Process filtration solutions for safer and efficient API manufacturing

Active pharmaceutical ingredient (API) production is a cornerstone of pharmaceutical manufacturing, representing a global market valued at approximately USD 250 billion. The process involves the storage, transfer, and controlled addition of ingredients and excipients, often including harsh solvents and acids, for drug substance manufacturing, followed by formulation and filling. Contamination during API manufacturing can significantly reduce yields, jeopardize regulatory compliance, and compromise both product quality and patient safety.

At Atlas Copco, we support pharmaceutical manufacturers in reducing contamination risks in API production through robust process filtration solutions. This page outlines the key contamination risks in API processes and highlights reliable filtration solutions that help maintain efficient production and ensure safe, high-quality products.

API manufacturing involves the integration of many input materials, solvents, and intermediates, many of which can introduce contaminants, such as microbial or particulate matter, into production lines. Storing these ingredients can create opportunities for contamination through venting systems, while plant personnel are a source of both particulate and microbial contaminants. Equipment corrosion and wear, as well as the aggregation of components during processing, can also produce contaminating particles. The sources of these contaminants and their potential effects on API production and product quality are discussed in more detail below.

Starting Active Materials for Synthesis (SAMS), the precursors used in API production, can be a potential source of microbial contamination. While many SAMS are chemicals and solvents that do not readily support microbial growth, others, such as plant extracts, may carry contaminants. Contamination can also occur throughout the supply chain, depending on container quality and exposure to environmental conditions that introduce moisture and promote microbial growth. During production, microbial ingress can occur through storage tank venting systems, water systems, and plant personnel. Such contamination can have serious consequences for product quality and patient safety.

Particulate contamination can arise from a range of sources during API production and subsequent manufacturing processes. Particles may enter facilities through raw materials and liquids, including water, and may consist of plastics, metal fragments from container debris, or ingredient aggregates. Additional particulates can be introduced during production by plant personnel and can include skin flakes, hair, and fibres from garments. If not removed early in the process, particulate contamination can damage sensitive downstream equipment, disrupt production, and create regulatory compliance risks. Should these contaminants reach the final product, they may also compromise patient safety.

Process filtration is essential for removing a wide range of contaminants throughout API manufacturing. Process filtration can be applied at several stages, including when raw materials enter the production line, before, during, and after storage, prior to reactor processing, during formulation, and before final filling. Key process filtration steps used in API processes are outlined below.

• Prefiltration: This process filtration step can be applied when transferring materials to and from storage to ensure that liquids, such as water, solvents, and ingredient solutions, are free of particles before entering reactors or formulation processes. It also helps to protect more sensitive filtration processes such as sterilization filtration. Atlas Copco provides PFP⁺, PFP⁺ A, and PFP⁺ D polypropylene (PP) filters for prefiltration and bioburden reduction across a range of liquid types.
  
  
• Sterilizing filtration: This process filtration step is crucial as a safeguard against microbial contamination in API production processes. Key stages for implementing sterilizing filtration include venting on storage containers and formulation equipment, as well as immediately before formulations enter the filling line. Atlas Copco provides SMT-G polytetrafluoroethylene (PTFE) filters for venting and SME⁺ polyethersulfone (PES) filters for formulations prior to filling.