When working on topical generic products, dealing with regulatory bodies like the US Food and Drug Administration, European Medicines Agency (EMA), and other can be challenging for pharmaceutical companies and their contract development and manufacturing organization (CDMO) partners. For example, there’s an increasing emphasis on matching the physical structure/microstructure, which can be tricky.
Lynn Allen, vice president of business development in North America for MedPharm, discussed the finer points of topical generics with Outsourcing-Pharma, including how regulatory requirements and guidance have evolved over time.
OSP: How has the generics market evolved in recent years?
LA: The Generic Drug User Fee Amendments (GDUFA) authorization in 2012 increased the interest and number of generic development programs. Since that time, multiple submissions have led to changes in the landscape of product development and their projected investment returns.
In 2020, the FDA approved the lowest number of products than in the previous four years. The crowded field for one generic product has created ROI challenges. Consequently, generic companies have become more strategic with their product portfolios.
Development of more complex dosage forms that are more challenging to formulate can lead to a less crowded market environment. Complex topical dosage forms are an example of this new market trend.
OSP: Then, please tell us a bit about the topicals field—what challenges do these products encounter that pharma products in other areas don’t?
LA: The number of excipients in a topical product can be high with each excipient having an impact on the formulation’s bioavailability, penetration, dose homogeneity, and stability. Expanding the complexity of formulation development is the multiple grades of each excipient which can impart slightly different characteristics making deformulation and formulation development exponentially difficult than the development of an injectable or a solid oral dosage form.
OSP: Could you please tell us how the ways regulations impacting topical bioequivalents have changed over the years?
LA: The FDA and EMA have been increasing their focus on matching the physical structure/microstructure of the reference product which involves extensive rheological characterization and a potential assessment of drug in solution and suspension over shelf life. In addition, comparison of the metamorphosis or transformation of the products upon application is becoming mandatory.
Depending upon the complexity of the topical reference product, the use of validated IVRT and IVPT methods either individually or in combination are then required to demonstrate bioequivalence between the reference and generic products
OSP: In what ways do you think regulatory agencies like the FDA and EMA might change their approaches and requirements, in order to make things as easy and effective as possible (without undue risk to patient safety)?
LA: The FDA and EMA have initiatives to allow for bioequivalence testing in lieu of costly clinical trials to prove equivalence to the RLD (Reference Listed Drug). MedPharm has experience with bioequivalence testing for topical programs and can help navigate through the challenges of this work.
On August 18-20, the FDA will actually be co-hosting a free virtual public workshop with the Center for Research on Complex Generics titled In Vitro Release Test (IVRT) and In Vitro Permeation Test (IVPT) Methods: Best Practices and Scientific Considerations for ANDA Submissions. MedPharm’s chief scientific officer Jon Lenn, and our senior director of bioanalytical Kendall Powell will be two of the experts weighing in on topics ranging from diffusion cell apparatus to IVPT studies during topical product development.
OSP: Could you please share an overview of MedPharm—who you are, what you do, key specialties/capabilities, and how you might help companies seeking to launch topical bioequivalents navigate these challenging waters?
OSP: MedPharm is a topical and transdermal drug development service provider. We are experts at reducing risk and accelerating development times for generic and proprietary pharmaceutical customers through our unique, cost-effective, and industry-leading performance testing models.
Well established as the global leader in dermatology, nail, mucosal membrane, and transdermal product development, MedPharm also offers innovative solutions for ophthalmic and airway preparations. MedPharm has fully established Centers of Excellence in the USA and the UK.
Regarding generics, we support our clients by producing data and supporting arguments to regulatory authorities during scientific advice and pre-ANDA meetings. Our approach focuses on the smallest data set required within the regulations required for approval. Unlike many CRO’s, MedPharm provides comprehensive feedback on all projects, often undertaking formal gap analyses to improve formulations or regulatory submissions.
OSP: Anything to add?
LA: We have recently opened our new manufacturing site in Durham, North Carolina for clinical and small scale commercial topical manufacturing. We have also opened our US offices to visitors.