanced approach, with increased understanding of interaction between inputs, attributes and controls
• A performance-based approach based on control of outputs rather than inputs
REVISION OF ECs
The options for revisions include post-approval submissions or through a Post-Approval Change Management Protocol (PACMP), filed either with the original application or as part of a post-approval regulatory submission. The PACMP should address the change in the context of the impact on ECs, bearing in mind ECs for a given unit operation may not be the same from one process to another. For example, a manufacturer may or may not make a claim for viral clearance for a Protein A step.
TECHNICAL APPROACH
The studies which are required will depend on the degree to which one resin differs from another, and depends on the choices under consideration (changes within a modality, changing the sequence of steps, changing to a different modality). The list provided below (Table 1.) gives some examples for a Protein A resin. It is not an exhaustive list, since a large number of combinations are possible, in particular when it comes to variants of Protein A which have been engineered to improve their usability (e.g. resistance to high pH cleaning, reduced non-specific binding, improved binding characteristics through ligand orientation and multimerization, change in resin base matrix to improve pressure flow characteristics, gentler elution conditions). This is a competitive area and suppliers have used various strategies and engineered different sub-units of Protein A to circumvent intellectual property, which leads to the significant diversity (20,21).
The changes in Table 1 can impact the type of studies that may need to be performed to determine the impact to the product and the process:
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Resin Change Example Variables Considerations
Base Matrix Chemistry
- Cross-linked agarose- Cellulose- Control pore glass- Synthetic polymers
*HETP= height equivalent to a theoretical plate (a measure of chromatographic performance)
Table 1. Overview of consequences of a resin change
Similar considerations apply for changes within other modalities (e.g. ion exchange, hydrophobic interaction, mixed mode etc). In general, the more closely an alternative resin resembles the original, the more closely similar the operating conditions are likely to be; however, some modification of conditions may be expected. If a change of modalities (e.g. HIC vs IEX vs affinity) or formats (packed bed vs membrane adsorber) is being considered, then far more characterization would be required to establish comparability.
The A-Mab case study provides a discussion in Section 4.6.1.9., describing the qualification of an alternate source of Protein A resin from a different supplier, in anticipation of technology advances and/or process improvements (17). These studies include:
• Triplicate studies on multiple lots of clarified harvest run at midpoint of test conditions (Comparisons of removal of HCP, DNA, insulin, and ProA leaching)
• Leached Protein A removal by downstream polishing chromatography steps • Multivariate study establishing the new design space (with subtle changes to elution pH, protein
load, etc.) and impact to the CEX design space with regards to HCP clearance. • A full resin reuse study at lab-scale to support the claimed lifetime (250 cycles in this case)• In-process hold study of lab-scale product pools generated from the alternate resin
The majority of these studies can be run in a qualified, scale-down model. Additional studies may be required depending on whether additional changes to the process are being submitted, the extent of these studies will be commensurate with the significance of the change (e.g. changes to upstream,
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There is further discussion of the regulatory approach in Section 7 of the A-Mab case study, where the changes are considered in the framework of Quality by Design and the concept of Design Space. In the case study, two commercial scale lots were manufactured prior to the license application to gather additional data to support the design space. Detailed protocols for both changes are provided in section 7.5
Note that A-Mab is a hypothetical case study, and it does not make the claim that the studies above would be sufficient for a comparability protocol. It is likely that at least some of these studies would need to be verified at scale, and in any case, agreement should be reached with the licensing authority prior to initiating studies. In the protocols in Section 7.5 it is stated in both cases that ‘at scale data will be collected concurrently…”(17).
IMPLEMENTING CHANGE - CASE STUDIES
Authors from Genentech described their approach for implementing post approval changes to Herceptin (22). Their studies were broader than just a change to the chromatography step and included multiple changes both upstream and downstream. Operations covered included reuse, in-process hold times, buffer stability, impurity removal, and accelerated degradation amongst others. ‘Comparable’ was considered as data within +/- 3SD of historical data. The change submission was filed as a PAS, no additional PK studies were required.Implementation of the resin change into other products in Genentech’s portfolio was treated as a CBE, effective immediately due to the platform approach and their extensive experience with it.
Table 2. Attributes which may be impacted by a resin change
sequence of unit operations, equipment design). Table 2 provides a partial list of product quality attributes which may need to be assessed as part of a change.
A similar approach could be taken for the replacement of one ion exchanger resin with another, so long as appropriate consideration is given for other process parameters. The A-Mab case study also discusses a case where the manufacturer plans to replace an anion exchange resin with an anion exchange membrane. The design space for a membrane would be established following the same principles as for a resin, but it would differ in terms of equipment and buffer volumes. Outputs would be similar since the same separation principle is being used. It would require notification since a new material (the membrane) is being used, but the risk would likely be considered low.
