Pursuant to the proposal for validated minimum standards for biopharmaceutical contract manufacturing organization (CMO) request-for-information (RFI) and request-for-proposal (RFP) processes (biopharmaceutical vendor evaluation and selection minimum standards, BioVesel) (1), we propose herein a multistep research protocol to develop and implement the BioVesel standards. This proposal is intended as a basis for discussion among mulitple stakeholders. Detailed research protocols for each proposed stage in the development and implementation of BioVesel will be drafted and published separately. The context of the proposed research is an exercise to gather and synthesize the opinions of stakeholders involved in the evaluation, acquisition, provision, and oversight of biopharmaceutical CMO services (Table 1).
Table 1 shows the many stakeholders engaged in a contract manufacturing lifecycle (evaluation, acquisition, provision, and oversight). You might be surprised by the breadth of stakeholder participation in the CMO lifecycle and reflect on your past experiences of CMO RFI/RFP processes in which a significant
number of those stakeholders may have been omitted a priori (2). In particular, the early engagement of CMO and biopharmaceutical company board of directors (BoD) members often is omitted from CMO tendering and management processes. BoD member engagement often is restricted to approval for management to enter into a master service agreement (MSA) with a CMO and in the event that something unfortunately goes wrong (3).
Proactive biotechnology corporate governance is essential at all stages of company and vendor contract lifecycles (1, 4). For example, biopharmaceutical company BoD members should be actively engaged in high-level evaluation, development, and implementation of RFP processes. That includes regular updates from management to ensure that managers have clear direction from directors and/or shareholders (5).
Such actions also will reduce the risk of BoD members — particularly those with a limited biotechnology background — of feeling “blindsided” by the process and experiencing “sticker shock” when asked by management to approve a final MSA and/or statement of work (SoW) (6). We suggest that CMOs communicate clearly with their internal executive management and BoD members as necessary to ensure clarity on resource and investment implications associated with new clients and contracts (7). Industry veterans unfortunately are hardened to stories in which CMOs enter into contracts they are subsequently unable to fulfill.
The scope of the protocol for BioVesel development is restricted to procurement of services according to the production of good laboratory practice (GLP) or good manufacturing practice (GMP) active pharmaceutical ingredient (API), which includes process development activities. Assay development, immunogenicity, external API and ancillary product testing, and standalone installation/operational/performance qualification (IQ/OQ/PQ) services are beyond the intended scope of BioVesel (8). BioVesel will apply to services in most jurisdictions and for procurement of services with a contract value that is of material risk to a tenderer (which naturally will vary by company size and development stage).
BioVesel objectives will be updated continuously based on interstakeholder feedback (9). We propose 19 potential objectives (see box, next page) for the BioVesel standard as a basis for discussion. They pertain to the BioVesel standard itself rather than to RFP processes that implement the BioVesel standard.
BioVesel Standard: Research, Development, and Implementation
Research, development, and implementation of the BioVesel standard will be driven by interstakeholders’ needs to maximize end-user utility and adoption (10). We are committed to ensuring that all aspects of the standard are grounded in robust research methods.
We propose the following key aspects and methods of a multistep research protocol to develop and implement the standard for the development and implementation of BioVesel:
- Systematic review of RFI and RFP processes and standards with specific reference to healthcare
- Meta-analysis and systematic review of RFI and RFP processes and standards stratifying between pharma and nonpharma
- Semistructured interviews with exemplar stakeholders (Table 1) to determine potential stages and documentation in RFP processes
- Delphi study of draft BioVesel RFP processes and templates
- Pilot study using draft BioVesel RFP processes and templates
- Meta-analysis of end-user feedback of draft BioVesel RFP processes and templates
- Evaluation study deploying updated draft BioVesel RFP processes and templates
- Meta-analysis of end-user feedback of updated draft BioVesel RFP processes and templates
- Update and issue of V1.0 BioVesel RFP processes and templates
- Implementation of processes for continuous review and revision of processes and templates
- Implementation of BioVesel audit process through a recognized independent third party (e.g., notified body).
