Post on 10-Aug-2020
REGULATIONS | ENFORCEMENT | GLOBALIZATION | SECURITY & INTEGRITY
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PART I Regulations: USA Europe Asia International
PART II Enforcement Globalization Supply chain security Case studies Summary
The role of Asian producers Special 301 report & Priority Watchlist Japan: ICH guidelines Japan: JPMA codes and guidelines Japan: Pharmaceutical Affairs Law India: IPR policy & the Patent Act India: Pricing policies & authority India: Compulsory licensing India: GDP guidelines of 2013 China: IPR & counterfeit products China: Good Supply Practices Russia: emerging market Russia: IPR & pricing policies Russia: 429-FZ
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JAPAN
INDIA & CHINA
Top 25 global brand manufacturers
Takeda Astellas Otsuka Daichi Sankyo Eisai
• Hundreds of approved manufacturing facilities
• Major challenges in drug supply chain integrity and security and IPR protection
• 50% of U.S. drug master files come from India & China
• IPR and trade secret protection & enforcement
• Priority Watch List: India, China, Russia
• Most counterfeit drugs shipped to the U.S. come from India and China
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INDIA
• Priority Watch List in 2015
• IPR Working Group established
• Procedural safeguards to protect trade secrets
• Support of India’s enforcement efforts
• Draft National IPR policy in January 2015
• Securing and enforcing patents
• Greater regulatory coordination
• Situation in counterfeit drugs very troubling
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INDIAN PATENT LAW
An “invention” is any product or process that is novel, has an inventive step, and is capable of industrial
application.
Section 3(d) of India’s Patents Act states that “the mere discovery of a new form of a known substance which
does not result in the enhancement of the known efficacy of that substance” is not considered to be an
“invention”.
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INDIAN COMPULSORY LICENSING LAW
India has made clear that it views compulsory licensing as an important tool of industrial policy.
In the United Nations Framework Convention on Climate Change negotiations, India continues to
identify patents as obstacles to the dissemination of green technologies.
Merck v. Glenmark
Cipla v. Roche
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TRADE SECRETS PROTECTION
• Difficulty in obtaining remedies and damages
• Reliance on contract law
• Theft by business competitor not covered
• Trade secrets disclosed during judicial proceedings
• Theft of undisclosed test data generated in clinical trials
• Significant delays associated with cancellation and opposition proceedings at the Trademark Registry.
• The amount of counterfeit goods remains very troubling.
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LOCALIZATION IN INDIA
• Local manufacturing favored
• Pricing restrictions on more than 500 formulations
• Indigenous medicines can be priced higher
• Compulsory licenses if a patented product is not manufactured in India
• Import restrictions on narcotics
• India is a net exporter of drugs and biologics
• Indian Department of Pharmaceuticals actively promotes Indian products globally
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GMP CERTIFIED PLANTS IN INDIA
• Government support for GMP certification
• Hundreds of WHO, FDA, EDQM, MHRA and TGA compliant plants
• Important exporter of generics and high-value products
• Major share of produce exported to highly regulated markets
• Multiple Warning letters from the FDA recently
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GDP GUIDELINES
Distribution is an essential activity in the integrated supply-chain management
Multiple individuals and entities are responsible
Adequate controls over the entire chain of distribution are essential
Every party involved has to comply with the applicable requirement
Risks: mix-ups, adulteration, contamination, cross-contamination, and degradation.
