APIs – global business developments

APIs – global business
Gian Mario Baccalini
EFCG Board Member, Chairman of EFCG Pharma Business Committee
President & CEO, Euticals S.p.A., Italy
EFCG Press Conference, 22° October 2013, CPhI Frankfurt
Features of the European API
• High level of competence in fine chemistry
• Employ a range of skilled, qualified & experienced staff for:
 Early assessment of market opportunities
 All technical (incl. ESHQ) management requirements
 Handling Intellectual Property Rights (e.g., patent issues)
 Production compliance with Good Manufacturing Practices on
the basis of inspections performed by Regulatory Authorities
Where do the European
manufacturers stand?
 APIs market is more and more a worldwide business, integrated
in the supply chain
 Manufacturers of APIs give more value to their production
towards the dosage form
 Companies increase their size
 Manufacturers in new countries put more pressure on the
market, for instance: Turkey, Eastern Europe, Middle East
 Opportunities and challenges of selling APIs to BRICs countries
As we are in a global market, we need to establish a global
Some figures
 Word market APIs: 37.0 billion US $
 European APIs production: 14.0 billion US $
 Italian market share APIs worldwide: 12%
Activities of European manufacturing:
 50% custom manufacturing
 50% generic medicines
New Legislation affecting APIs
Global Business Developments
Falsified Medicines Directive (FMD), 2011/62/EU
Came in to force on 2nd July, 2013
Generic Drug User Fee Act (GDUFA)
Came into force on 1st October, 2012
The Falsified Medicines Directive (FMD)
• All EU countries should have transposed the FMD
into national rules of the FMD within 18/24 months
from its publication in the Official Journal (1st July,
• As of 18° October, 23 of 28 Member States have
• 5 Member States face infringment proceedings from
the European Commission.
• Some countries judge the Directive too strict and
others too lenient ( a health risk for EU citizens!)
Present legislative situation
 The current Directive covering human medicines does NOT ensure that
the APIs used in EU comply with European GMP wherever they are made
 Use of many non-EU API sites is dependent on industry self-evaluation and
open to corrupt practices
 Over 70% of all APIs sold in EU now come from non-EU sites
 Now clear that the number of non-EU API sites is very much less than the
EC had assumed (<1500 vs. 15,000-20,000)
 Mandatory inspections of EU API sites are performed by EU Regulatory
Authorities but there are no mandatory inspections of non-EU API sites
FMD situation at 18th October
 23 Members States had transposed into national law flexibility exists as it is a Directive not a Regulation (like REACH)
 EU Equivalence listing countries: USA, Switzerland, Japan, Australia
approved with others pending incl. Brazil, NZ, Singapore
 8 Member States (SP, IT, IRL,UK, GE, RO, FR, GR) using 2° waiver
(Art.46(b)4) using EU GMP inspections to avoid shortages
 No reported shortages of critical raw materials medicines but may
happen once EU stocks depleted
 ~1500 non-EU sites identified in Top 18 countries exporting bulk APIs
to the EU. Most are issuing Written Confirmations
 China and India severely limited the number of sites allowed to export
to the EU via Written Confirmations
 Some Indian sites were reported to be non-compliant with EU GMPs
and have been stopped by EU from exporting.
EFCG Proposals
What needs to happen?
 Stricter enforcement by EU authorities plus tough
sanctions to punish offenders
 Train inspectors to detect falsification and fraud
 Consistent approach to transposition by Member States
 APIs in imported finished/semifinished products are
subject to the same rules as imported bulk APIs
 Either change in the law to include mandatory inspections
paid for by industry if needed (cf. GDUFA/USA)
 Or arrange Mutual Recognition Agreements with those
countries with EU GMP standards (with USA, as with
Australia and Switzerland MRAs are «fully operational»)
Generic Drug User Fee Amendments
GDUFA – FDA Progress Report - June 2013
• Collected $255m year 1 user fees. Goal $299m
• Hired 165 new staff
• Helped industry self-identification which made
accurate fee calculation possible
• Improved the quality of generic industry supply chain
• Reduced the backlog of pre-GDUFA applications &
adjusted internal processes
• Established GDUFA Steering Committee to implement
review programme enhancements
• Set out GDUFA FY14 Regulatory Research Priorities
Implementation experience
• Some learning curve but no major issues
• Timely and effective FDA communication tools
• Supportive education role from EFCG, SOCMA,
• Increased workload in regulatory departments to
update DMFs for Completeness Assessment
• Training required across different departments
Top benefits rated by API producers
 Level Playing Field
 Equitable Oversight, Quality Standards, Compliance
 Reduce the timelag – development to commercialisation
 Improve direct communication with DMF reviewers
 Regulatory Science involvement
EU-US Transatlantic Trade & Investment
Partnership (TTIP)
October 2012:
EFCG, APIC & SOCMA filed a proposal with both the EU and US
government negotiators on MRAs for GMP Inspections
April 2013:
EFCG, APIC & SOCMA presented their case in Washington DC
along with all other pharma trade bodies
Outcome: Agreement that all EU & US pharma trade bodies
wanted the same thing – MRAs for GMP Inspections
July 2013:
EU Pharma trade bodies briefed DG Trade on their needs from
TTIP ahead of 1st round of negotations in Washinton DC
October 2013:
2nd round of negotiations cancelled due to US Shut Down.
EU-US Transatlantic Trade & Investment
Partnership (TTIP)
Letter to DG Sanco, EMA, DG Trade, 31° July, 2013
Subject: Call for the Pursuit of a Mutual Recognition Agreement on Good
Manufacturing Practices (GMP) Inspections in the Context of an Ambitious
and Comprehensive EU-US TTIP Negotiation
“…..we wish to highlight one important recommendation that has been
proposed by all of our organisations, namely completing a Mutual
Recognition Agreement (MRA) on GMP Inspections.
An MRA on GMP Inspections between the EU and US will have an immediate
positive impact on the resources of the regulatory agencies, the European
Medicines Agency (EMA), National Competent Authorities (NCAs) of the EU,
the Food and Drug Administration (FDA), and on the industry.
The resource savings for regulators should allow for the agencies to work
together to identify high-risk sites in need of inspection, including in third
countries, and to ensure resources are committed to addressing this need.”
1. FMD
The implementation of mandatory inspections, via an MRA
approach, is a relatively small price to pay to guarantee the
quality of API meets the EU standard, irrespective of its global
source, for the benefit of the health of the EU citizen and of the
EU API manufacturing industry.
Good progress toward agreed 5 year objective.
Progress is slower than expected but objective of MRAs for GMP
Inspections remains our high priority.

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