Confirm that the material produced with the new resin is within the acceptable range for the old resin, OR is within acceptable ranges after minor process adjustments (e.g. load, flow rate, pH) AND does not exceed the capacity of steps downstream for impurity clearance
Purity and process related impurities
- Microbial - Viral (if claimed)- DNA- HCP- Protein A- Cell culture medium
Other
- Stability- In-process hold times
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Authors from Amgen have reported on post approval changes to the Enbrel manufacturing process (23). A number of changes to the upstream and downstream process were introduced simultaneously using a comparability protocol that was designed in partnership with FDA. One of the downstream changes involved the introduction of an additional chromatographic step to improve product quality. Data from qualified small-scale models, pilot scale runs, and manufacturing scale conformance runs were compared. All predefined acceptance criteria were met, and the CP was approved as a CBE30. The package of changes contained in the CP would have typically been approved under a PAS but by proactively working with FDA on the CP a decrease in reporting category to CBE30 was realized. Biogen is constructing a very large-scale state-of-the-art biologics facility in Solothurn, Switzerland (24), and have made a comparative study of Protein A resins to mitigate supply chain risk. In this example the objective was to qualify an alternative material which could be used interchangeably with the current resin. The following criteria were considered:
• Equivalent drug-substance product quality• Equivalent or better process consistency• Equivalent or better dynamic binding capacity• Equivalent or better selectivity
The objective ‘was to identify a resin with comparable performance under identical operating conditions, even though screening revealed some resins with potentially better performance’. The authors conducted experiments at both bench- and pilot scale (up to 30 cm diameter columns). The authors identified host cell protein (HCP) clearance as one of the key parameters. Regardless of which resin was used for capture, the same general population of HCP’s were propagated into the rest of the purification process. The authors did not identify which resins were evaluated, but did indicate that there were ‘differences in bead composition between the two resins’; which would suggest that at least one of the resins was not agarose based.
Unlike previous examples, this work was performed prior to the initial licensing of the antibody in question. As a result, the authors decided to perform the same late-stage process characterization as for their platform resin. The validation exercise for the platform resin was completed in 2017, while validation of resin 2 is ‘pending for a future manufacturing campaign’ at the full-scale process. The authors concede that this approach is conservative, but believe the data will support interchangeable use of the two resins.
Resins are the primary agent for purification and a change in performance could have a significant impact on product quality and yield (25) and are frequently considered critical, at least initially. As a result the assessment of new materials must extend beyond the material specification to include the supplier’s manufacturing process, quality systems, and sourcing strategy (26).
A change of resin material will in all probability mean a change in supplier, which will in its turn trigger certain additional activities such as audits, due diligence activities, and extend to material characterization activities as well as the process impact studies indicated above. The risks associated
2. MATERIAL AND SUPPLIER CONSIDERATIONS
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with such a change fall into three main categories: supplier related, material related and the impact to the process (which has been addressed above), see also Figure 4 (26).
An overview of the steps required for supplier qualification and material characterization are provided in Figure 5. Note again that these steps are not necessarily sequential, several can be conducted concurrently.
SUPPLIER QUALIFICATION
MATERIAL CHARACTERIZATION
MONITORING &CONTINUOUS IMPROVEMENT
Supplier PerformanceMonitoring
Supplier Change
Notifications
Supplier Investigations
Supplier Relationship
SupplierAudits
SupplierQuality
Agreements
Supplier Approval
Supplier Status
SpecificationDevelopment
Material Classification
Material Qualification
MaterialCommercialization
Figure 5: Steps in supplier qualification and material characterization
Supplier
• Business Continuity• Quality Systems• Technical Capability
Material
• Safety• Complexity• Handling
Process
• Quality• Performance• Facility Fit
Figure 4: Risk categories for materials for biopharmaceutical raw materials
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SUPPLIER
There are quality, technical and business related requirements for establishing an effective relationship with a supplier. Furthermore, as the use of single-use systems (SUS) increase, which can extend to pre-packed columns, the reliance on supplier quality systems increases. More detailed guidance on the assessment of supplier systems and the use of supplier documentation is available (27,28).
QUALITY
All suppliers must be audited to confirm that an appropriate quality system is in place. This includes change management and notification, management of non-conformances (NCs) and Corrective Action Preventive Action (CAPA) procedures, and extends to their management of sub-suppliers. The willingness of a supplier to share information and demonstrate transparency provides confidence, and is hugely important in assessing impact in change management. A technical diligence assessment is strongly recommended.
TECHNICAL
Suppliers should be assessed on their ability to demonstrate their understanding of their processes, how their products are used and their ability to support an investigation. In particular, details on the resin manufacturing process, critical materials and controls should be shared so that there is a scientific basis to assess any changes the supplier may make to their processes. An emerging capability which should be considered is the supplier’s ability to support data exchange in support of Pharma 4.0, where (amongst many other things) large data sets exchanged between suppliers and manufacturers can be used in support of investigations, genealogy, studies of variability, process modeling and potentially predictive control.
BUSINESS
Although not a quality issue, continuity of supply is a concern of regulators. Due diligence activities should consider e.g. business health and stability, capability to meet capacity requirements, disaster recovery plans, intellectual property/freedom to operate positions and commitment to the biopharmaceutical industry.
