Use of Legacy Components or Systems for Today's Drug Products
Many manufacturers of new drug products, in particular biologic drug products, use legacy components for packaging, i.e., components they have used over time and with other drug products. This is based on the assumption that packaging components are inert, or that issues can be overcome by reformulation. These legacy components appear to offer the benefits of known performance and supply chain and resultant smooth production with minimal downtime. But legacy components may not meet the quality and regulatory standards of today, which require understanding of potential risks for each individual pairing of drug product and container closure system (CCS). In particular, an understanding of the factors that impact protection, compatibility, safety, and performance, is required.
For example, an ongoing risk to injectable drug products is particles in solution. Particles can result through many ways, such as various incompatibilities, contamination sources like production environment, or insufficient washing. An awareness by drug manufacturers of these issues is essential, particularly knowledge of new options in CCS packaging components, and their ability to mitigate particle issues and help to meet the rigorous quality and regulatory standards of today.
Lack of Innovation Adoption
This pitfall relates to Pitfall-1, although the industry is very interested in innovations, their ability to adopt them is quite slow. The “pain” resultant from non-adoption must be quite visible throughout an organization in order to gain the alignment by all functions needed to drive adoption of an innovation. Of course, there can be major advantages for those who are first movers and are willing to engage in the activities needed for adoption of innovations. This can be greatly promoted through partnerships with the suppliers/owners of a platform or technology. Suppliers can help guide critical product requirements without the drug manufacturer needing to fund a specific development program; suppliers receive useful input from the manufacturers to assure a product will meet industry needs.
One might argue that the barriers to innovation adoption lie in the drug R&D process itself, particularly in the way that scientists and engineers relate to supporting functions such as information technology, intellectual property, legal, procurement/supply chain, operations, regulatory and quality assurance. Ultimately, innovation may be blocked by individuals who cannot exchange information in an understandable way among the various functions, resulting in an inability to convey the importance of the innovation. This challenge, coupled with the frequent lack of clarity as to decision making ownership, and the normal risk aversion due to potential regulatory challenges, is central.
Lack of Awareness: Components May Be Part of a Combination Product
There is an increasing awareness, especially among device engineers and regulatory personnel, on the subject of drug/device combination products, in particular the Quality System regulations specified in 21 CFR 820. The challenge, however, is that historically the industry has been focused on the drug product and package – not the delivery device. Therefore, there was limited understanding of the technical, developmental, and regulatory requirements to meet current combination product best practices, which means combining both the drug and device CGMP regulations. In fact, until the last several years, there was still confusion around the fact that prefilled syringe systems are combination products. This is now noted in several areas on the FDA website and associated combination product guidances. Building this type of awareness takes time.
In some cases, the drug formulation development group is choosing the packaging system – which later may be part of a combination product – even if it begins as a traditional vial system. Quite often reconstitution/transfer systems are used with vials, for example, convenience kits that include a drug product in a vial with a vial adapter. Such a kit is considered a combination product in the North American market. This example highlights that both drug and device CGMPs must be followed from the beginning of the development process. Failure to do so can put many products at risk from the standpoint of regulatory approval.
Failure to Understand Special Challenges of New Molecular Entities
There is a growing complexity to the molecular entities in the industry’s pipeline. Many manufacturers, who had focused on small molecule drug products, are expanding into large molecule biologics, such as monoclonal antibodies (mAbs). mAbs comprise the majority of biologics both in development and already commercialized. This pipeline is becoming more diverse, with the emergence of therapies based upon technologies such as gene, siRNA, oligonucleotides or stem cells. There may be unique needs for these new drug products, and packaging/delivery requirements (sensitivities, storage/delivery) may be quite different from those of small molecules or mAbs. Thus, it is essential that the starting point for all packaging be the needs of the molecular entity – to ensure suitability and ultimately safe delivery to the patient.
Fran L. DeGrazio is Vice President of Scientific Affairs and Technical Services at West Pharmaceutical Services, Inc. She has been in the pharmaceutical packaging industry for over 30 years with extensive expertise in the area of delivery of injectable drug products, such as vial/closure combinations, prefillable syringe systems and injectable combination products. In her current role, she is focused on providing scientific industry leadership and innovation around West’s new products and services.