GMP, GLP

1
GMP, GLP ??????????? ???????????1963 ?.
????????? ?? ??????? GMP1970 ?. FDA ?????? ?
?????? ?? ???????? ??????? ?? ?????????? ??
??????????? ? ???????? ????????? ????????
?????? ??????? ?? ???? ?? ???????? ???????
????? ?? ???????? ?? ??????? ?? ??????????19
??????? 1976 ?. GLP ?????????1994 ?. ICH
(International Conference on Harmonization)
??????? ???????????? ?????????? ? ??????????? ??
?????????? ? ??????????? ?? ????????? ?? ???????
????????1996 ?. FDA ??????? ?????????? ??
????????? ? ?? ?? ????????? ? ????????????
?????????? ?? ??????????????? ????????????
2
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3
Since its first publication in 1971 this text,
commonly known as the Orange Guide, has been an
essential reference for all involved in the
manufacture or distribution of medicines in
Europe. It is of particular relevance to all
holders of manufacturer's licences and wholesale
dealer's licences and to their Qualified Persons
and Responsible Persons, who have a
responsibility for ensuring compliance with the
regulatory requirements. The Orange Guide
collates in one convenient, up-to-date and
authoritative source European and UK guidance
documents and information on legislation relating
to the manufacture and distribution of medicines
for human use. Changes to this edition
include Detailed changes to the EU guide to good
manufacturing practice Detailed revisions to the
EU Directive on medicinal products for human use
The new Directive on the Principles and
Guidelines on Good Manufacturing Practice of
Medicinal Products for Human Use Compiled by the
Inspection and Standards Division, Medicines and
Healthcare products Regulatory Agency (MHRA),
London, UK.
4
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5
????????? ?? EMEA
6

• European Medicines Agency
• The European Medicines Agency (EMEA) is a
  decentralised body of the European Union with
  headquarters in London.
• Its main responsibility is the protection and
  promotion of public and animal health, through
  the evaluation and supervision of medicines for
  human and veterinary use.
• The EMEA is responsible for the scientific
  evaluation of applications for European marketing
  authorisation for medicinal products (centralised
  procedure). Under the centralised procedure,
  companies submit one single marketing
  authorisation application to the EMEA.
• All medicinal products for human and animal use
  derived from biotechnology and other
  high-technology processes must be approved via
  the centralised procedure. The same applies to
  all human medicines intended for the treatment of
  HIV/AIDS, cancer, diabetes or neurodegenerative
  diseases and for all designated orphan medicines
  intended for the treatment of rare diseases.
  Similarly, all veterinary medicines intended for
  use as performance enhancers in order to promote
  the growth of treated animals or to increase
  yields from treated animals have to go through
  the centralised procedure.
• For medicinal products that do not fall under any
  of the above-mentioned categories companies can
  submit an application for a centralised marketing
  authorisation to the EMEA, provided the medicinal
  product constitutes a significant therapeutic,
  scientific or technical innovation or the product
  is in any other respect in the interest of
  patient or animal health.

7

• The safety of medicines is monitored constantly
  by the Agency through a pharmacovigilance
  network. The EMEA takes appropriate actions if
  adverse drug reaction reports suggest changes to
  the benefit-risk balance of a medicinal product.
  For veterinary medicinal products the Agency has
  the responsibility to establish safe limits for
  medicinal residues in food of animal origin.
• The Agency also has a role to stimulate
  innovation and research in the pharmaceutical
  sector. The EMEA gives scientific advice and
  protocol assistance to companies for the
  development of new medicinal products. It
  publishes guidelines on quality, safety and
  efficacy testing requirements. A dedicated office
  established in 2005 provides special assistance
  to small and medium-sized enterprises (SMEs).
• In 2001, the Committee for Orphan Medicinal
  Products (COMP) was established, charged with
  reviewing designation applications from persons
  or companies who intend to develop medicines for
  rare diseases (so-called orphan drugs). The
  Committee on Herbal Medicinal Products (HMPC) was
  established in 2004 and provides scientific
  opinions on traditional herbal medicines.

8

• The Agency brings together the scientific
  resources of over 40 national competent
  authorities in 30 EU and EEA-EFTA countries in a
  network of over 3,500 European experts. It
  contributes to the European Unions international
  activities through its work with the European
  Pharmacopoeia, the World Health Organization, and
  the ICH and VICH trilateral (EU, Japan and US)
  conferences on harmonisation, among other
  international organisations and initiatives.
• The EMEA is headed by the Executive Director and
  has a secretariat of about 500 staff members in
  2008. The Management Board is the supervisory
  body of the EMEA, responsible, in particular, for
  budgetary matters.
• The Agency is also involved in referral
  procedures relating to medicinal products that
  are approved or under consideration by Member
  States

