GMP BUFFER MANUFACTURING

What are buffers?

 

Buffer manufacturing involves the mixing of either weak acids and their conjugate bases or weak bases and their conjugate acids. Aqueous solutions of such mixtures resist changes in acidity or basicity of a solution, or pH, relative to other components. Biological buffers maintain pH of a biological system at a near constant level, even when there is change in the hydrogen [H+] ions or hydronium ions [OH-] in the system. Acids donate protons whereas bases accept them. Thus, by accepting and donating additional electrons and protons, buffers maintain overall pH at a near constant level.

 

How are buffers employed in the biopharmaceutical industry?

 

The role of buffers in upstream and downstream biologics processing

 

Commercial manufacturing of protein-based biologics includes several complex steps which require different buffers for pH stabilization and control of processes. During upstream biologics processing, buffers such as HEPES are mainly used to help maintain pH of culture media within a specified range, to achieve conditions necessary for cell growth. Stabilized pH enhances production of desired proteins whilst maintaining the protein’s structural and functional integrities before downstream processes begin.

 

During downstream biologics processing, buffers are used to maintain specified purification parameters as well as the ionization state of biological material for optimal chromatographic purification. Buffers are crucial in maintaining structural and functional integrities of proteins during harsh downstream conditions. Some of the widely used buffers in downstream biologics processing are GMP grades of MES, TRIS, Guanidine Hydrochloride, Ammonium sulfate and citrate buffers.

 

The role of buffers in biologics formulations

 

Buffers are as important in manufacturing processes as they are in formulations. Maintaining required pH range in the final formulation is essential to ensure biologic drug stability across varying storage conditions over the entire clinical or commercial shelf life of the final formulation. Buffer manufacturing for end products involves careful selection of ingredients, to achieve specified buffering range to stabilize the final formulation. Since buffers used in biologics formulation manufacturing come in direct contact with the therapeutic agents, GMP grade buffers are critical to ensure safety and efficacy of the final formulation. Some of the widely used buffers in formulations include GMP grades of citrate and phosphate buffers.

 

Why GMP grade buffers?

 

Buffer manufacturing carried out under full GMP compliance is necessary to meet or exceed compendial purity standards. GMP grade buffer manufacturing is highly sought after by biopharmaceutical companies involved in the manufacturing of complex biologics. GMP grade buffer manufacturing ensures full compendial testing compliance, traceability, consistency and transparency in supply chain and adherence to GMP and GDP practices as laid out by compendia such as USP, EP, BP and JP. Early stage, late stage and commercial biologics products require GMP buffer manufacturing to meet the safety and efficacy standards required by the target markets for which the products are developed and manufactured. GMP grade buffers are also widely used as vaccine excipients and in the manufacturing of novel Gene Therapy.

 

Why is custom GMP buffer manufacturing required?

 

Every biological process requires a unique range of pH tolerance and to achieve this, custom GMP buffer manufacturing is crucial. Although some standard buffer solutions containing MES, TRIS HEPES and phosphates can be used, custom GMP buffer manufacturing is recommended, especially for developing novel processes and formulations.

 

Custom GMP buffer manufacturing serves the requirements of process-specific buffers having specified pH range manufactured under full GMP compliance. Buffer manufacturing conforming to compendial requirements is essential in the development and manufacturing of novel therapeutics.

 

Why is GMP buffer manufacturing outsourced?

 

As mentioned on our dedicated buffer manufacturing page, GMP grade buffer manufacturing requires dedicated equipment, personnel and facilities, preferably in close proximity to the end user to control transportation and regulatory costs. For these reasons, GMP buffer manufacturing often creates bottlenecks and supply delays at the end user’s manufacturing facility, creating an increasing need in outsourcing such activity. At A&C, we provide cost effective, flexible and tailored solutions for your buffer outsourcing and cleaning solution needs, including localized manufacturing and safety stock availability. Our GMP manufacturing plants are ISO 9001:2015 certified and our buffers can be manufactured with WFI (Water for Injection) or USP water.

 

Glossary:

 

GMP – Good Manufacturing Practice

TRIS – Tromethamine Hydrochloride

MES – 4-Morpholineethanesulfonic acid monohydrate

HEPES – 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid

USP – United States Pharmacopeia

EP – European Pharmacopoeia

BP – British Pharmacopoeia

JP – Japanese Pharmacopoeia

 

 

 

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