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GDP GUIDELINES : OBJECTIVES
The objective is to ensure the quality uniqueness of pharmaceutical products during all aspects of the distribution process:
Procurement
Purchasing
Storage
Distribution
Transportation
Documentation
Record-keeping
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GDP GUIDELINES : APPLICABILITY
• Manufacturers of APIs and finished products
• Wholesalers, suppliers, distributors
• Government institutions
• International procurement organizations
• International donor agencies
• Certified bodies
• Logistics providers, traders, transport companies
• Health workers
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Drug & Cosmetics Act of 1940 Cosmetics Rules of 1945 Rules for sale, promotion and distribution of pharmaceuticals
All parties are jointly responsible for
Quality of pharmaceutical products
Integrity of the supply chain
Obligation to collaborate applies to government agencies, customs, regulators and law enforcement
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GDP GUIDELINES : DISTRIBUTORS
• Authorizations for distributors
• Import/export licenses
• Sourcing from authorized persons only
• Supply to authorized persons only
• Subcontractors are held to the same standard
• Organizational charts indicate relationships and responsibilities, linked to job descriptions
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GDP GUIDELINES : PERSONNEL
Designated person
Has to have the authority and responsibility to implement and maintain a quality system
Managerial and technical personnel
Have to have the authority and resources to carry out their duties
Personnel shall not be subject to pressures that would compromise quality of the product
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GDP GUIDELINES : PROCEDURES
Safety of personnel and property
Protective garment (high-potency products)
Environmental protection
Product integrity
Initial and continuing training on GDP:
• Product handling
• Product safety and security
• Product identification
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GDP GUIDELINES : RESPONSIBLE PERSON
Responsible person for each distribution site
Implementation and maintenance of a quality
system
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GDP GUIDELINES : CAPA
Deviations from established procedures:
Document
Investigate
Implement CAPA
Procedures for procurement and release
Sourcing
Supply
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GOOD STORAGE PRACTICES
Unusable and hazardous products separate
Storage conditions as labeled by manufacturer
Non-compliance shall be investigated
Precautions against spillage, breakage, theft
Narcotics in secure containers
Container labels contain all necessary info
Procedures for dispatch to ensure traceability
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GDP: RECORDKEEPING
Data integrity and veracity
Validation and backup
Handling of detected spurious products
Notification requirements
Audits and self-inspections
Corrective and preventative measures
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CHINA IPR AND INNOVATION COMMITMENTS
Joint Commission on Commerce and Trade (JCCT)
U.S. - China strategic and economic dialogue (S&ED)
The WTO Dispute Settlement Body ruling (March 2009):
• Denial of copyright protection violates the TRIPS Agreement;
• Seized counterfeit goods cannot be publicly auctioned after only removing the spurious trademark.
• Criminal enforcement measures must reflect and respond to the realities of the commercial marketplace
• In March 2010, China announced that it had implemented the rulings.
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USTR SPECIAL 301 REPORT: CHINA
• Priority Watch List in 2015
• Commitment of China to protect and enforce IPR
• Ongoing overhaul of Chinese IPR laws
• Major source of counterfeit pharmaceuticals
• China and India are the main source of counterfeit pharmaceuticals shipped in the U.S.
• China ships counterfeit drugs also to Africa
• Counterfeit drugs are a major public health problem.
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IPR VIOLATIONS IN CHINA
Patents
Copyrights
Trademarks
Trade secrets
Data from clinical trials
Some manufactures declared pharmaceuticals as ordinary chemicals
China is a major source of harmful pharmaceuticals
In July 2014 China announced commitment to stricter regulatory control of bulk APIs
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IPR VIOLATIONS IN CHINA
Patents
Copyrights
Trademarks
Trade secrets
Data from clinical trials
Some manufactures declared pharmaceuticals as ordinary chemicals
China is a major source of harmful pharmaceuticals
In July 2014 China announced commitment to stricter regulatory control of bulk APIs
Pressure to transfer IPR to a Chinese entity
Declared intention: To promote indigenous innovation
Develop strategic industries
Pressure methods: Eligibility to subsidies, tax preferences
Deny or delay market access
Effective remedies insufficient
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ECONOMIC ESPIONAGE
Patents
Copyrights
Trademarks
Trade secrets
Data from clinical trials
The Office of the National Counterintelligence Executive (ONCIX) have reported specific gaps in trade secret protection and enforcement, particularly in China.
ONCIX: “Foreign Spies Stealing U.S. Economic Secrets in Cyberspace” states that “Chinese actors are the world’s most active and persistent perpetrators of economic espionage.”
