Introduction
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Lukáš Dvořák - Working experiences
• 2006 - 2007 UP Olomouc, Faculty of Science, Department
of Inorganic Chemistry – Scientific Researcher
• 10/2009 – 12/2010 Teva Czech Industries s.r.o. – Quality Control
Specialist
• 01/2011 – 09/2011 Teva Czech Industries s.r.o. – Incoming Control
Laboratory Supervisor
• 10/2011 - 05/2015 - Teva Czech Industries s.r.o. – Head of TSA QC
dept. (Technical and Scientific Affairs)
• 06/2015 – 04/2017 - Teva Czech Industries s.r.o. – TSA Manager
(Production Technologies)
• 05/2017 - 03/2018 – Favea a.s. - Qualified Person – control and
certification of human or veterinal products; investigation, batch
documentation control
• 04/2018 till now – Favea a.s. – QC Senior Specialist & Qualified
Person
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Extrawork
• 01/2016 till now – external expert supporting
GMP area in Czech Accreditation Institute
• 09/2017 till now QDP supervisor in two shipper
companies
• 01/2018 till now – Parliament of the Czech
republic – consultant (healthy committee of the
Chamber of Deputies)
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Additional education & courses
• 2015 Teva Early Talent Programme
• 2014 Course for Qualified Person of
Manufacturers of medicinbal Products to be in
accordance with Czech National Law 378/2007
• 2011 Validation manager courses
(presented by IIR)
• 2011 Competent leadership (presented by
AHRA – 8 days module: Key Manager
Competencies, Leadership, Change Control,
Creativity)
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Work-life balance
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ICH (International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceutical for Human
Use - Quality
• Q1 Stability Issue
• Q2 Validation issue
• Q3 Impurities
• Q4 Pharmacopoeias
• Q5 Quality of Biotechnological Products
• Q6 Specifications
• Q7 GMP for API
• Q8 Pharmaceutical Development
• Q9 Pharmaceutical Risk Management
• Q10 Pharmaceutical Quality Systém
• Q11 Development and Manufacture of DS
• Q12 Lifecycle Management
ICH Q7 general chapters
• There should be an adequate number of personnel
qualified by appropriate education, training and/or
experience to perform and supervise the manufacture
of intermediates and APIs
• The responsibilities of all personnel engaged in the
manufacture of intermediates and APIs should be
specified in writing
• Training should be regularly conducted by qualified
individuals and should cover, at a minimum, the
particular operations that the employee performs and
GMP as it relates to the employee's functions. Records
of training should be maintained. Training should be
periodically assessed.
• Personnel should avoid direct contact with
intermediates or APIs.
• Personnel should wear clean clothing suitable for
the manufacturing activity with which they are
involved and this clothing should be changed
when appropriate. Additional protective apparel,
such as head, face, hand, and arm coverings,
should be worn when necessary, to protect
intermediates and APIs from contamination.
• Consultants advising on the manufacture and
control of intermediates or APIs should have
sufficient education, training, and experience,
or any combination thereof
• Records should be maintained stating the
name, address, qualifications, and type of
service provided by these consultants
• Equipment used in the manufacture of intermediates
and APIs should be of appropriate design and adequate
size.
• Suitably located for its intended use, cleaning,
sanitization (where appropriate), and maintenance.
• Production equipment should only be used within its
qualified operating range.
• Closed or contained equipment should be used
whenever appropriate.
• Written procedures should be established for cleaning
of equipment and its subsequent release for use in the
manufacture of intermediates and APIs.
• Equipment and utensils should be cleaned, stored, and,
where appropriate, sanitized or sterilized to prevent
contamination or carry-over of a material.
• Where equipment is assigned to continuous
production or campaign production of successive
batches of the same intermediate or API, equipment
should be cleaned at appropriate intervals to prevent
build-up and carry-over of contaminants.
• Non-dedicated equipment should be cleaned between
production of different materials to prevent cross-
contamination.
• The company's overall policy, intentions, and
approach to validation, including the validation of
production processes, cleaning procedures,
analytical methods, in-process control test
procedures, computerized systems, and persons
responsible for design, review, approval and
documentation of each validation phase, should
be documented.
• The critical parameters/attributes should
normally be identified during the development
stage or from historical data, and the ranges
necessary for the reproducible operation should
be defined.
Process Design Process Qualification
Continued Process
Verification
Define
•Critical Process
parameters set up
•Critical Quality
Atributes set up
Design
Space
•Ranges
•Limits
Support
•ICH Q11
•EudraLex, Volume 4,
Annex 15
•FDA Guid. For Industry:
Process Validation
Define
•CQA & CPP evaluation under
actual conditions of use
•Scale up, commercial scale
•Specification
Methodology
•Validated analytical methods
•Impurity profile
•Cleaning validation
•Hold time studies
Support
•ICH Q2(R1)
•EudraLex, Volume 4, Annex
15
•FDA Guid. For Industry:
Analytical Procedures and
Methods Validation for Drugs
Control
• Continued
monitoring
• On-going stability
programme
Correlation
& Action
• Cp, cpk indexes
• Trend analysis
• CAPA system
Support
• ICH Q9
• FDA Guid. For
Industry: Process
Validation
DOCUMENTATION ON EACH STEP OF VALIDATION
Validation - Qualification
Take home message
Elemental Impurities - history
25.4. 2018
Lukáš Dvořák
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Simon Sinek – Golden Circle
PROČ?
JAK – ICH Q3D
CO – změna legislativy
Colour of Sulfites
• Over 100 years old (circa 1905)
• Semi-quantitative method based on color reaction
• Very low sensitivity
• Non-specific for individual metals
• Some metals cannot be tested (Pd, Pt, Ni, V)
• Not accurate for volatile elements (Hg, Sb, Se, Pb)
“Although still widely accepted and used in the pharmaceutical industry, these
methods based on the intensity of the color of sulfide precipitation are non-specific,
insensitive, time-consuming, labor intensive, and more often than hoped, yield low
recoveries or no recoveries at all.”
Ref.: Wang, T. et al, J. Pharm. & Biomed. Anal., Vol. 23 (2000) 867-890)
Schott hot plate and beaker explosion -
photodocumentation
Calcium Stearate NF:
Zákon o léčivech 378/2007
§33 (1)
Držitel rozhodnutí o registraci musí provádět
veškeré změny potřebné k tomu, aby bylo
možné léčivý přípravek vyrábět a kontrolovat
obecně uznávanými vědeckými metodami.
ICH (International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceutical for Human
Use - Quality
• Q1 Stability Issue
• Q2 Validation issue
• Q3 Impurities:
• A) Q3A
• B) Q3B
• C) Q3C
• D) Q3D
• Q4 Pharmacopoeias
• Q5 Quality of Biotechnological Products
• Q6 Specifications
• Q6A Specifications for New DS and FP:Chemical Substances
• Q7 GMP for API
• Q8 Pharmaceutical Development
• Q10 Pharmaceutical Risk Management
• Q11 Development and Manufacture of DS
• Q12 Lifecycle Management
Elemental Impurities - Guidelines change
Step 4
Effective
Dec 2015 (?) 2018
ICH
Q3D
USP
Ph.Eur
5.20
2.4.20
Current
Heavy metals
