Biotechnology & Pharmaceuticals 2018 EXPERT GUIDE www.corporatelivewire.com
Contents 4 6 Introduction SNAPSHOT: Biotechnology in the UK 8 An Expert Discussion On: Minimising Risk of Litigation By Nicola Dagg, Madeleine Kearney, Eliana Moraes, Nicola Baker-Munton 12 Newest Amendments To The Examination Guide For Patent Term Extension By Yu-Li Tsai 16 What about biotech patentable subject matter in Colombia? By Andres Rincon 20 24 Interchangeability of Biosimilars in Brazil By Angela Fan Chi Kung & Camila Martino Parise Expert Directory Fenice Media Ltd 101 The Big Peg 120 Vyse Street Birmingham West Midlands B18 6NF United Kingdom Tel: +44 (0) 121 270 9468 Fax: +44 (0) 121 345 0834 www.corporatelivewire.com Chief Executive Officer Osmaan Mahmood Managing Director Andrew Walsh Research Managers David Bateson Chris Barry Editor-in-Chief James Drakeford Art Director Timothy Nordan Senior Designer Dan Harvell Senior Writer Richard Hobson Marketing Development Manager Dilan Parbat Administration Managers Jenny Njuki Data Administrators Dan Kells Data Administrators Tom Wisniewski Ryan Winwood Publishing Division Jake Powers John Hart John Peterson Awards Directors Kevin Norden Benjamin Pugh Max Bond Clint Stevens Awards Coordinators Roxana Moroianu Alan Davis Roy Johnson Account Managers Norman Lee Rocky Singh Kerry Payne Michael Barker Vinny Bindra Head of Finance Joseph Richmond 2 January 2018
6 8 16 20 Senior Credit Controller Michael Atkinson Credit Controllers Ben McPhillips Jack Speed Contributing Organisations Deep & Far Cavellier Pinheironeto Advogados January 2018 3
Introduction Introduction Technological advancements have enabled biotechnology and pharmaceutical companies to develop new and innovative products at breakneck speed. However, even after clinical testing and human trials, there is still the risk of adverse effects emerging which oftentimes exposes the company to, amongst other concerns, class action litigation. In this guide, we have included an expert discussion aimed at identifying the various measures that can be implemented to help minimise the risk of litigation in the biotechnology and pharmaceutical sector. Aside from action litigation, another prominent challenge facing biotechnology and pharmaceutical companies is the issue of intellectual property. Ever since the infamous patent cliff era of 2010-2013, generic drug manufacturers are waiting in the wings as each year brings a fresh batch of patent expirations for blockbuster drugs. According to Dickson Data, at least four drugs with annual estimated revenue above $1bn were going off-patent in 2017 (Sandostatin LAR $1.6bn; Cubicin $1.17bn; Reyataz $1.14bn; Vytorin $1.12bn) whilst they also calculate that branded drugs lose up to 90% of their sales when generics make it to market. It is no wonder big pharmaceuticals are keen to protect their patent at all costs. With this in mind, Yu-Li Tsai summarises the changing market conditions in Taiwan following recent amendments to the examination guide for patent term extension. We also consider biotech patentable subject matter in Colombia. As a result of recent regulatory developments, we have seen a shift in landscape for the biosimilar sector in Brazil. Having previously offered a summary of the sector in last year s guide, the team at Pinheiro Neto Advogados have returned to provide us with an updated overview of the current market outlook. 4 January 2018
Brazil Angela Fan Chi Kung akung@pn.com.br +55 11 32478400 www.pinheironeto.com.br Camila Martino Parise cparise@pn.com.br +55 11 32478499 www.pinheironeto.com.br Interchangeability of Biosimilars in Brazil By Angela Fan Chi Kung & Camila Martino Parise In Brazil, biological products are regulated by the Brazilian Health Regulatory Agency ANVISA pursuant to Resolution RDC No. 55/2010, and are defined as product containing a molecule with known biological activity, which has passed through all manufacturing steps. A molecule not yet approved in Brazil is called new biological product, while a molecule already registered in Brazil is called biological product. Brazilian regulation has not embraced the expression biosimilars, like United States and Europe. Approval of new biological products requires a complete technical and scientific registration dossier. Biological products, in turn, have two approval pathways; individual development or comparability. In the individual development pathway, the applicant must provide ANVISA with a complete technical and scientific registration dossier including clinical and non-clinical data and immunogenicity studies. Except for blood products, vaccines and biological products with oncological indication, in the registration process by the individual development pathway, the phase III clinical studies shall attest the non-inferiority, equivalence or superiority of the biological product in relation to the new biological product. Also, the safety and