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IPR: GRADUAL IMPROVEMENT
Patents
Copyrights
Trademarks
Trade secrets
Data from clinical trials
• 2011: China completed its Special Intellectual Property Rights Campaign
• National Leading Group on IPR infringement
• 2014: Revised Trademark Law
• 2015: amendments to the Patent Law
• AUCL – Anti-Unfair Competition Law proceeding very slowly (since 1993)
• Special IP courts launched as a pilot program
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GOOD SUPPLY PRACTICES 2013
I: General provisions
II: Quality Management for Wholesalers
• Quality Management System, Organization and Responsibility, Personnel Training, System Document, Facilities and Equipment, Calibration, Validation, Computer Systems, Procurement, Receiving, Acceptance, Storage, Transportation, Delivery, Sales
III: Quality Management for Retail of Pharmaceuticals
• Quality Management and Responsibility, Personnel, Documents, Facilities, Equipment, Purchase and Acceptance, Display and Storage, Sales and After-Sales Management
IV: Supplementary Provisions
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GOOD SUPPLY PRACTICES 2013 WHOLESALE QUALITY MANAGEMENT
QMS Organization & Responsibilities Personnel and Training QMS Documentation Facilities and Equipment Calibration and Validation Computer System
Procurement Receiving and Acceptance Storage and Maintenance Sales Delivery from Storage Transportation and Delivery After-sales Management
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GOOD SUPPLY PRACTICES 2013 RETAIL QUALITY MANAGEMENT
Quality Management and Responsibility Personnel Management Documents Facilities and Equipment Purchase and Acceptance Display and Storage Sales Management After-sales Management
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GOOD SUPPLY PRACTICES 2013 REVISED GSP GUIDELINES
Organization: R&R
Most requirements similar to ICH GDP Guidelines
Additional requirements:
Handling of traditional Chinese medicines
Ban on concurrent employment
Handling of Adverse Drug Reaction reports
Environment and personal health
Education requirements
Senior high school for most roles
Responsible Person has to be a licensed pharmacist
Specialized training for drugs under special control, refrigerated & frozen drugs
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GOOD SUPPLY PRACTICES 2013 REVISED GSP GUIDELINES
Organization: R&R
Most requirements similar to ICH GDP Guidelines
Additional requirements:
Handling of traditional Chinese medicines
Ban on concurrent employment
Handling of Adverse Drug Reaction reports
Environment and personal health
Education requirements
Senior high school for most roles
Responsible Person has to be a licensed pharmacist
Specialized training for drugs under special control, refrigerated & frozen drugs
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GOOD SUPPLY PRACTICES 2013 Article 62 and 64 documents
Business documents required from suppliers
QA agreement: • Responsibilities of both parties • Detailed specifications of materials traded • Conditions of storage and transport • Responsibility for quality assurance
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GOOD SUPPLY PRACTICES 2013
Display of medicinal products
Display of drugs Rx and OTC separately
Rx drugs cannot be on an open shelf
Dangerous drugs cannot be displayed
Provisions on Sanctions Pharmaceutical Administration Law
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RUSSIAN PHARMACEUTICAL SECTOR
2013: Emerging market, significant investment from pharma sector
After 2014: Significant slowdown due to Western sanctions
Prices regulated for 608 drugs
Russia dependent on pharmaceutical imports
• 80% drugs imported as finished products
• 20% manufactured from imported APIs
EY survey: 70% of those surveyed assert that the
current political and economic situation and
the imposition of sanctions have had no
impact on their business.
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RUSSIA: MARKET ACCESS
Building local manufacturing capabilities Partnership with Russian companies
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RUSSIA: LOCALIZATION
53% 26%
21% complete-cycle manufacturing inRussia
buy existing facilities or organize jointventures
modernize own production bases
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RUSSIA: COUNTERFEIT PHARMACEUTICALS
• Priority Watch List in 2015
• IPR protection and enforcement, notably copyright infringement and trademark counterfeiting
• Lack of enforcement
• Online pharmacies a major problem
• WTO Working Party Report: unauthorized disclosure of proprietary test data
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RUSSIA: Act No. 429-FZ of 12/2014
Federal Law on amendment of the Federal Law On Circulation of Pharmaceuticals No. 429-FZ
• Amendments to No 61-FZ of 2010
• Criminalized pharmaceutical counterfeiting and distribution of fake and adulterated pharmaceuticals
• Requirement to conform to GMP since January 2014
• New definitions: biological MPs, immune-biologic MPs, biotech MPs, gene-therapy MPs, orphan drugs, homeopathic products, reference medicinal product
• Clinical trials separated from registrations
• New grounds for cancellation of registration
• Interchangeability of pharmaceuticals
• Registration obligation on MAH
• Pricing and reimbursement for essential medicines
• Cease and desist order for illegal pharmacies
• Reference medicinal product
• Clarified powers of federal authorities
• Fast track for first three
• Procedure for determining interchangeability
• Parameters for comparison
• Bioequivalence studies not required for products that have been on the market for > 20 years
• Russian national registry
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RUSSIA: Act 429-FZ of 12/2014
• Reference medicinal product
• Clarified powers of federal authorities
• Fast track for first three
• Procedure for determining interchangeability
• Parameters for comparison
• Bioequivalence studies not required for products that have been on the market for > 20 years
• Russian national registry
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RUSSIA: Good Distribution Practice
Good Distribution Practice
Good Practice of Storage and Transportation
GMP is a licensing requirement since 2014
GMP compliance not formally confirmed
• Counterfeit and adulterated products undetectable
• GMP certificates since July 2015
• Adulterated and counterfeit drugs undetectable
Amendments must be specified in government decrees
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