9
European Pharmacopoeia (Ph. Eur.)Legal basisThe
legal basis for the European Pharmacopoeia is the
Council of Europe Convention on the elaboration
of a European Pharmacopoeia, an international
treaty signed initially by 8 member states.
Currently 37 countries have acceded to the
Convention as individual states and the European
Community has also acceded as a supranational
body. Other countries (European and non-European)
are observers.PreparationThe Ph. Eur. is
produced by the European Pharmacopoeia Commission
(EPC) located in Strasbourg, France. The
technical secretariat of the EPC is part of the
Council of Europe's European Directorate for the
Quality of Medicines and Healthcare (EDQM)
(external link)(The Council of Europe (C of E)
is an intergovernmental organisation, founded in
1949, with its headquarters in Strasbourg. The
Council of Europe has many links to, but should
not be confused with, the European Community/
European Union (EC/EU) based in Brussels. The UK
has been a member of the C of E since its
inception and was one of the eight original
signatories to the Pharmacopoeia Convention in
1964.)Current editionThe current edition of
the Ph. Eur. is the 6th edition as amended by
Supplements. The Ph. Eur. is published separately
in book form and on CD-ROM and is also available
online.ContentThe Ph Eur comprises monographs,
which set out the mandatory standards for active
substances, excipients and formulated
preparations, together with supporting General
Notices, method texts, and reagent
specifications. Unless otherwise indicated, the
monographs of the European Pharmacopoeia apply
equally to materials for use in either human or
veterinary medicine.
10
Structure of the PharmacopoeiaThe current edition of the BP is the British Pharmacopoeia 2007, which contains nearly 3,000 monographs for substances and articles used in the practice of medicine. The latest 2007 edition comprises six volumes that are comprehensively indexed and cross-referenced for easy reference

Volumes I and II Medicinal Substances
   
Volume III Formulated Preparations, Blood related Preparations, Immunological Products, Radiopharmaceutical Preparations and Surgical Materials Homoeopathic Preparations
   
Volume IV Appendices, Infrared Reference Spectra and Index
   
Volume V British Pharmacopoeia (Veterinary) 2007
   
Volume VI CD-ROM version of BP 2007, BP (Veterinary) 2007 incorporating British Approved Names
11
The BP is available as a printed volume and
electronically in both on-line and CD-ROM
versions.Both CD-ROM and web solutions use
sophisticated search techniques so that
information can be located quickly. For example,
pharmacists referring to a monograph can
immediately link to other related substances and
appendices referenced in the content by using
hypertext links within the text.Production of
the British PharmacopoeiaThe BP is prepared by
the Pharmacopoeial Secretariat working in
collaboration with the BP Laboratory, the British
Pharmacopoeia Commission (BPC) and its Expert
Advisory Groups (EAG) and Advisory Panels. The
development of pharmacopoeial standards receives
input from relevant industries, hospitals,
academia, professional bodies and governmental
sources, both within and outside the UK.The BP
Laboratory provides analytical and technical
support to the British Pharmacopoeia. Its major
functions are Development of new pharmacopoeial
monographs the laboratory undertakes the
development and validation of qualitative and
quantitative test methods for new monograph
specifications for publication in the BP and
refines and revalidates test methods for existing
BP monographs. BP Chemical Reference Substance
(BPCRS) the laboratory is responsible for the
procurement, establishment, maintenance and sale
of BPCRS. The catalogue currently contains about
500 BPCRS, which are needed as standards for
monograph tests in both the BP and the BP
(Veterinary). Information regarding BPCRS is
available on the BP Laboratory website (external
link).
12
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13
Good Manufacturing Pactices

• ????? ?????????????? ????????

14
GMP

• ??????? ?? ??????????? ?? ??????????,
  ??????????? ?? ????????????? ???????? ??
  ???????????, ?????????? ? ??????????? ????????? ?
  ???????????? ? ?????????????? ?????????.

15
GMP

• ???????, ????????? ?????? ???????, ?????
  ????????? ??? ?????????? ?? ???????????? ???????
  ???????, ?????????? ? ???????????????.

16
GMP

• ?????????, ????????? ??? ?????????????? ?
  ???????? ?? ???????????? ???????, ???????? ??
  ??????? ?? ???????? ?
• Men ????????, ???????????? ????????
• Materials ????????, ??????????, ????????,
  ???????, ???????? ? ?.?.
• Machinery ?????????, ?????????? ????????,
  ??????????
• Methods ????????????? ??????, ???????,
  ?????????, ????????????.

17
GMP ????????? ???????

• ???????????? ?? ????????? ? ??????????????
  ???????, ??????????? ?????????? ? ??????? ??
  ????????????
• ????????????? ?? ???????????????? ??????? ?
  ???????????? ???????
• ???????? ? ????????????? ?? ????????????.

18
??????????? ?? ?????????