MATERIAL
It is important to document the steps taken in material selection and characterization so that the decisions taken by a development team can be reviewed later as part of product lifecycle management. There should also be an assessment of the suitability of the supplier’s specifications, and techniques for the rapid identification of materials (such as IR spectra). The data provided by a supplier in a specification may not be the only data available for ongoing assessment of performance (e.g. suppliers seldom provide information on pore size distribution, which can be indicative of resin performance, but the information may be available on request).
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SAFETY
Certain risks arise from inherent properties of the materials used and from the processes by which they are made. It is therefore necessary to have an understanding of material properties such as toxicity and their potential to cause harm should they happen to be included in the final product, so that appropriate steps can be taken to protect the patient either by detection and removal methods. It is also necessary to have an understanding of manufacturing processes and critical process parameters, to enable an informed assessment of any changes communicated as part of a change management protocol.
Material risks are assessed by subject matter experts with the appropriate expertise, e.g., toxicology, immunology, materials science, mechanical engineering, and environmental health and safety (EH&S). In the case of resins, the required information typically falls into three categories:
• Materials/solvents used in the manufacturing process• Solvents used as preservatives • Leachables from the base matrix (resin) or the ligand
Resin suppliers typically provide Regulatory Support Files, which provide details on raw materials and their sources (as potential leachables), solvents (and their clearance by washing procedures), and leachables studies. The sourcing of materials should be reviewed along with the criteria for qualification of alternative sources. In the example from Genentech (22) the switch was made from a Protein A that had been exposed to both animal- and human -derived materials to an ‘animal-free’ Protein A. Both versions of the Protein A were demonstrated to be comparable, as were the antibodies purified using them (29,30).
The removal of solvents should be reviewed and confirmed by washing studies, in order to comply with expectations (31) and the clearance of in-process leachables should be assessed.
COMPLEXITY
Materials such as resins are complex and may consist of multiple components (e.g., prepacked col-umns). In such cases, it may not be practical to take apart the material for testing, and the user is heavily reliant on the supplier’s quality systems. The license holder is also reliant on the supplier’s quality systems to ensure that the quality of their incoming materials is managed appropriately. Some guidance is provided for materials such as pre-packed columns (28).
PROCESS
The primary concern in changing a resin is its impact to product quality and process performance, which is addressed in Part 1. There can be additional consequences, such as when the capacity of a resin has an impact on ancillary equipment such as buffer tanks, tubing and pump capacity. This could be extensive if a switch to using single-use technology is considered as part of the change protocol.
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CONCLUSION
No single pathway for resin exchange will fit every situation – it will depend on past process experience, the nature of, and motivation for the change, the established conditions for the unit operation and the nature of any additional changes contemplated for the same time. The guidelines above are intended to give directional help to developing a protocol, and in all cases license holders are encouraged to have a dialog with the authorities in their local jurisdiction.
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Brian R. Hubbard, Ph.D. (CMC Bioprocess Consulting LLC)
Brian Hubbard, Ph.D. received his Doctorate in Chemistry from Brown University and completed his Postdoctoral Fellowship jointly at Harvard Medical School and Tufts Medical School. Brian has held a number of leadership positions in the biotechnology industry including senior level positions in Process and Product Development at Genetics Institute, Inc. and Wyeth BioPharma, Inc. (currently Pfizer Inc.). He served as Director of Product Recovery at Immunex Corporation, and Director of Purification Process Development at Amgen, Inc. During his 25 years within major Biopharma Organizations his experience includes process development and regulatory filings supporting greater than 100 clinical stage and 8 commercial products. Brian also served for eight years as head of Technology Development and Innovation for Amgen, Inc. in Purification Process Development and Pilot Plant Operations as Scientific Executive Director. In this role he was responsible for technology development for next generation biomanufacturing technologies for Amgen’s Manufacturing of the Future program. This included Upstream, Harvest, and Downstream technologies including single use systems, flexible manufacturing, and continuous processing technologies. He is currently Chief Executive Officer at CMC Bioprocess Consulting, LLC where he provides consulting services to the Biopharma Industry. Duncan Low, M.A., Ph.D. (Claymore Biopharm LLC)
Duncan Low is a consultant providing technical services in raw materials management and risk management to both manufacturers and suppliers in the biopharmaceutical industry.
He is an active member of several industry groups and scientific advisory boards, including the ASTM, ISPE and PDA. His previous role as a Scientific Executive Director at Amgen (2003 – 2017), where he led the Raw Materials Global Network and Materials Science teams, provided broad insight to materials sourcing and change management. Prior to joining Amgen, he held VP positions at Millipore and Pharmacia Biotech. He has an M.A. in biochemistry from the University of Cambridge and a Ph.D. in microbiology from the University of Glasgow.
DISCLAIMER
The information provided in this document is based on the author’s interpretation of the referenced documents. No claims are made as to the requirements in a specific case and in all cases the reader is advised to refer to the original documents and their possible revisions.
BIOGRAPHIES
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