Avivia is not your traditional pharmaceutical development CRO. We are much more than that. Although we do offer the typical ad-hoc analytical and pharmaceutical development services, we often perform full development programs where we take up projects right from start and deliver product solutions custom-made to the needs and interests of our clients. Our approach is fully integrated and combines hands-on pharmaceutical and analytical development work (formulation & CMC) with high-standard regulatory, intellectual property and market access support.
Our expertise and capabilities are centered around the development of value-added generic drugs, life cycle management of branded drug products, and complex formulation and CMC development of new drug products (NCE).
A division of Avivia BV – Experts in excipient characterization
Excipia is a knowledge platform commenced after experiencing the disadvantageous consequences of unpredictable reactivity and batch-to-batch variability of some widely used excipients during drug formulation development. The observed excipient performance could not be or related to or explained by the typically limited information on the Certificate of Analysis of these excipients.
Within Excipia we have therefore setup numerous analytical procedures to investigate the physicochemical composition of a broad range of excipients and reveal undesired ‘hidden features’. With the Excipa platform we can examine batch-to-batch product performance variations, implement excipient related Quality by Design (QbD) approaches, perform quantitative deformulation and competitor research and analysis, monitor site changes or manufacturing process optimization, and select excipient batches to improve drug product performance without the necessity to change a registered drug product formulation.
Excipia offers hands-on troubleshooting services and solutions to pharmaceutical, generics, drug development and food companies that are encountering problems with stability, dissolution profiles, reproducibility, batch variations, etc.
Avivia offers full product development services to generic drug companies and specialty pharma focused on the development of new improved versions (value-added generics or generic plus) of established drug products. Typically, our clients approach us with a specific development request but occasionally, we are also asked to investigate and propose new product opportunities based on the existing drug portfolio of our clients. Although in general the overall aim of value-added generic development projects is focused on improving the safety, efficacy and/or the ease of administration, we are also specialized in executing development programs where the primary or sole objective is the evasion of existing product patents.
Case study – Reformulation project
Pouchitis is the most frequent complication of ileal pouch-anal anastomosis (IPAA). In Europe and the United States, the condition is estimated to affect the lives of respectively 150.000 and 80.000 patients.
In collaboration with the Department of Gastroenterology of the University of Leuven, Avivia BV has developed a modified release formulation of metronidazole (MRZ) for the treatment of pouchitis. This formulation aims for a lower systemic and higher local exposure to MRZ, with non-inferior efficacy to standard of care MRZ immediate release (IR) yet at a lower dose making for a more effective treatment with decreased treatment burden, increased quality of life for patients and the potential for chronic or repeated treatment episodes.
The socio-economic impact is related to the avoidance of expensive and burdensome additional surgery and treatments (e.g. biologics) as well as a reduced evolution to chronicity.
Orphan drug designation of MRZ for pouchitis has been granted by the FDA and the COMP.
Our ‘life cycle management’ development services are focused on maximizing the value of your drug during its product life cycle. Typically, we are asked by pharmaceutical and biotech companies to develop new product formulations of branded drugs to anticipate on patent expiries, generic competition and profit erosions. Besides hands-on formulation and CMC development work, we also provide specialized analytical, regulatory, intellectual property and competitive intelligence solutions in order to proactively plan your molecule’s path to success from the start.
Case Study – Evolution towards fixed dose combination therapy
Artemisinin based monotherapy, a therapy using one active compound, has been extensively used in Asia and Africa in the ongoing battle against Malaria. A short treatment course of 5 days is sufficient to cure a patient but reoccurrence in this case is fairly common. In order to avoid risk of drug resistance, the WHO recommended to develop Fixed dose combination therapies whereby Artemisinin compounds are combined with other drugs with different modes of action.
Based on a thorough literature overview, we postulated that a combination of artesunate with pyrimethamine (a dihydrofolate reductase inhibitor) and sulfamethoxypyrazine (a dihydropteroate synthase inhibitor) all combined in one tablet could form an ideal combination.
The combination product is safe for children and pregnant women, the elimination half-lifes of the drugs overlap nicely to keep up the synergy of the different mode of actions and the resulting tablets are stable under tropical storage conditions.
We subsequently filed a patent, developed the product in house and the client performed several clinical trials in Africa to show the effectiveness and safety of the novel FDC product with very good results and the product was registered all across Sub-Saharan Africa.
For many years, the product has now been available in the private market in Africa, generating steady sales.
Avivia is known amongst the drug development community for being able to deliver successful solutions for complex and challenging formulation and CMC development projects. Typically, pharmaceutical companies and smaller drug development firms approach us with development programs that have derailed or – in the worst case and despite all previous efforts – have reached a dead end. Besides hands-on formulation and CMC development work, we also provide specialized regulatory, intellectual property and competitive intelligence solutions in order to proactively plan your molecule’s path to success from the start.
In the field of complex formulations we have recently worked on nano-emulsions, pH-modified release dosage forms, hydrogels, solid dispersions, melt extrusion, 3-D printed tablets, a 4 component medicinal product, switching an injectable into a sublingual tablet, solving stability problems of IV solutions, improving bioavailability and solubility of particular drugs, failing bioavailability studies, taste masking in oral formulations, etc. .
Before we start any collaboration (being a full development program or a stand-alone service), it is of the utmost importance that we have a thorough understanding about the product itself (including all available data) as well as about the product portfolio and commercial strategy of our client. We therefore start every interaction with one or more face-to-face or telephone meetings in which all such aspects are discussed. Based on the information provided by our client, we investigate internally the different product development strategies in order to make a tailored-made project proposal. Once the proposal is approved by the client and integrated into a formal collaboration agreement, the project is initiated.
Typically, our project plans are structured in multiple phases with relevant go/no-go decision points. At pre-defined stages during the execution of the project, the client has the option to decide whether or not to proceed with the current project, and/or to apply alternative development approaches. In this way, we can work together with our clients in the most flexible, cost-efficient and result-oriented way.
A critical factor to ensure a successful execution and completion of our projects is a direct and transparent communication between all parties involved. Before the start of each project, a detailed protocol plan is prepared and agreed upon, while during the project execution itself, frequent updates are provided to our clients allowing close monitoring and/or rapid adaptation of projects. Upon completion of each project, a detailed report is provided to the client.
We are open to apply different types of commercial collaboration structures. Full development projects can be performed either on a pure fee-for-service basis or through co-development where we provide the services at cost-price and include a single success-driven milestone payment and a small royalty payment. Stand-alone project services are always performed on a fee-for-service basis.
If you are interested to learn more about our development services, feel free to contact us and we would be happy to organize an introductory meeting or call with our team of experts.