Single-use technologies reduce manufacturing time and costs by eliminating cleaning and validation steps. Along with these benefits, however, come new considerations including chemical compatibility of plastic components and the shift of critical validation strategies from the end-user to the supplier.
More stringent validation requirements and increased use of Quality by Design (QbD) and Process Analytical Technologies (PAT) demand greater scrutiny of sampling processes. Traditional sampling methods do not meet the expectations of regulatory authorities, due to the risk of contamination through open ports in the manufacturing system and the potential for operator error.
Implementing an optimized sampling process reduces risk and increases productivity. An effective sterile sampling system can reduce the potential for contamination, using good sampling practices to monitor filter effectiveness and assess process and product quality.
Single-use equipment is typically manufactured from polymeric materials. Process fluids, depending on their chemical composition, might negatively interact with these polymers. The challenge is finding materials of construction which are compatible with the manufacturer’s raw materials and process streams. Moreover, it is often difficult to find detailed guidance on the steps needed to demonstrate chemical compatibility. Regulatory and guidance documents cover a wide variety of products and processes and do not provide detail on specific methods or procedures.
Proper selection and qualification of single-use equipment and materials for pharmaceutical manufacturing should include a thorough assessment of the chemical compatibility of the product contact components. It is important to partner with a supplier who:
The implementation of single-use technologies in the final filling process is steadily increasing. Single-use technologies need to meet the stringent requirements for this final process step – fluid path sterility, integrity, operational safety, and fit for purpose of the single-use assembly. New single-use final fill solutions can effectively meet these requirements with proper assembly design for integration in a filling machine. Evaluation of risks and regulatory compliance are among the key design considerations for a sterile filtration process, making it essential to evaluate supporting documentation to enable appropriate validation.
Drug manufacturers face pressure to efficiently and effectively advance pipeline assets while minimizing risks associated with product loss, product contamination, sterility, and patient safety. Single-use fill-finish assemblies can improve filling line productivity – providing flexibility to manufacture a variety of drug products and fill volumes while mitigating contamination risks. However, managing implementation and regulatory risks can be a challenge with single-use fill-finish assemblies, requiring rigorous process validation to ensure compliance with regulatory guidelines. Steps which can be taken to ensure this validation are:
Overcoming increasingly complex obstacles in small molecule drug manufacturing requires a strategic approach to processing, formulation, regulatory compliance, raw material quality, and supplier selection
Sterile liquid applications are often injected into the body, making it critical to minimize risk by choosing the right process to purify the API, identifying suitable excipients, defining appropriate process validation, and selecting the right filters.
Typical solid dose challenges include API solubility and final formulation API stability, controlling total cost of manufacturing, and creating a robust, homogeneous tablet free of complications during packaging or storage.
Drug products must be free from bacteria and other microorganisms to ensure patient safety, requiring expert use of aseptic filtration for pharmaceutical products that cannot be terminally sterilized.