Many regenerative medicine products represent a convergence of pharmaceutical, biologic, and medical device technologies. Although such products could have a great impact on medicine, they often pose significant challenges for their developers, requiring companies to incorporate competencies from several technology sectors. By addressing commercial regulatory and manufacturing challenges at an early stage in product development, these companies are more likely to succeed in reaching their commercial goals.
Exact regulations governing the manufacture of a convergent technology — or “combination product” — such as a biologic and delivery device depend on the primary designation applied to that product by regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Different regulatory agencies have different requirements, so companies must establish manufacturing processes that comply with the strictest regulations for which they intend to seek approval.
A Few Examples
The Dermagraft bioengineered skin substitute, for example, consists of human fibroblast cells embedded in a bioabsorbable mesh for the treatment of diabetic foot ulcers. It is regulated by the FDA as a medical device, reimbursed by the Centers for Medicare and Medicaid Services as a biologic, and would be regulated by the EMEA as an advanced therapy medicinal product. The product’s manufacturer must adhere to all applicable device and biologic standards and regulations. Doing so can pose a challenge, especially when companies try to define what requirements are applicable.
Another example is the INFUSE bone graft, which consists of a recombinant version of a naturally occurring protein (BMP-2) that is combined with a collagen-based carrier for delivery. It is approved for use in multiple indications including spine fusion, treatment of open tibia fractures, and certain oral and maxillofacial applications. Although BMP-2 is a protein biologic, combining it with a collagen sponge requires regulation as a medical device.
Drug-eluting stents are a type of device–drug combination that has had a profound impact on the practice of medicine. Regulated as medical devices, they provide an immediate mechanical benefit through placement of a stent to help keep coronary arteries open following an angioplasty procedure. The drug component that’s coated onto the stent helps prevent restenosis from occurring in the months following such a procedure.
Do Your Homework
To fulfill conflicting requirements on such complex products, development companies must not only comply with regulations governing safety and efficacy, but also the vast array of regulations covering product manufacturing, packaging, facility validation, consistency and safety of materials, sterility of the product, and (where appropriate) sterilization and viral inactivation procedures.
Regulatory requirements for manufacturing can vary greatly among international regulatory agencies. As such, guidelines that meet one agency’s requirements may be insufficient for another’s. Thus, it is essential to cultivate an early understanding of the regulatory requirements for all potential markets in which a product may be sold. Because the regulatory environment is ever changing and requirements are increasingly stringent, it is critical for combination product manufacturers to continuously assess their manufacturing processes and accreditations to ensure that they remain in compliance with current regulations.
To demonstrate compliance with different regulatory agencies, companies should seek certifications and accreditations relevant to their products’ specific technology categorization and within specific geographies. For example, a company with a medical device product for the EMEA market may seek ISO 13485 certification, a quality-management standard for medical device manufacturing as established by the International Organization for Standardization. Similarly, a US company with a cellular therapeutic product may apply for accreditation by the American Association of Tissue Banks (AATB), affirming that the company’s product manufacturing meets or exceeds all AATB safety standards with regards to handling, processing, labeling, packaging, storage, and distribution of tissue.
A thorough understanding of the manufacturing and regulatory guidelines and requirements for development of convergent technologies will help ensure a company’s success in meeting the challenges it will face in bringing new products to market.
Kathy McGee is vice president and general manager, and Andrea Loewen-Rodriguez is executive director for regulatory affairs at Advanced BioHealing, Inc., 36 Church Lane, Westport, CT 06880; 1-858-754-3700.