efficacy data presented to AN- VISA cannot extrapolate to other therapeutic indications not approved for the new biological product. In the comparability pathway, the biological product is approved upon comparison of its efficacy and safety attributes with a comparator product already approved by ANVISA, and requires comparative pre-clinical and clinical studies to evidence the biosimilarity between the comparator and the biological product products. The extrapolation of safety and efficacy data for other therapeutic indications of the biological products recorded by comparative development pathway, however, is allowed, and the conditions must be established in specific guides issued by ANVISA. In either pathway, ANVISA does not require any specific showings required for an interchangeability determination. Recently, ANVISA, through Technical Opinion 003/2017/GBIO/GGMED/ANVISA, stated that the interchangeability is not a requirement for registering a biological product but a medical practice that should be analysed considering the patient s clinical scenario. For ANVISA, biosimilars and comparators interchanging must be decided by the prescribing physician and the Ministry of Health. Once the comparator biological product is replaced by the biosimilar, medical assessment and oversight are essential to find what product best fits based on the patient s response. 20 January 2018
Accordingly, ANVISA has already advised that, upon registration of a biosimilar, it will not classify or determine what the interchangeable biological product is for the relevant product given such classification may involve assessment of data other than those required by legislation. Nor does the agency believe necessary to issue a specific regulation to govern this matter. In 2015, ANVISA started to publish in its website a document called Drug Approval Public Opinion, which describes the technical and scientific arguments used by the Agency in reviewing the dossier for registration of drugs approved thereby. In case of biological products, such document does not provide information about the studies that could be used to evaluate the interchangeability of biossimilars and the comparator. ANVISA, however, believes prudent to include such information in its public opinion, and also in the label of the product since, it may assist the interchangeability exercise. However, no specific regulation has been issued by the Agency in this regard up to this moment. January 2018 21
United Kingdom Brazil is working in an effort to reach a consensus in relation to the interchangeability, and, in the present moment, for ANVISA, the prescribing physician, responsible for the patient s assessment and oversight, is the most relevant factor in case of interchangeability between biosimilars and their comparators. ANVISA defends that the patient s assessment and oversight by the prescribing physician is the most relevant factor in case of substitution or interchangeability between biosimilars and their comparators, mainly for purposes of pharmacovigilance and postmarket oversight. In addition, multiple alternation between biosimilars and the comparator product must be avoided not to impair traceability and oversight of the product use. The subject has been gaining ground, including in the national political environment. The Social Affairs Committee of the Senate, in order to gather information on the possibility of changing the comparator by the biossimilar to guarantee their safe and effective use, at more affordable costs to patients, launched a Public Hearing on 15 August 2017 to discuss the matter. The medical class then expressed their discomfort with ANVISA s stand and is pushing for a regulation. The main argument is that biosimilar product substitution requires additional clinical evidence and such decision cannot be left in physicians hands. The government, in turn, worried about the costeffectiveness ratio, at said public hearing, and stated that increasing access to biosimilars with proof of interchangeability and possibility of automatic substitution would also increase access and consequently bring benefits to the population and to the Brazilian health industry. Brazil is working in an effort to reach a consensus in relation to the interchangeability, and, in the present moment, for ANVISA, the prescribing physician, responsible for the patient s assessment and oversight, is the most relevant factor in case of interchangeability between biosimilars and their comparators. 22 January 2018
Expert Directory Expert Directory Taiwan Colombia Brazil Deep & Far Yu-Li Tsai yltsai@deepnfar.com.tw +886 2 2585 6688 #8139 www.deepnfar.com.tw Cavellier Andres Rincon andresrincon@cavelier.com +57 347 3611 Ext. 2269 www.cavelier.com Pinheironeto Advogados Angela Fan Chi Kung akung@pn.com.br +55 11 32478400 Camila Martino Parise cparise@pn.com.br +55 11 32478499 www.pinheironeto.com.br 24 January 2018