Transcript General principles of industrial technological of medicines. Structure

Lecture 1
Reference documentation and
drugs production according GMP.
Material balance.
Plan
1. Feature of Industrial drugs technology.
2. Some aspects of creation and registration
of medicines.
3. Reference documentation.
4. Structure of chemical-pharmaceutical
enterprises.
5. Material balance.
DRUGS TECHNOLOGY
is one of the basic disciplines of
pharmaceutical education, which main
task is study of the theoretical bases of
manufacturing processing of drugs
formulation, their standardizing, storage
and release.
Features of Industrial drugs
technology:
1.
2.
It is characterized by a high degree of
development, as wide use machines, devices,
mechanized and automated lines lays in its
basis.
The work of the industrial enterprise is
characterized by a strict regulation and
planning of manufacture, as the processing of
big amount of a material is carried out.
Good Manufacturing Practices
The Current Good Manufacturing Practice
(cGMP)
regulations
for
finished
pharmaceuticals that have been promulgated
by the EU.
GMPs were intended to establish minimum
manufacturing and control practices for the
pharmaceutical industry and focus on what
needed to be done rather than how it should
be done.
GMP
requires that the buildings and facilities
are adequate, provide specifically
defined areas for certain operations
and are designed to prevent mix-ups.
Included are design and construction
features; lighting; ventilation, air
filtration, air heating and cooling;
plumbing;
sewage
and
refuse
disposal; washing and toilet facilities;
sanitation; and maintenance.
GMP
addresses equipment design, size, and
location, as well as construction,
cleaning and maintenance.
Similar to the requirements for buildings
and facilities, it is necessary to provide
appropriate
equipment
for
the
manufacture of a product and ensure
that the equipment material of
construction is not reactive, additive,
or absorptive.
Registration of pharmaceutical
preparations
1.
Chemical-pharmaceutical company can produce
medicine only after its state registration.
2.
For registration the medicines manufacturer has
got to submit the set of documents to the State
Pharmacological Center.
3.
Ministry of Health provides state registration of
medicines on the basis of examination of
registrations documents, which is submitted to the
State Pharmacological Center.
4.
Ministry of Health gives permission in the form
of registration certificate on the 5 year.
State registration of medicines
- a procedure that is performed in
accordance with current legislation in
order to approve medical use of
medicines.
The Common Technical
Document (CTD)
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is a set of specification for application dossier for
the registration of Medicines and designed to be
used across Europe, Japan and the United States.
It was developed by the European Medicines
Agency (Europe), the Food and Drug Administration
and the Ministry of Health, Labour and Welfare
(Japan).
The CTD is maintained by the International
Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals
for Human Use (ICH).
The Common Technical
Document is divided into five
modules:
1.
2.
3.
4.
5.
Administrative and prescribing information
Overview and summary of modules 3 to 5
Quality (pharmaceutical documentation)
Safety (toxicology studies)
Efficacy (clinical studies)
Documents for state registration of
the medicines
1.
Statement
2.
CTD
3.
Proof of payment for
registration fee
Information which is present in
statement
Name and address of
manufacturer
Name (and trade name) of
medicines
Name of active substance
and its synonyms
Dosage form
Full composition of
preparation
Medical evidence and
Dosage
Conditions of release
Methods of
application
Term and storage
conditions
Information about
packing
Data about
Reference documentation is
any document establishing rules, general
principles or characteristics concerning
different kinds of activity or its results.
They should provide quality and efficiency of
medical products on the basis of science and
technology advances.
There are uniform requirements for design,
order of development, coordination and
establishing of the reference documents for
pharmaceuticals, medical goods, veterinary
production and nutrients manufactured on
chemical and pharmaceutical enterprises.
The reference documents are subdivided
into the following categories:
1. Manufacturing and technical rules;
2. State pharmacopoeia (SF);
3. Monographs;
4. Analytical reference documentation (ARD);
5. State standards (StSt);
6. Branch standards (BST);
7. Specifications;
8. Guideline documents - manuals, methodical
instructions, etc.;
9. Operating instructions.
Monograph or Analytical
reference documentation
is a reference document establishing the
requirements for quality monitoring of a
drug product, its packing, storage
conditions and shelf-life.