Clarity, Competition, and Completion
The BioVesel objective and concept remain crystalline: Provide a simple, adaptable, and transparent framework for CMO service procurement and delivery. However, the route to implementation is complex. In particular, we highlight the need for BioVesel to prompt and support resource requirement planning within CMOs, supported with communication with their senior management and BoD members. That is a multiparty challenge that requires a multiparty solution.
Reflecting on the methods proposed here and in discussions with potential standard codevelopers and adopters, we highlight the criticality of three “watchwords” set forth in the BioVesel context, scope, and objectives: the need for clarity, competition, and completion. This trinity encapsulates neatly the three main failure modes of current relationships between CMOs and biopharmaceutical sponsor companies. We hope that through BioVesel, these three areas can represent heuristics for success. Currently, although the biotechnology industry develops and evolves at the speed of a bullet, some of the supportive framework is moving at the pace of a mammoth. Now is the moment to catapult our efforts into the 21st century, with standards fit-for-purpose to ensure that our businesses do not go extinct.
|Potential Objectives for the BioVesel Standard|
|Transparency: All aspects of the standard must be transparent among all stakeholders, including processes for development, implementation, and revision of the standard.|
|Integrity and Traceability: The standard shall be subject to clear and appropriate controls in regard to issue, revision, and validation.|
|Enforceability: Efforts shall be made to adopt the standard incrementally on a communitywide voluntary basis.|
|Adaptability: Processes and procedures shall be developed for adaption of BioVesel to accommodate short-term nuances of specific RFP processes or technologies and long-term technological and business environment changes.|
|Use of Existing Best Practices: BioVesel shall seek to learn from and implement existing best practices from within and outside the biopharmaceutical space, including ISO standards and other standards set forth by professional and/or trade organizations.|
|Framework for negotiation processes shall be defined to support the management of interstakeholder expectations and standardization of all aspects of the RFP process, subject to overarching legal or regulatory requirements.|
|Framework for Resolution of Conflicts: Frameworks for negotiation processes shall be defined to support the management of interstakeholder expectations and standardization of all aspects of the RFP process. This will be subject to overarching legal or regulatory requirements.|
|Vendor Validation/Prequalification: Vendors shall undergo a (pre)qualification process before participating in RFP processes.|
|Tenderer Validation/Prequalification: Tenderers shall undergo a (pre)qualification process before participating in RFP processes.|
|Clearly Define Documentation Required: Any and all mandatory documentation required during the procurement process shall be defined in advance.
|Clearly Defined Parties and Their Respective Roles: The roles and responsibilities of all parties participating in RFP processes shall be defined in advance of the process commencing and updated throughout as required.
|Transferability: Insofar as possible, BioVesel shall be applicable and transferable to the maximum range of technologies, vendors, tenderers, and jurisdictions.
|Auditable: Alignment with the standard must be auditable by first-, second-, and third-party auditors.
|Permit Comparison and Contrast of Potential Service Providers/Vendors: The standard shall propose data and tools that should be collected and applied to support comparison and contrast of potential service providers and vendors by clients.
|Permit Comparison and Contrast of Potential Clients: The standard shall propose data and tools that should be collected and applied to support comparison and contrast of potential clients by service providers/vendors.
|Encourage Competition: BioVesel shall encourage and promote competition among service providers and potential clients.
|Encourage Completion: BioVesel shall encourage and promote completion and delivery of mutual commitments among service providers and potential clients.
|Risk Identification and Management: The standard shall proactively seek to identify and manage stakeholder risks on a continuous basis.
|Minimize Risk of Effort Duplication: All efforts will be made to ensure that the development, implementation, and revision of the standard shall not impart significant additional burdens on stakeholders. In particular, it should prevent duplication of effort and processes.
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Alison R. Carter is a research fellow, Edward Meinert is Sir David Cooksey research fellow, and David A. Brindley is senior research fellow in Healthcare Translation and group lead at the University of Oxford, Healthcare Translation Research Group, Department of Paediatrics, Oxford, UK; corresponding authors: firstname.lastname@example.org and email@example.com.