• ???? (audit cf ISO 8402) ???????????? ?
  ?????????? ????????? ?? ?????????? ? ???????? ??
  ???????????, ???????? ? ????????????? ?????????
  ????????? ??????????.
• ??????? (batch) ?????????? ?????????? ??
  ??????? ????????, ?????????? ???????? ???
  ???????, ??????????? ? ???? ????????????? ??????
  ??? ????? ?? ???????, ????? ?? ????????????? ???
  ?????? ???????????.

19
??????????? ?? ?????????

• ???????? ????? (batch number) ???????????
  ?????????? ?? ????? ?/??? ?????, ????? ??????????
  ???????????? ????????? ????? ???????, ??????????
  ?????????, ???????????? ??????????? ? ??.
• ???????? ???????????? (batch records) ???????
  ?????? ?????????, ???????? ? ?????????????? ??
  ??????? ?? ?????????? ??? ????? ???????.

20
??????????? ?? ?????????

• ???????? ???????????? (batch records) ???????
  ?????? ?????????, ???????? ? ?????????????? ??
  ??????? ?? ?????????? ??? ????? ???????.
• ?????????? (???????) ??????? (bulk product)
  ???????, ????? ? ???????? ???? ?????? ????? ??
  ??????????????? ?????? ? ?????????? ??
  ???????????.

21
??????????? ?? ?????????

• ?????????? (components) ????? ????????, ?????
  ???????? ??????? ???????, ??????????? ???????????
  ????????.
• ????? ??????? (finished product) ??????????
  ???????, ???????? ???? ?????? ????? ??
  ??????????????? ?????? ? ? ?? ??????.

22
??????????? ?? ?????????

• ???????????? (manufacture) ?????? ????????,
  ???????? ??? ??????????? ?? ???????????? ???????
  ?? ???????????? ?? ???????????, ????
  ????????????? ?? ??? ??????????????? ?
  ??????????? ?????? ?? ???????????? ?? ???????
  ??????? ? ????????? ? ???? ???????? ???????.

23
??????????? ?? ?????????

• ????????? (procedures) ???????? ?? ??????????,
  ????? ?????? ?? ????? ?????????, ???????????
  ?????, ????? ?????? ?? ????? ?????, ????? ?
  ??????????, ????? ?????? ?? ????? ?????????
  ???????? ??? ?????????? ??? ?????????????? ??
  ???????????? ???????.

24
??????????? ?? ?????????

• ??????????? ?? ?????????? (quality assurance, cf
  ISO 8402) ??????? ?? ?????????????? ?????,
  ????? ????????? ??? ???? ???? ???????? ??????
  ??????? ?? ?????????? ? ????????????? ?? ????????
  ? ???????????? ? ????????????.
• ????????? ??????? (quality control)
  ?????????????? ?????????, ?????????, ??????? ??
  ????????? ?? ??????????? ????????.

25
??????????? ?? ?????????

• ???????? (raw material) ????? ????????
  ??????????, ????? ?? ??????? ? ??????? ??
  ?????????? ?? ??????? ???????.
• ?????? ??????? (return) ????? ???????, ????????
  ??????? ?? ?????????????.

26
??????????? ?? ?????????

• ???????????? (specification) ???????? ????????
  ?? ????????????, ?? ????? ?????? ?? ?????????
  ?????????? ??? ???????????, ???????? ???
  ?????????? ?? ????? ?? ??????????????. ????? ????
  ?????? ?? ?????? ?? ??????? ????????.
• ???????? ??????? (semi-finished product)
  ???????? ?????????? ???????, ????? ?????? ?? ??
  ??????? ?? ???????? ?????????????? ????????, ??
  ?? ????? ????? ???????.

27
?????????? ?? ??????????

• ??????? ?? ??????????? ?? ??????????, ?????????
  ???????????? ?? GMP ? ????????? ????????? ???????

28
?????????? ?? ??????????

• ????????? ??????????????, ?????????
  ???????????????? ?????????, ??????????? ????????
  ??? ??????????? ???????????? ? ?????????????
  ?????? ?? ?????? ? ??????????
• ???????? ????????, ?????????? ?? ??????????? ??
  ????????, ?? ????????? ?? ???????? ??
  ???????????? ?? ???????? - ??????????? ??
  ??????????

29
?????????? ?? ??????????

• ??????, ??????????, ??????? ?????????
  ?????????? ? ??????????, ????????? ????????????
  ?? ??????????, ???????????, ???????? ?
  ??????????.
• ????????? ???????????? ?? ????????? ?? ???????
  ?????????, ?????????? ??? ??????????? ??
  ?????????????? ???????? ? ????????????????
  ?????????

30
????? ???????? ??? ????????????

• ?????? ???????? ??? ?????????????? ?????? ??
  ????? ????? ?????????? ? ????????? ?? ??????????
  ?? GMP ? ????? ???????????? ?? ???????? ?
  ???????????? ???????? ? ? ???????????? ?
  ???????????? ?? ???????????? ? ???????????.

31
????? ???????? ??? ????????????

