Buffer preparation is one of the most crucial processes in the biopharmaceutical industry. However, buffer production is an expensive, time-consuming, and labor-intensive process that requires significant floor space and specialized equipment. Additionally, buffer storage during the large-scale production of biopharmaceuticals can be a challenge as buffer storage requires a large floor space at a time when emerging product classes are driving the need for multi-use, multi-scale manufacturing. To overcome the challenges associated with conventional buffer preparation / buffer manufacturing processes, pharmaceutical players are either installing novel buffer preparation systems in their manufacturing facilities or outsourcing buffer manufacturing needs to third party service providers. The global buffer preparation systems market is anticipated to grow at a CAGR of around 5.9%, till 2035. Driven by the growing demand for buffers and challenges associated with buffer manufacturing, the buffer preparation systems market is anticipated to witness steady growth in the coming decade.
Conventional Methods of Buffer Manufacturing
A buffer solution is a mixture of weak acids and their salts or a mixture of weak alkalis and their salts. The various steps involved in conventional buffer manufacturing process have been described below:
- The buffer preparation process starts with mixing acid / alkali with an aqueous solution of salt while measuring the pH of the solution with pH meter. The solutions are mixed until a buffer of a desired concentration is achieved.
- The mixed solution from the bag or carboy is then transferred to the bioreactor using a pump or gravity. Single-use instruments, including flow sensor, pH sensor and pressure sensors, are used to ensure the production of quality buffers.
Novel Methods of Buffer Manufacturing
In order to address the aforementioned challenges associated with buffer preparation and buffer storage, several players have developed novel buffer preparation systems / in-line conditioning systems which enable simultaneous preparation of buffer from raw materials and their use in upstream and downstream applications. Integrated with automated technology platforms and sensors, such systems have allowed precise and controlled production of buffers in a timebound manner. It is worth highlighting that the use of novel buffer preparation systems / inline buffer conditioning systems has already demonstrated promising results in buffer manufacturing, in terms of process automation, time reduction and buffer quality. Various components of the novel buffer manufacturing systems have been explained below:
- Single-use Technology: Single-use equipment enables faster preparation of downstream buffers, which may then be used directly in the biomanufacturing process, while eliminating any post-preparation challenges associated with the conventional system. In addition, adoption of these techniques enables reduction in footprint and lower the capital costs associated with buffer preparation. This can be attributed to the fact that these disposable systems usually do not require steam-in-place or clean-in-place utilities, unlike conventional systems.
- Inline Conditioning: Inline conditioning is a process that enables on-the-spot buffer formulation which can be directly integrated with the various steps of downstream processing. In this process, various buffer components like water for injection (WFI), salt and concentrated buffer stock solutions of the necessary acids or bases are used to formulate buffers. Several pump line5s are used for mixing acids, bases and salts. Inline conditioning allows dynamic control of pumps and provides more flexibility to the user.
- Inline Buffer Dilution: Inline buffer dilution is a process of buffer preparation from a concentrated buffer solution for on-demand purposes at the point of use. It offers several advantages over conventional buffer manufacturing procedures, including fully automated buffer preparation process, full control on flow rates, temperature, and pH, and is highly adaptable and agile procedure to ensure that predefined setpoints are met, even if they differ from one process to the other. Additionally, for inline buffer dilution, buffers are supplied in single-use containers, which reduces the footprint and, therefore, is one of most efficient
Advantages of Outsourcing Buffer Manufacturing
Given the technical and operational challenges associated with the production of buffers, innovators in the biopharmaceutical industry are increasingly relying on the contract service providers for their buffer manufacturing needs. Some of the primary advantages of outsourcing operations related to buffer manufacturing are briefly described below:
- Cost savings: Companies that partner with third-party service providers need not invest in establishing new facilities for buffer preparation or maintain a qualified workforce that can carry out analytical testing of buffer products. Several companies outsource their business processes to companies situated in developing countries with low labor costs. Additional cost benefits are derived from economies of scale.
- Access to advanced capabilities and technologies: Partnering with third-party service providers grants customers access to manufacturing capabilities and technology platforms that they would otherwise have to procure at very high costs.
- Flexibility: It is one of the key reasons for outsourcing for many companies. The contracts of outsourcers as well as the jobs of employees directly depend on the degree of flexibility to reflect changes in the business environment.
- Risk Sharing: One of the crucial factors determining the net outcome of any industrial process is risk analysis. Outsourcing a few components of the overall industrial process of developing and manufacturing buffers enables shifting certain responsibilities to the outsourced vendor. Henceforth, there is a mutual understanding between the companies to handle the risk factors in a better way.
Key Considerations While Selecting An Outsourcing Partner
Buffer preparation is a multi-step process and selecting a suitable service provider for outsourcing different operations is one of the challenges for drug developers. Despite the several cost benefits and technical expertise, there are other parameters that need to be considered while selecting a service provider. Some of the key parameters that can be considered to assess the expertise and capabilities of third-party service providers have been briefly described below:
- Protection of Intellectual Property: In order to protect intellectual assets of the developer in the country in which the third-party service provider is based, it is important that the country have proper provision for protection of intellectual property of the drug developers.
- Operational capabilities: Presently, pharmaceutical companies are interested in service providers that, if required, implement improvements in the pre-decided buffer formulation. It is important to figure out if the prospective third-party service providers have the capability to integrate themselves within various components of the value chain and serve as a one-stop-shop service provider.
- Quality management: Quality assurance is one of the most important and critical parameters that a pharmaceutical company needs to evaluate before handing over a project to a third-party manufacturer. This includes a range of responsibilities, such as the ability to produce buffers that are aligned with cGMP practices.
- Location: The proximity of the third-party service provider partner is an important factor to consider when selecting a third-party service provider. This becomes especially important in projects where technical complexities require the client company to conduct frequent visits to the production or processing site.
- Offshoring operations: While outsourcing operations to a third-party service provider based in another country, various challenges may arise, such as barriers related to language and a different time zone.
- Previous track record: The past performance of a third-party service provider on similar projects is an important factor while contracting its services. Hence, references from previous work experience with companies of comparable size can provide important insights that may be used to evaluate the reputation and reliability of the company.
- Other key parameters: Some of the key variables that are considered by pharmaceutical companies while selecting a suitable third-party service provider include technical expertise, efficiency, appropriate infrastructure and the ability to meet pre-determined timelines. The extent of service offerings and the amount of involvement of a third-party service provider are usually dependent upon the developer company.
The growing demand for buffers and challenges associated with buffer manufacturing has prompted various pharmaceutical companies to leverage the expertise of players offering novel buffer manufacturing systems and related services. It is worth highlighting that novel buffer manufacturing systems are integrated with a wide range of features, including conductivity sensors, pressure sensors, temperature sensors, pH sensors and filters. Notably, a large number of buffer manufacturing systems have been developed to operate in an automated mode, reducing the risk of errors prone to human interface. In addition, over 20% of the buffer manufacturing systems offer preparation of both diluted and conditioned buffers, offering flexibility to users. Driven by the growing demand for buffers, and ongoing efforts of buffer manufacturing service providers, the market is anticipated to witness steady growth in the coming decade.
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