Monographs or ARD are adopted for any
pharmaceutical or crude drug, allowed for
medical use and industrial manufacturing by
Ministry of Health.
Production process of
pharmaceuticals is guided by
production rules - the manufacturing
and technical ones.
Manufacturing rules - the reference
document describing the consequence of all
operating procedures and used equipment,
establishing all manufacturing parameters
and sites of quality monitoring and
containing specifications on starting
materials, intermediates and final products.
The sections of MR :
1. The characteristic of a finished product.
2. Manufacturing flowchart and operation process:
• The flowchart of manufacture;
• The characteristics of starting material, materials and
intermediates;
• The description of operation stages;
• Material balance.
3. In-process control.
4. Appendices:
• The list of technological instructions.
• The list of report blanks.
Technical rules
represent the reference document establishing the conditions
providing an appropriate quality of medical products with respect
to a particular complex of the process equipment.
Technical rules cover preparing of laboratory, pilot and
manufacturing premises and the personnel for work;
 sanitary-and-hygienic conditioning of manufacture;
 the requirements for occupational safety,
 safety precautions,
 fire safety,
 environment control;
 equipment operation etc.
Requirements of the given rules guarantee quality of released
production, rational carrying out of technical processes,
preservation of the equipment, exception of an opportunity of
occurrence of failures and environmental contaminations.
Material balance (mass balance) is a ratio
between starting materials and obtained ones
as the result of manufacturing process.
It allows to compare theoretically possible and
actual yields of final goods.
In absence of rejects and by-products the
material balance equation is simplified as:
mraw materials= mfinish product + mlosses
Tables of Material balance
Input
Output
Name of starting
materials &
intermediates
Amount,
kg
Name of medicines &
waste materials and
losses
Paracetamol
200,00
Tablets of Paracetamol
Lactose
389,48
Losses, including:
Starch
707,00
Paracetamol
50
Magnium stearat
32,50
Lactose
30
Aerosyl
10,00
Starch
15
Magnium stearat
13
Aerosyl
12
Total:
1339,00
Total:
1339,00
Amount,
kg
1200,0
Several parameters are used for
characterization of technological process,
which are calculated from material
balance:
1.
2.
3.
output of product (,%)
losses (,%)
factor of account (or input-output
characteristic - K) - Fa
Formulas for parameters of
material balance
1. Output of product (,%) - product yield
η = (mfp/mrm)*100 %
2. Production loss (,%)
ε = (ml/mrm)*100 %
3. Factor of account (consumption factor )
Fa = (mrm /mfp)
Technological flowchart
Process flowsheet
(flowchart) - a sequence
and description of all
stages in manufacturing
of a product.
A flowchart is
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a type of diagram that represents an algorithm or
process, showing the steps as boxes of various
kinds, and their order by connecting these with
arrows;
This diagrammatic representation can give a
step-by-step solution to a given problem;
Data flows are not typically represented in a
flowchart, in contrast with data flow diagrams;
rather, they are implied by the sequencing of
operations.
Flowcharts are used in designing and
documenting complex processes.
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Like other types of diagram, they help
visualize what is going on and thereby
help the viewer to understand a process,
and perhaps also find flaws.
Flowcharts are used in analyzing,
designing, documenting or managing a
process or program in various fields.
The two most common types of boxes in
a flowchart are:
a processing step, usually called
activity, and denoted as a rectangular
box;
a decision, usually denoted as a
diamond.
Common alternate names include:
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flowchart,
process flowchart,
functional flowchart,
process map,
process chart,
functional process chart,
business process model,
process model,
process flow diagram,
work flow diagram,
business flow diagram.
Technological flowchart is the visual
display of dosage production.
Technological
flowchart (Process
flowsheet) - a sequence
and description of all
stages in manufacturing
of a product.
Arrows
Showing "flow of control".
An arrow coming from one symbol
and ending at another symbol
represents that control passes to
the symbol the arrow points to.
Thank you for your
attention