POSSIBILIDADES CONCRETAS DE ABSORO DE PSGRADUADOS NO BRASIL

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POSSIBILIDADES CONCRETAS DE ABSORÇÃO DE
PÓS-GRADUADOS NO BRASIL

• jrabi_at_microbiologica.ind.br

Curitiba, 25 de Novembro de 2005
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•  A science-based Brazilian Company with its core
  competence focused on nucleoside process
  chemistry.
• It was founded in 1981 by a group of scientists
  from the Federal University of Rio de Janeiro.

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• A learning organization which is continuously
  reinventing itself through the discipline of
  Scientific Research, Development, and
  Manufacture.
• This provides a natural way of furthering our
  education and training, the advancement of our
  infrastructure, the continuous upgrade of our
  procedures and documentations, and the build up
  of a truly cohesive, flexible, and efficient
  institution.

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• Conhecimento é o fator principal na criação de
  riqueza, cuja dinâmica é fundamentada na relação
  íntima entre
• ideas informação
• dinheiro
  

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• Entretanto, continuaremos sempre a vender e
  comprar objetos materiais. A indústria representa
  a eficácia que transforma o conhecimento em
  produtos.
• Para produzir esses objetos e necessário
  integrar competências, colaboradores,
  fornecedores, parceiros, etc., de forma
  organizadamente documentada. No caso dos APIs,
  esta documentação se denomina DMF que deve ser
  submetida a agência regulatória.
• Assim, a industria trabalha
• para dar vida as ideas.

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• Process Research Development
• Quality Assurance
• Manufacturing
• Marketing

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Process Research Development
New Project Approach

• Best route is selected
• Technology is refined
• Preparation of inter-mediates and impurities for
  analytical studies

• Length/Yield/Purification/Efluents
• Group integration
• Using small-scale techniques

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Process Research Development
New Project Approach
Development of analytical methods Process
scale-up - Manufacture and Documentation
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Process Research Development
Documentation

• Paper Lab Notebooks
• E-notebooks
• Analysis Request Log Book
• Analysis Request Form

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Process Research Development
Example of E-Lab Notebook
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Process Research Development
Analysis Request Form
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Process Research Development
Documentation

• Elaboration of Manufacturing Prescription (MAP)
• Product and intermediate Specifications
• Working towards implementing the same approach as
  used by the Quality Assurance Group for product
  certification.

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Core Competence

• Nucleoside Chemistry
• Process Research Development
• Quality Assurance
• Manufacturing
• Marketing

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STEPS FOR PRODUCT CERTIFICATION
Raw and Auxiliary materials analysis
Production Process
Final Product
Raw and auxiliary materials acquisition
Product File Review
EMISSION OF THE CERTIFICATE OF ANALYSIS
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Production Process
Raw and auxiliary materials acquisition
Raw and Auxiliary materials analysis
Final Product
Product File Review
RAW AND AUXILIARY MATERIALS ANALYSIS

• Raw and Auxiliary Materials are sampled for
  analysis and retention samples, as directed by
• SOP CQ-Q-0024 Sampling Procedures for Raw,
  Secondary Materials, and Intermediates for
  Analysis
• SOP CQ-Q-072 Retention Samples Organization
  and Maintenance Procedures
• Materials are analyzed according to written
  specifications and analysis prescriptions, as
  directed by SOP DG-G-006 Elaboration of
  Analysis Prescriptions and Specifications.
• Approved materials have their yellow quarantine
  labels substituted by green approved ones, as
  directed by
• SOP DG-G-009 Inspection and Testing Situation
• Non-conforming materials receive a pink label as
  directed by the a.m. SOP, and are treated as
  directed by
• SOP DG-G-007 Non-conforming Products Control
• Once approved, materials are released for use in
  production process. If stored, are periodically
  retested according to
• SOP CQ-Q-063 Materials Retest Date

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Production Process
Raw and auxiliary materials acquisition
Final Product
Raw and Auxiliary materials analysis
Product File Review
PRODUCTION PROCESS

• Production batches are produced according to
  written Manufacturing Procedures (MAPs), which
  are standardized as described under
• SOP DG-G-005 Manufacturing Procedures (MAPs)
  Elaboration
• Process data are registered into batch records,
  which are attachments to the respective MAPs, and
  contain information of step by step procedures,
  critical steps, IPEs, sampling and conversion
  calculations
• In-process controls (IPC) performed as directed
  in each individual MAP. When necessary,
  specifications and analysis prescriptions are
  elaborated to describe specific limits to be
  achieved and respective testing methodology

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EXAMPLE OF MANUFACTURING INSTRUCTION
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Production Process
Raw and auxiliary materials acquisition
Final Product
Raw and Auxiliary materials analysis
Product File Review
Each Equipment used in the production process
follows a chronogram of preventive maintenance,
like the example below.
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Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
FINAL PRODUCT

• Final Product is sampled and analyzed according
  to written specifications and analysis
  prescriptions, which are based on current
  Pharmacopoeias
• SOP CQ-Q-083 Final Product Sampling
• SOP DG-G-006 Elaboration of Analysis
  Prescriptions and Specifications
• Approved products, after Product File Review, are
  labeled with final label, according to written
  procedures, and non-conforming products are duly
  identified as such, and treated as directed by
  written SOP
• SOP CQ-S-066 Identification Labels of Certified
  Final Product
• SOP DG-G-007 Non-conforming Products Control
• Shelf life of Final Products is determined based
  on stability studies, according to written
  procedures, under both accelerated (402oC/755
  RH) and field (252oC/605 RH) conditions
• SOP DG-G-045 Final Products Stability Testing
  Program

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EXAMPLE OF FINAL PRODUCT SPECIFICATION
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Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
FINAL PRODUCT

• Example of stability studies being performed for
  the determination of shelf life and to provide
  the basis
• for revalidation as necessary (Revalidation is
  described by SOP DG-G-004 Product Revalidation)

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Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
FINAL PRODUCT

• Tendency analysis of tests results are performed
  to optimize the final product specifications

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Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
PRODUCT FILE REVIEW

• At the end of a product campaign, the Failure
  Reports provide a powerful tool to refine the
  manufacturing process. Based on the analysis of
  the failures reported, the Quality Assurance
  Department can determine if
• additional training is required,
• the manufacturing instructions must be
  revised,
• the product must be maintained in
  quarantine for evaluation due to any process
  deviation.

