In your opinion what are the most important properties raw materials/functional excipients can give to finished pharmaceutical products? Why?
Bikash Chatterjee, President and Chief Science Officer, Pharmatech Associates: The contribution of functional excipients has greatly increased over the last decade. The key impacts made by functional excipients in finished products include solubility and range in some cases from drug efficacy to masking taste and extending product shelf life.
Susan Burke, PhD, Director Process Development – Materials Science; Jackie Milne, PhD, Principal Scientist; Ron Kelly, PhD, Principal Scientist; Ting Wang, PhD, Senior Engineer; Patrick Gammell, PhD, Executive Director Process Development, Amgen: Amgen is an attribute led, patient-centric organization. We design for the patient; therefore, our excipients are important for ensuring we can to deliver to our target product profile. Excipients serve many important roles in the production of finished pharmaceutical products. They are selected for the specific functionality they afford to the formulation such as providing the right osmolality or protection of the therapeutic molecule from shear stresses. The excipients must be inert to avoid impact to the stability and the pharmaceutical profile appropriate for the intended use of the finished drug product. In addition, compendial compliance ensures that the excipients meet the quality standards for use in pharmaceutical products. Consistent performance and quality of the excipients is important for optimal efficacy at the time of administration of the finished drug product. Adhering to those standards supports our ability to delivery patientcentric products to the market.
As the pharmaceutical market moves toward more specialized treatments, what benefits can raw materials and functional excipients provide to these new types of drugs?
Chatterjee: One area of innovation we see now involves excipients that are co-processed as part of the API manufacturing process, resulting in API formulations that can be more easily manufactured. One significant area where the impact of functional excipients is seen is in biologic drug and vaccine development. Biologics are susceptible to degradation from both storage and processing conditions. Newer functional excipients can stabilize these products that are prone to destabilization from a variety of mechanisms.
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Burke, Milne, Kelly, Wang, Gamell: Raw materials, both noncompendial and compendial excipients, will continue serve as enablers for ensuring stability and delivery of therapies for patients, as these components are essential for the development of such products. However, for novel non-compendial materials, a paradigm change is required to be able to meet the needs of specialized medicines. A shift to a more attribute-focused approach for materials is warranted. Like the Quality Target Product Profile (QTPP), a Material Target Attribute Profile (MTAP) can serve as a framework for capturing information on raw material performance requirements, relevant material attributes, impact on process and product performance, target attribute ranges, and control strategies. This approach provides a better understanding of the influence of raw material variation for enhanced reliability in manufacturing and product quality. An attribute-centric approach to raw materials ensures that the attributes important for the development of specialized medicines are identified and controlled, which will support patient-centric outcomes.
What are some important attributes a supplier of raw materials/functional ingredients must have in order to meet the product demands of the marketplace?
Mark Mitchell, Principal Engineer, Pharmatech Associates: As the pharmaceutical industry embraces Quality by Design, a key element of process understanding is how raw material variability impacts drug product quality. Providing a raw material that simply “meets spec” is not sufficient in this new paradigm. A supplier should have intimate knowledge of their product (i.e., raw material/functional ingredient) in terms of its process control and capability relative to its quality attributes. By providing this data to drug product manufacturers during product design and development, the criticality of that raw material/functional excipient to finished drug product can be appropriately evaluated by either design of experiments or risk assessment. Knowledge of raw material variability when moving from small-scale to commercial scale processes allows for more predictable drug quality as product quality issues due to unexpected changes in raw materials can be avoided.
Burke, Milne, Kelly, Wang, Gamell: To keep pace with the increasing demands of the pharmaceutical industry, raw material suppliers must place emphasis on ensuring they develop strong partnerships with pharmaceutical manufacturers and actively engage in seeking the voice of customer. It is imperative they understand the requirements for raw materials to be used in a regulated environment. To deliver on the needs of the pharmaceutical industry, suppliers must have a strong quality management system and a philosophy of transparency as their foundation. It has become increasingly important for suppliers to implement robust monitoring programs including statistical process control strategies and the capability to readily transfer raw material data to their customers. This must be supported by depth and breadth of technical knowledge, testing capabilities, and engagement with their supply chain partners.
As the globalization of the pharmaceutical industry continues – what must ingredient suppliers do to ensure the quality of their products and the availability of same?
Chatterjee: Over the last decade the emerging markets in particular have stumbled badly in terms of ensuring excipient purity, consistency, and functionality. To be competitive, investing in process understanding will become essential, especially as the complexity and sophistication of new drug delivery forms continues to escalate.
Burke, Milne, Kelly, Wang, Gamell: Supply-chain transparency is of vital importance in an age of increasing globalization. The parties representing each link of the supply chain need to be open and appreciative of their roles. A pharmaceutical company must be knowledgeable about their raw material supply with traceability throughout each level of supply chain, as far as is necessary. This is critical to both ensuring supply continuity in the event of a local disaster and supply-chain integrity in the event of a deliberate attempt at adulteration.
Transparency leads to increased predictability. Information about changes introduced to a material allow for an understanding of the primary sources of variation, thus enabling us to predict the outcome of pharmaceutical manufacturing. Communicating such changes clearly allows for better understanding and control over potential downstream impacts.
The pharmaceutical industry is adopting best practices, such as developing robust supplier-relationship and detailed technical engagement, to enhance raw materials reliability. Another important element for advancing knowledge of raw materials is the transfer and analysis of suppliers’ data. A standard guide for electronic data transfer (ASTM E-3077-17) from supplier to pharmaceutical manufacturers has been established in 2017. Data analytics can facilitate enhanced engagement between the pharmaceutical industry and suppliers, through the sharing of the analysis to suppliers for mutual learning and improvement. The enhanced collaboration requires improved standardization in key areas such as terminology, units, SKUs etc.
Looking at the future, what role will suppliers of raw materials/functional ingredient have as drug development becomes more complex and more specialized?
Chatterjee: We will see more drug development companies looking to partner with key functional excipient suppliers to produce consistent and ready-to-process APIs. Continuous manufacturing itself is hugely API dependent and demands a steady and reproducible product to realize the long-term benefits of such new innovative approaches to drug production.
Burke, Milne, Kelly, Wang, Gamell: As drug development continues to evolve, so too must the relationship with raw material suppliers. Strong partnerships built on trust and a commitment to transparent communication are a must for keeping pace with advancements in the pharmaceutical industry. With the globalization of supply chains and increasing complex distribution channels throughout the world, raw material suppliers must enhance the resilience of their organizations by building robust business continuity strategies that take into consideration the potential for unforeseen challenges such as natural disasters. In addition, suppliers must continue to strengthen their supply chains, control strategies, and reliability of their materials. The increased complexity of drug development a deep understanding of raw material variation is of great importance. Suppliers that employ advanced data analytics to monitor their material attributes, in combination with robust process control strategies, will be well equipped to support their customers in the pharmaceutical industry.