• ???? ???????????? ?? ??????????? ?? ???? ??????
  ?? ???? ? ???????????? ? ?????????? ?? ????,
  ?????????? ?? ?????????????? ?? ??????? ???????
  ??????? ??????? ?????? ?? ????? ?????????????? ??
  ?????????? ????????? ?? ?????? ?? ??????????
  ???? ?? ???????? ??????????? ???? ????????? ?
  ??????????????? ???????? ?? ?????? ?????? ?? ????
  ??????????? ?????????.

32
????? ???????? ??? ????????????

• ???????????? ?????????? ?? ????????? ?????????
• ???????????? ?? ???????? ????? ?????? ?????? ??
  ??????????
• ???????????? ?? ???????? ?? ?????????? ??????
  ?/??? ??????? ???
• ???? ?? ??????????
• ????? ?? ????????????? ? ?????????? ????? ?
  ???????? ?????
• ??????? ?????????? ? ???? ?? ?????????? ????????.

33
????? ???????? ??? ????????????

• ?????????? ?????? ??????? ????????, ???????? ?
  ?????? ???????? ?? ?????????? ????????? ???????
  ???????, ?? ?? ?? ?? ???????????? ???????
  ????????, ??????????? ? ???????????.

34
????? ???????? ??? ????????????

• ???????????? ?????? ??????? ?? ??????????? ??
  ??????????? ? ??????????, ????????? ??????????,
  ??????? ?? ?????, ?????????, ?????????????,
  ??????????, ???????????, ????????????, ?????????,
  ????????????? ? ??., ?????? ?? ?? ????????? ?
  ???????????? ? ??????? ?????????? ? ?? ?????
  ????????????? ??????, ?????? ? ??????????.

35
????? ???????? ??? ????????????

• ?? ?? ?? ??????? ????????, ??????????? ??
  ???????? ? ?????????, ?? ??????? ?????? ???????
  ?? ????????? ?????????????????, ??????? ??
  ??????????, ????????? ?? ?????????????? ?? ?????,
  ????????? ?????????? ? ???????.

36
????? ???????? ??? ????????????

• ??????? ? ?????????? ??????? ?? ?????
  ?????????????? ?? ?????? ??????????, ???????? ?
  ??????? ????????. ???????????? ?? ??????????
  ????? ?????????? ?? ?????????? ???????. ???????
  ?? ?????? ?????????? ??????? ??????????,
  ??????????? ? ??????? ?? ????? ????? ??????????.

37
?????????? ?? ??????????? ?? ??????????

• ?????? ?? ?????????, ??
• ????????????? ??????? ? ????????? ? ???????,
  ????????? ???????????? ?? GMP ? GLP
• ?????????????? ?? ?????????? ???????? ?? ?????
  ??????????

38
?????? ?? ?????????, ??

• ?????? ?? ?????? ????? ?? ??????????????,
  ?????????? ? ?????????? ?? ????? ?????????? ?
  ?????????? ?? ???????????? ? ????????? ???
  ????????????? ??????? ???????? ? ??????????
  ?????????

39
?????? ?? ?????????, ??

• ????????? ?? ?????? ????????? ?????????? ??
  ?????????? ????????, ???????? ??????? ? ????????
  ????????? ? ???????? ? ???????????? ? ???????????
  ????????? ? ????????????
• ????????????? ??????? ?? ?? ??????? ?????
  ??????????????? ???? ?? ? ????????????, ?? ?????
  ??????? ???????? ?? ???????????? ?? ???????? ?
  ???????????

40
?????? ?? ?????????, ??

• ?????????? ? ????????? ????????? ? ???????? ??
  ?????????? ?? ?????????????, ???? ?????
  ?????????? ?? ??????? ????????????? ?
  ????????????? ?? ????????? ?? ??????????? ??
  ??????????.

41
?????? ?? ?????????, ??

• ?????????? ???????? ? ??????? ??????????, ??
  ????????? ????????? ???????????? ?? ???????? ??
  ??????, ????? ? ????????? ????????? ?????????? ?
  ????????? ???????????? ????????, ?????????? ??
  ???????. ?????????????? ?????????? ????????????
  ?????? ?? ??????? ?????? ?????????? ?????.

42
?????? ?? ?????????, ??

• ??????? ? ????????? ?? ????????????
  ???????????? ?? ?????? ?? ???? ???? ?? ????????
  ??????????? ? ?? ???????????? ????????? ?
  ?????????? ?? ????????. ????????????? ?????? ??
  ???? ?????????, ?? ?? ???????? ? ??????????
  ?????????. ???????????? ???????? ?? ?????? ??
  ?????? ? ??????? ? ????????????? ????????.

43
?????? ?? ?????????, ??