If all items verified in the Product File Review
are in conformance to predefined standards, the
final product is approved and a Certificate of
Analysis issued by Quality Assurance Department.
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GMP Tools
Microbiologicas GMP system is supported by the
following SOPs

• DG-G-001 Standard Operating Procedures (SOPs)
  Elaboration
• DG-G-002 Document changing
• DG-G-003 Approval, circulation and distribution
  of Documents
• DG-G-005 Elaboration of Manufacturing Procedures
  (MAPs)
• DG-G-006 Elaboration of Specification and
  Analytical Prescriptions
• DG-G-007 Non-conforming Products Control
• DG-G-008 Corrective / Preventive Action
• DG-G-009 Inspection and Testing Situation
• DG-G-010 Return and Recall of Products
• DG-G-011 Process Validation Procedure.

The above mentioned SOPs are General Guidelines
directing the GMP conduction in the Company.
Based on these SOPs, all other procedures
performed by every Department of the Company are
base on specific written Standard Operation
Procedures (SOP)
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GMP Tools
The GMP System is frequently tested for
compliance with current regulations by means of
the following powerful tools
PRODUCT ANNUAL REVIEW
QUALITY AUDITS
and

• Product annual review includes revision,
  annually, for each product, of
• Batch records (SOP DG-F-046 Product File
  Review)
• Failure reports (SOP DG-F-046)
• Complaint, recalls and devolution files (SOP
  DG-G-108 Customer Complaints, and SOP DG-G-010
  Devolution, Return and Recal)
• Non-conformities files (SOP DG-G-007
  Non-conforming Product Control)
• Discrepancy failures to meet specifications
  (Tendency Analysis)
• Conclusions are made based on the a.m.
  investigations, and registered regarding the need
  for product changes.

• Quality / GMP audits are performed, according to
  SOP CQ-G-049 Internal Audits, and are basically
  of 4 types
• Internal Audit
• Third Part Audit
• Supplier Audit
• Product Audit
• Conclusions are made based on the observations
  during the Audit Program, and follow-up for
  corrective actions is performed.

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Core Competence

• Nucleoside Chemistry
• Process Research Development
• Quality Assurance
• Manufacturing
• Marketing

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ORGANIZATIONAL STRUCTURE
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Jacarepagua Site
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EXAMPLE OF MANUFACTURING PRESCRIPTION (MAP)
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EXAMPLE OF MANUFACTURING INSTRUCTION
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Production Process
Raw and auxiliary materials acquisition
Final Product
Raw and Auxiliary materials analysis
Product File Review
Each Equipment used in the production process
follows a chronogram of preventive maintenance,
like the example below.
32
Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
FINAL PRODUCT

• Final Product is sampled and analyzed according
  to written specifications and analysis
  prescriptions, which are based on current
  Pharmacopoeias
• SOP CQ-Q-083 Final Product Sampling
• SOP DG-G-006 Elaboration of Analysis
  Prescriptions and Specifications
• Approved products, after Product File Review, are
  labeled with final label, according to written
  procedures, and non-conforming products are duly
  identified as such, and treated as directed by
  written SOP
• SOP CQ-S-066 Identification Labels of Certified
  Final Product
• SOP DG-G-007 Non-conforming Products Control
• Shelf life of Final Products is determined based
  on stability studies, according to written
  procedures, under both accelerated (402oC/755
  RH) and field (252oC/605 RH) conditions
• SOP DG-G-045 Final Products Stability Testing
  Program

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EXAMPLE OF FINAL PRODUCT SPECIFICATION
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EXAMPLE OF FINAL PRODUCT ANALYSIS PRESCRIPTION
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Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
FINAL PRODUCT

• Tendency analysis of tests results are performed
  to optimize the final product specifications

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Raw and auxiliary materials acquisition
Production Process
Final Product
Raw and Auxiliary materials analysis
Product File Review
PRODUCT FILE REVIEW

• At the end of a product campaign, the Failure
  Reports provide a powerful tool to refine the
  manufacturing process. Based on the analysis of
  the failures reported, the Quality Assurance
  Department can determine if
• additional training is required,
• the manufacturing instructions must be
  revised,
• the product must be maintained in
  quarantine for evaluation due to any process
  deviation.

If all items verified in the Product File Review
are in conformance to predefined standards, the
final product is approved and a Certificate of
Analysis issued by Quality Assurance Department.
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Cadeia de agregação de Valor

• Interdisciplinaridade
• GMP
• Regulação
• Tecnologias mais limpas
• Canais de distribuição
• Conhecimento intensivo
• Especificidade
• Poder alavancador das inovações.
• Patente de USO
• Privilégio de mercado

• Intermediários básicos, 1-5 USD/Kg
• Intermediários sintéticos aquirais, 10-50USD/Kg
• Intermediários quirais, 50-gt1000USD/Kg
• APIs, 50-1000USD/Kg
• 
  
• ADP APIs x 10-100!!!