Little known facts about SourcingComparators from Emerging Markets with Confidence

By

DR. PIYUSH GUPTA (MBBS, MBA)
ASSOCIATE DIRECTOR – BUSINESS DEVELOPMENT
GNH INDIA
MUMBA, INDIA

Index

1. Facts: Biosimilar Opportunity 2020
2. Facts: About Biologics
3. Global Regulatory Pathway
4. Comparator Examples From Market
5. Key regulations governing comparator sourcing
6. Comparator Souring Organisation – Roles and Services.

1. Facts: Biosimilar Opportunity 2020
   
   • Biologic drugs with sales over $100 billion set to loose patent by 2020.1
   • Over 3000 companies globally are in the race to develop Biosimilars / Biobetters
   • Over 1300 biosimilars candidates under development
   • The demand for Comparators / RLDs has been estimated at 500,000 units for phase 1 trial through Phase III trials!
2. Facts: About Biologics
   • If Aspirin’s molecular mass is 180 daltons, that of a Biologic such as mABs is more than 150,000 daltons

   

   

   Facts: About Biologics – complex manufacturing process

   

   Facts : Biologic Manufacturing

   • Every Biologic product displays a certain degree of variability even between different batches of the same product.
   • Even minor changes in production process have to approved by NHAs
   • For example, Genzyme opened a new large plant in an attempt to produce Myozyme (alglucosidase alfa), but the FDA did not consider the product in the new plant to be the same as Myozyme.
   • Instead, Genzyme had to get approval from the FDA through a BLA (Biologic licensing application) for an entirely new biologic, Lumizyme (alglucosidase alfa), which was produced at the new plant. This resulted in a better biologic with new exclusivity.

Facts: Inherent Variability



3. Global Regulatory Pathway

   How does a Biologic travel from SRA to Emerging Market
   

   

   

   Pathway to Emerging Markets: Product registration Module 1 – CPP and FSC
   

   

   What does a CPP look like ?
   

   

   Regulatory – Registration

   • Module 1 – General Information:

   One of the most important requirement of module 1 is CPP (Certificate of Pharmaceutical Origin). CPP is a certificate developed under WHO (World Health Organisation) Certification scheme in 1975 and most recently revised in 1997.Detailed information can be read here : http://www.who.int/medicines/areas/ quality_safety/regulation_legislation/certification/guidelines/en/

   • CPP requirement as adopted by Indian CDSCO: here : http:// www.cdsco.nic.in/writereaddata/Guidance%20documents.pdf. CPP is a mandatory certificate in all CTD dossiers and is taken as a proof of QSE (Quality, Safety and Efficacy) of the product and also as an evidence of GMP.
4. Comparator Examples From Market

   Sourced from USA

   

   Authorised in USA

   

   Sourced from France

   

   Authorised in France

   

   

   

   Taking a product from SRA to Emerging Market

   

   Is this possible without CPP, eCTD, Registration pathway ?
5. Key regulations governing comparator sourcing

   Regulatory Senario – USA

   • Important act governing Biologic and Biosimilar Trade:
   • Biologic price competition and innovation act. http:// www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/ ucm216146.pdf
   • Over 110 reference made in this act to “Reference” product (Comparator).
   • Important restriction: (5) General Rules (A) – One reference product per application.
   • Important act governing Biologic and Biosimilar Trade:
   • Guidelines on Similar Biological Medicinal product:http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf
   • Section 3.2: Choice of reference product:
   • Restriction: “The reference medicinal product must be a medicinal product authorised in the EEA, on the basis of a complete dossier in accordance with the provisions of Article 8 of Directive 2001/83/EC, as amended”
   • “However, with the aim of facilitating the global development of biosimilars and to avoid unnecessary repetition of clinical trials, it may be possible for an Applicant to compare the biosimilar in certain clinical studies and in in vivo non-clinical studies (where needed) with a non-EEA authorised”
6. Comparator Souring Organisation

   CSO – Comparator Sourcing Organisation

   • Why CSO ?
   • Sourcing of Reference drugs / Comparators has become an “Achilles Heel” of this industry.
   • Ask for 1000 pack – Sorry we offer only 50.
   • Ask for 3 batches – Sorry we have only 1 batch.
   • Ask for CoA – Sorry not provided.
   • Because Sponsors and CROs should be able to focus on trials.
   • CSO such as GNH India a specialised wholesaler of Drugs who understand the complex global regulatory frame work and can help Sponsors and CROs cut cost
   • We navigate the treacherous path of comparator sourcing for you, so you could FOCUS on Development.
   • A 1000 packs – Done
   • 3 Batches – Done
   • CoA, CoC, Pedigree dossier, Temperature record, Recall Agreement –DONE
   • Ship to Timbuktu – Done
   • Cost effective sourcing from Emerging markets can bring this down to 5 – 10%