• ??????????? ?? ?????????? ???????? ???????
  ?????? ?? ???? ????????? ? ????????? ?? ????????
  ?? ??????????? ???? ?????????? ?? ? ???????? ??
  ?????????????? ?? ??????????????. ?????? ??
  ??????????????? ??????????? ? ???????? ?
  ?????????? ?? ????????? ?? ????????, ?? ??
  ??????? ?????? ?? ?? ??????????? ????? ??
  ?????????? ? ?????????????? ?? ???????????? ?????
  ? ??????????? ?? ????????? ????, ?????????? ????,
  ???????, ??. ???????.

44
????????? ???????

• ???????????? ??????? ? ???? ???? ?? GMP, ????? ??
  ?????? ?? ?????????????? ? ???????????? ??
  ?????????, ?????????? ? ???????? ???????????
  ????????. ??? ????? ????????? ??? ?????????????,
  ?????????????? ? ??????????? ?? ???????????????
  ?? ????????????? ????????, ????? ?????? ??
  ?????????, ?? ?????? ?????????? ? ??????????
  ?????????? ?? ???????????? ????????? ?
  ???????????? ? ??????????? ????????????.

45
????????? ???????

• ???????? ???????, ???????? ??????? ?? ??????????
  ? ??????? ???????, ????????? ?? ????????????
  ????????

46
???????? ??????? (IN PROCESS CONTROL),

• ?? ????? ? ????????? ??????????????? ????????.
• ????? ?????????????, ???? ? ????????????????
  ???????? ?????? ?? ???? ?? ???????????? ????????
  ??????????

47
1.????????????

• 2. ??????? ?? ??????? ?? ?????
• 3. ?????????, ???????? ?
  ??????????? ? ???? ????????
• 4. ????????? ???????.

48
?????????? ?????????

• ?????? ?? ????? ??????? ? ????????, ????????
  ???????? ????? ????????? ?? ??????????,
  ?????????? ? ?????????, ????? ? ?????????.

49
???????? ?? ?????????

• ?????????????? ?????? ?? ??????? ?????????? ??
  ????? ????????, ????????? ? ???????????????? ????
  ??? ? ??????????? ??????????? ????? ? ??
  ?????????? ?????? ????????, ????? ???????? ????
  ????? ????????? ??? ???? ?? ?????? ??????? ?????
  ?????????? ?? ??????????.

50
??????????????? ????????

• ?????? ?? ?????? ??????? ???????? ?? ?????? ?
  ???????? ?? GMP. ?????????? ?? ???????? ?????? ??
  ????? ???????? ?? ???????????? ?? ?????
  ???????????? ? ?? ???????????? ?? ?????
  ????????? ???????.

51
?????????? ? ?????????? ?? ???????????

• ?????????? ?? ??????????? ??? ?????????? ???????
  ? ????? ??????? ?? ??????????? ?? ?????????? -
  ?? ???? ?????? ?? ?????????? ? ??????????????, ?
  ?? ????? ?????? ? ???????? ?? ???????? ??????.

52
????????????

• ??????? ???????????? ???????????? ????????? ????
  ?? ????????? ?? ??????????? ?? ??????????.

53
????????????

• ???????? ???????? ?? ????????????, ?? ?????
  ?????? ?? ????????? ?????????? ??? ???????????,
  ???????? ??? ?????????? ?? ??????? ??
  ??????????????

54
????????? ?? ????????????

• ???????? ????????? ? ????????? ????????,
  ???????????? ????????? ? ??????? ?????????? ?
  ????????. ??????? ???????? ???????? ??
  ???????????????? ???????, ??????????? ?
  ??????????? ????? ?? ????????????

55
???????? ???????????? (???????? ?????) -

• ?????? ?????????, ???????? ? ?????????????? ??
  ?????????, ????? ?????????? ?? ?? ???????
  ???????????? ?? ????????? ?? ?????????????? ??
  ????????? ?? ????????? ???????? ? ?????????????
  ????????? ?? ??????? ????????? ??????????.

56
????? ???????? ??

• ??????????????? ?????? ?????? ?? ?? ????????????
  ??????????, ????? ?? ?????????, ?? ?? ??
  ??????????, ?? ???????????? ? ????????? ????? ??
  ????? ? ?????????? ?? ?????????? ????????. ??
  ????? ?? ??????????????? ?????? ?????? ?? ??
  ???????????? ?????? ????????, ????? ?? ?????????.

57
???? ????????????? ??,

• ??????????? ?????? ?? ?? ???????? ?? ??????,
  ????????? ?? ???????????????? ????????.
• ?????????? ????? ???????? ??????-????????? ?
  ??????????????? ???????????? ?? ?????????? ?
  ???????? ????????, ????????? ? ?????????? ??
  ??????????????? ??????? ?? ???????????? ???????.

58
????? ??????????? ???????? (GLP)

• ??????? ?? ???????, ????????? ????????? ??
  ?????????, ????????? ?? ????????????, ??????????,
  ???????????? ? ????????????? ?? ?????????????
  ??????????

59
??????????? ?? ?????????

