Building an affordable innovative drug development chain

Voisin Consulting is France-based strategic regulatory consultancy firm, which set up their India office in Bengaluru in 2008. Dr Emmanuelle Voisin, Global CEO, Voisin Consulting spoke to Viveka Roychowdhury on the trends in regulation and how India fits into her plans for build an affordable innovative chain, from discovery to market

Could you give us a background on Voisin Consulting?

We assist biotechnology, pharmaceutical and medical device companies in the design and implementation of innovative regulatory strategies to expedite product development. We assist them achieve marketing authorization (MAA/NDA/BLA) which will allow them to go to market(s). We are operational in the US, Europe, Switzerland, Australia, Singapore and now in India.

Every time there is a new regulation requested by the government, or generated by the industry needs, our scientific and technical contributions not only help us to remain updated but also aware of the philosophy underlying new regulations. We are the bridge between science and regulations in our interaction with regulatory bodies. We also participate in the working groups of regulatory agencies like EMEA, US FDA, where discussions lead to future regulations. Flowing from this innovative regulatory approach, as we collaborate with regulatory agencies, we put these inputs into the product development of our clients so that we ensure a timely development customised to the product type. Thus lean drug development is another of our characteristics.

Where does India fit into your global business model?

My main objective right now is to create partnerships with Indian companies in different areas. And my coming to India is not for cost-savings but to identify excellent partners, high quality service providers, to build long-lasting durable relationships. India possesses skilled people and high potential for drug development. Not just for Voisin Consulting, but for our clients wishing to outsource to India. We want to build an innovative chain, from discovery to market by putting together all the pieces of the puzzle to make an affordable drug, from formulation development, manufacturing to clinical, and to market(s). Our clients will not have to go through the trial and error process to identify potential partners as we will have already taken time to do a due diligence and identify the most appropriate partners. But India is not a part of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (jointly referred to as PIC/S), ICH, GCP mutual recognition which is a drawback today.

You were a speaker at DIA's 4th Annual Conference On Drug Discovery & Clinical Development in India. What were the key takeaway messages from the regulators who presented at the conference?

The key message from the US FDA officials who spoke at the conference, (Bruce Ross, Director and Albinus D'Sa, Deputy Director, US FDA based at New Delhi), was that the US FDA has the will to collaborate with the office of Drug Controller General (India) (DCGI) and to facilitate the development of products out of India for the US market.

Also of particular importance was the fact that Agnes Saint Raymond, Head, Scientific Advice & Orphan Drug Sector, Pediatric Medicinal Products, EMEA and Timothy Cote, MD, Director, Office of Orphan Products Development, US FDA made the case that Indian pharma industry should go for orphan drug submission to Europe and the US. Orphan drugs could also mean certain neglected diseases like malaria, tuberculosis, leishmaniosis, dengue fever which are by definition orphan diseases in the US and EU (that it affects less than 200,000 people in the US and 5/10,000 people in Europe).

What I found interesting is that today, the senior officials from FDA have actually worked in developing countries in previous postings so they actually know the ground realities of the neglected diseases.

I spoke on biosimilars and their evolving regulation. Today, in Europe, there is a clear realisation that since biosimilars are not new products, companies can benefit from a reduction of effort and time in the development cycle. However, biosimilars cannot be considered the same as generics, as these are complex molecules liable to be glycosylated, for example, and this can completely change the safety and efficacy profile of the product. Therefore since the process makes the product in biotechnology, you cannot consider a biosimilar identical to the reference product. They are similar, but not the same. The more complex the molecule, the more difficult it is to prepare a biosimilar version of it (e.g. monoclonal antibodies). The European regulation on biosimilars is the most advanced as we already have a set of guidelines, including some specific to certain products. The most recent one released was a "Concept paper on the development of a guideline on similar biological medicinal products containing monoclonal antibodies". There certainly will never be a 'cook book recipe' for biologics! Looking ahead, there will be learning experiences through the development process of MAbs.

What are the challenges posed by orphan drug development and how can these be made to work to the advantage of mid-size or SME pharma players in Europe?

EU standards for the evaluation of orphan drug development are as high as for non-orphan drugs, i.e. the quality of the data needs to be very high, the benefit-risk ratio assessment conducted with care and of course the outcome should be a positive ratio (benefit outweighing risk). Requirement for well designed randomized clinical studies is one of the major challenges, given the difficulty in recruitment of certain diseases. Nevertheless, in practice there is room for justification of non-standard development strategies, when science drives the development.

Products which are granted orphan designation are required to go via the centralised procedure for MAA assessment (mandatory route); once granted, the marketing authorisation is therefore valid in all EU Member States, which can be considered a major advantage for smaller companies. Also, sponsors of orphan medicinal products benefit from a number of incentives including significant fee reductions at the time of the MAA submission (50 percent fee reduction for an orphan drug and 100 percent fee reduction for an orphan drug developed by a company which has obtained the SME status from EMEA). Today, one of the challenges faced with orphan products in Europe is the fact that the approval process is working efficiently, but the price and reimbursement issues slow down the launch of the product in certain countries. This leads to uneven access to these products by patients with unmet medical needs. From a business perspective, a number of new companies have been created focusing exclusively on researching and developing orphan drugs, partly resulting from the EU Orphan Regulation.

What are the ethical issues posed by the access or no access to orphan drug ?

Access to orphan drugs is a major concern for all stakeholders, not only for physicians and regulators; this translates into for example the increasing number of Member States which have implemented or are in the process of implementing some form of national plan for rare diseases. France, in 2005, was the first country to have implemented a formal National Plan. Also, some countries have been particularly flexible in accommodating the use of new orphan drugs in their health care system.

Are the number of orphan drug approvals increasing?

With regard to the number of medicinal products granted orphan status, there a clear increase in numbers (26 COMP positive opinions in 2000, 101 in 2009 as of November 09). The latest COMP press release (dated 17 Nov. 09) mentions that for the first time the COMP designated more than 100 orphan medicinal products in one calendar year.

With regard to marketing authorisation of orphan drugs, there has been an increasing trend in activity around rare diseases/orphan drugs over time. Since the adoption of the EU Orphan Regulation, the number of marketing authorizations for orphan drugs has increased almost every year: from eight "orphan drugs" before the EU Orphan Regulation to 47 products by the end of 2008 in the EU in total, mainly in the area of oncology and metabolic disorders.

viveka.r@expressindia.com