Reference documentation and drugs production according GMP. Material balance. Lecture 1
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Reference documentation and Reference documentation and drugs production according drugs production according GMP. GMP. Material balance. Material balance. Lecture 1 Lecture 1
Reference documentation and drugs production according GMP. Material balance. Lecture 1
Reference documentation and drugs production according GMP.
Material balance. Lecture 1
Slide 2
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.
Slide 3
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.
Slide 4
Features of Industrial drugs technology: 1. It is characterized
by a high degree of development, as wide use machines, devices,
mechanized and automated lines lays in its basis. 2. 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.
Slide 5
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.
Slide 6
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.
Slide 7
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.
Slide 8
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.
Slide 9
State registration of medicines - a procedure that is performed
in accordance with current legislation in order to approve medical
use of medicines.
Slide 10
The Common Technical Document (CTD) 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).
Slide 11
The Common Technical Document is divided into five modules: 1.
Administrative and prescribing information 2. Overview and summary
of modules 3 to 5 3. Quality (pharmaceutical documentation) 4.
Safety (toxicology studies) 5. Efficacy (clinical studies)
Slide 12
Documents for state registration of the medicines 1. Statement
2. CTD 3. Proof of payment for registration fee
Slide 13
Information which is present in statement Name and address of
manufacturer Dosage Name (and trade name) of medicines Conditions
of release Name of active substance and its synonyms Methods of
application Dosage formTerm and storage conditions Full composition
of preparation Information about packing Medical evidence and
Contraindications Data about registration in other countries
Slide 14
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.
Slide 15
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.
Slide 16
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.
Slide 17
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. Production process of
pharmaceuticals is guided by production rules - the manufacturing
and technical ones.
Slide 18
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.
Slide 19
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.
Slide 20
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: m raw materials = m finish
product + m losses
Slide 21
InputOutput Name of starting materials & intermediates
Amount, kg Name of medicines & waste materials and losses
Amount, kg Paracetamol200,00Tablets of Paracetamol1200,0
Lactose389,48Losses, including: Starch707,00Paracetamol50 Magnium
stearat32,50Lactose30 Aerosyl10,00Starch15 Magnium stearat 13
Aerosyl12 Total:1339,00Total:1339,00 Tables of Material
balance
Slide 22
Several parameters are used for characterization of
technological process, which are calculated from material balance:
1. output of product ( ,%) 2. losses ( ,%) 3. factor of account (or
input-output characteristic - K) - Fa
Slide 23
Formulas for parameters of material balance 1. Output of
product ( ,%) - product yield = (m fp /m rm) *100 % 2. Production
loss ( ,%) = (m l /m rm)* 100 % 3. Factor of account ( consumption
factor ) Fa = (m rm /m fp)
Slide 24
Technological flowchart Process flowsheet (flowchart) - a
sequence and description of all stages in manufacturing of a
product.
Slide 25
A flowchart is 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.
Slide 26
Flowcharts are used in designing and documenting complex
processes. 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.
Slide 27
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.
Slide 28
Common alternate names include: 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.
Slide 29
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.
Slide 30
Slide 31
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.