• ???? ?? ??????????? (TEST FACILITY) ???????
  ?????????, ???????????, ???????????? ?
  ???????????, ?????????? ?? ?????????? ??
  ???????????.

60
??????????? ?? ?????????

• ??????????? ?? ??????????? (?????? ????????????)
  (STUDY DIRECTOR) ????, ????? ????????
  ?????????? ?????????? ?? ??????????? ?
  ???????????? ? ????????? ????.

61
??????????? ?? ?????????

• ?????????? ?? ??????????? ??????, ????? ???
  ???????????, ?? ????? ? ????????? ???????????? ??
  ???????????.

62
??????????? ?? ?????????

• ???????? ?? ??????????? ?? ?????????? (QUALITY
  ASSURANCE PROGRAMM) ??????? ?? ????????
  ???????, ??????????? ?????????? ?? ??????????? ?
  ???????????? ? ??? ???? ????????? ?? ???????????
  ?/??? ???????? ?? ????????????.

63
??????????? ?? ?????????

• ??????????????? ?????????? ?? ?????? (STANDARD
  OPERATING PROCEDURES) ??????? ??????????,
  ?????????????? ?????? ?? ?????????? ?? ???????
  ??????????? ????????, ????? ?? ?? ????????
  ??????? ? ????????? ??? ? ????????????? ??
  ?????????.

64
??????????? ?? ?????????

• ?????????? (SPONSOR) ????????? ??? ??????????
  ????, ????? ??????? ???????????? ?? ??????????? ?
  ?? ?????????.

65
??????????? ?? ?????????

• ????????? (STUDY) ??????????? ??? ???????? ??
  ????????????, ??? ????? ??????????? ???????? ??
  ??????? ?? ?????? ? ??? ?????????? ?? ????? ??
  ???????? ???????? ?/??? ??????????? ?? ?????????
  ?????? ? ???????? ?????.

66
??????????? ?? ?????????

• ???? ?? ??????????? (STUDY PLAN) ????????,
  ????? ???????? ??????? ?? ???????????.
• ???????? ?? ????????? (STUDY PROGRAMME)
  ????????, ????????? ??????? ?? ????? ??
  ?????????? ? ???????? ??????? ????? ?? ?????????.

67
??????????? ?? ?????????

• ???? ??????? (TEST SYSTEM) ????? ??????????,
  ??????????, ??????????? ??? ????? ????????,
  ???????????, ??????? ??? ??????? ??????? ???
  ?????????? ?? ???, ????? ????? ?? ????????
  ???????????, ? ????? ????????? ????? ??
  ???????????.

68
??????????? ?? ?????????

• ???????? ????? (RAW DATA) ?????? ????????
  ??????????? ?????? ? ?????????, ??? ?????
  ????????? ????? ?? ??????????? ?? ???????
  ?????????? ? ???????? ?? ????? ?? ???????????. ?
  ???? ????????? ?? ???????? ? ???????, ????????
  ??????? ? ???????? ??????????? ????????? ??
  ??????.

69
??????????? ?? ?????????

• ????? (SPECIMEN) ????????, ??????? ?? ????
  ??????? ?? ?????????? ?/??? ??????????.
• ????????? ???????? (TEST SUBSTANCE) ???????? ??
  ?????????? ?/??? ???????? ???????? (?/??? ????),
  ????? ??????? ?? ??????????.

70
??????????? ?? ?????????

• ?????????? ???????? (REFERENCE SUBSTANCE)
  ?????????? ??????? ?????????? (??? ????),
  ????????? ? ??????????? ????????, ?????????? ??
  ????????? ??? ??????????????.
• ??????? (VEHICLE) ?????, ????? ????? ??
  ????????, ???????????? ?/??? ?????????? ??
  ??????????? ??? ???????????? ????????.

71
????????????? ?? ?????? ?? ???????????

• ?? ????????? ?? ???????-?????? ??? ????????
  ?????????? ?? GLP ? ???????? ?? ?????????
  ??????????, ??????????, ???????????? ????????,
  ??????????????? ?????????? ?? ??????, ???????? ??
  ??????????? ?? ??????????, ??????? ??
  ????????????, ??????????? ?? ????????.

72
????????????? ?? ???????????

• ? ?????? ????????? ?? ???????????? ?? ? ?
  ?????????? ?? ????????? ????? ?? ???????????, ??
  ????????? ?????????? ?? ???????????, ?? ??????? ?
  ?????????? ?????????, ????? ??????????? ??
  ??????????? ?? ???????, ???????? ????????????
  ?????? ?? ???????????.

73
??????????, ????????? ???????????

• ?????? ?? ?????? ????????? ?? ???????????, ????
  ??????????? ?? ?????????? ?? ??????????? ???????.

74
?????????? ?? ??????????? ?? ??????????

• ????????? ?????????? ?? ???????????? ?
  ???????????? ? GLP, ????????? ?? ?? ????,
  ???????? ?? ???????????? ? ? ????????? ???? ????,
  ??????? ????????????????? ?????????? ?
  ??????????? ?? ?????????? ??.

75
???????????? ????

• ?????? ?? ???? ?????????? ? ???????????? ??
  ??????????? ? ?? ????????? ?????????? ??????????
  ?? ????? ??????? ?????????. ?????????? ??
  ????????? ??????? ?? ???????????????, ????????? ?
  ??????? ?? ?????????? ???????????? ???????????.
  ?????????? ? ??????????? ?? ????????? ????? ??
  ?????????? ?? ??????????? ? ????????????
  ????????, ????? ? ?? ?????????? ?? ????????.

76
???????????? ???? ??????? ? ?????? ???????

• ?????? ?? ?? ???????? ?? ????????? ?????? ??
  ????? ?? ?????????????? ??? ????????? ?
  ?????????? ?? ??????????? ??. ?????? ??
  ?????????? ?????????? ??????? ????? ???
  ???????????? ? ??????????? ??????? ?? ?????.

77
2

• ??????? ?? ???????? ??????? ? ???????? ???
  ??????????. ????????????????? ? ?????????? ??
  ????? ?????????? ????? ??? ?? ????? ??
  ??????????? ?????? ?? ???? ?????????????.

78
??????????? ? ?????????? ????????

• ?? ???????? ? ??????? ??? ???????????
  ??????????????, ??????????, ???? ?? ?????????? ?
  ??. ?????????? ?? ????? ??????? ?????????????,
  ???? ?? ???????, ?????????? ?? ??????????,
  ??????????????, ??????????.

79
????????????????? ?????????? ?? ??????

• ?????????? ?????????? ? ????????? ?? ???????,
  ???????? ? ???? ?? ??????????? ? ?????? ?????
  ???????????, ? ????? ?? ????????? ????????????.
  ???????? ?? ? ??????????? ? ?????????? ????????,
  ? ?????????????? ?????????, ? ???? ?????????, ?
  ????????? ?? ??????????? ?? ??????????.

80
????????? ? ?????????? ?? ???????????

• ???????? ?? ? ?????? ??? ??? ????????????? ??
  ????????????, ???? ?????? ???????? ????? ??
  ???????????, ????? ? ???????? ? ?????????? ??
  ???????????? ?? ? ?? ????????? ? ????????? ?????.

81
2

• ???????????? ?? ??????????? ? ? ???????????? ?
  ?????????? ????, ???? ?? ?????????????, ??????
  ????? ?? ???????? ? ??????????? ?? ????????? ??
  ????????????, ???????? ???? ?????? ??? ??????????
  ?????????????? ??????? ?? ????? ??????? SI.

82
?????????? ?? ?????????? ?????????

• ??? ?? ?? ??????, ?? ???????????? ??????????
  ???????? ?? ????????? ?? ???????????????? ??.

83
????????, ????????? ?? ??????????

• ?????????? ?? ???????, ?? ????? ?? ??????? ?? ??
  ? ????????? ?? ?????????? ?????? ??????? ??
  ?????????
• ?????????? ?? ???????, ????? ?????????? ??
  ???????? ????????????
• ?????????? ?? ???????????
• ???????????? ???????????.
• ????????? ?? ????????? ??????????? ??
  ????????????? ???????? ????? ???? ???????.

84
?????????? ?????????

• ?????????? ??????? ?? ???????????? ?????
  ?????????? ? ?????????????? ????????. ???????? ??
  ???? ?? ?????? ???????? ?? ?????????? ???
  ??????????? ?????.

85
?????????? ?????????

• ?????????? ??????? ?? ???????????? ??
  ??????????? ?? ????????? ??????????.
• ???????????? ???????????? ??? ??????? ?????????
  ?? ???????
• ???????? ?????????? ???????????? ? ??????
  ??????????? ? ???????? ???????, ?????? ??
  ???????? ???????????
• ???????????????? ???????????? ?? ????????
  ???????????

86
(No Transcript)
87
?????????? ?????????

• ???????????? ???????? ?????????? ?????????
  ????? ????????? ?? ?????????? ??????? ??
  ???????????? ?? ??????????? ?? ?????????
  ??????????.

88
??????????? ??????????

• ??????? ?? ???????????? - ???-???????
  ??????????? ????????????
• ??????? ?? ???????????? ?????????? ???-???????
  ??????????, ????? ???? ?? ???? ?????????? ?
  ????????? ?????????? ? ????????????????

89
2

• ????????? ?????????? ????? ??????? ?
  ???????????? ?? ???????
• ?????? ?????????? ????? ??????????? ?
  ?????????? ????????????, ?? ????? ? ????????, ??
  ???????????? ???????? ????????? ??????????,
  ???????????????? ? ?????????.

90
??????????? ?? ?????????? ?? ????????????
?????????

• ???????????? ????????????????? ?????? ?????
  ?????????????? ?????? ?? ?? ???? ?? ????? ??
  ???????????? ?? ????????? ?? ???????????,
  ?????????? ?? ?????????????? ? ??????? ??
  ????????? ?? ????? ?? ????????.

91
2

• ???????????? ????????? ??????? ?? ??????. ??
  ?????? ???? ?? ?? ??????, ?? ???? ??????????
  ????? ? ?????????? ?? ???? ??????? ?????? ? ??
  ?????????? ?????????? ?? ??? ??? ?????? ??????,
  ?? ?? ?? ???????? ???????????? ???? ??
  ?????????????.

92
(No Transcript)
93
?????????

• ??? ???????????? ?? ?????????, ??????????? ??????
  ?? ?? ???????? ? ???????? ????????????? ?????,
  ???????? ???? ??????????? ?? ????????????? ?????
  ? ??????? ?? ?????? ?? ???-??????? ????????.
  ???????? ?? ????????? ?????????? ??? ??????? 5
  ???????? ????????????.

94
??????

• ????????? ?? ????????????? ?? ????????? ? ??????
  ?? ???????? ?????????? ?? ????? ?????.
  ??????????? ????, ?? ???????????? ?????????
  ????????? ????????????? ?????? ?? ?????????,
  ?????????? ? ??????????.

95
???????

• ???????? ?? ?? ??????? 9 ?????????? (3 ??????????
  ??? 3 ???????? ????????????). ?????? ?? ??
  ???????? ???? ???????? ?????????????? ????
  ????????? ?? ???????? ?????????? ?? ?????????????
  ???????? ? ??????? ??? ???? ??????? ?????
  ???????? ? ???????? ???????? ???????? ?????? ?
  ????????????? ?????????.

96
??????????

• ?????????????? ?? ???????????? ? ???? ??????? 9
  ???????????, ?????????? ??????????? ?????? ??
  ??????????? (3 ?????????? ??? 3 ????????
  ????????????) ??? ???? ??????? 6 ??????????? ???
  100 ?? ????????? ????????????

97
2

• ?????????????? ?? ???????????????? ?? ???????
  ???? ???????????????? ???????????? ? ?? ??????? ?
  ?????? ?? ??????????????? ?? ??????????
  ?????????.

98
?????????????? ?? ??????

• ???????? ?? ?? ??????? ??????
• ???? ???????? ??????
• ????????? ????? ??????? ?? ????? ? ????????
  ???????????? ?? ????????????? ???????? ? ????
  ???????????? ?? ??????????? ????, ??? ?????
  ?????????? ???? ?? ???? ??????????

99
2

• ???? ????? ?? ???????? ?? ?????????? ?? ????????
  ? ??????? ?? ???????.
• ???? ?????, ??????? ?? ???????????? ?????????? ??
  ?????-???????
• ???? ?????, ??????? ?? ????????????? ?????.

100
???????????? ???????

• ???????? ?? ??? ?????? ??
• ???????? ??????
• ??????????? ??????-???
• ????? ?? ???????? ?? ???????????? ?????????? ??
  ???????? ? ??????? ?? ???????

101
???????? ?? ??????????? ?????

• ??????????? ?? ?????????? ?? ?????? ?? ????????
  ?? ????, ?? ????? ?? ????????? ????????? ??
  ??????????, ?? ?? ???????? ??????????? ??
  ???????????? ?????????.

102
?????????? ?? ?????????

• ????????? ?? ???????? ?? ?????????? ?? GLP ??
  ????????? ?? ????????? ???????? ????? ???
  ???????, ???????, ??????????????, ??????????????,
  ???-?????????????? ? ?????????? ?????????.
  ?????????? ? ???????? ????????? ?? ??????????,
  ?????????? ?????????? ? ????????? ??
  ????????????? ?? ?????? ?? ???????????.

103
????????????

• ???? ?????? ?? ??????????? ?????????? ? ?????????
  ???????? ? ???????????? ??????????, ?? ????
  ?????????? ? ???????? ???? ?? ????????????
  ????????.

104
????? ?? ???????????

• ????????????? ????
• ?????????? ? ?????????? ????? ?? ???????????
  (??????????, ?????????, ?????? ? ?.?.), ????? ?
  ??? ?? ????????????.

105
2

• ???????????? ? ?????????? ?? ?? ?????????
  ????????????? ? ??????, ????? ?? ??????? ?
  ?????????????? ?????????? ???????? ??????? ??
  ???????? ?????????, ????????????? ??????????????
  ? ??.

106
3

• ????????????? ?????? ?? ????? ??????????? ??
  ??????, ????, ????? ? ?????????? ???????????????
  ?? ??????????? ?? ????????????.

107
????????? ?????

• ????????????? ? ????????? ?? ?????? ?? ?????????
  ?? ????????? ?? ??????????? ??? ?????????? ??
  ??????????? ?????????. ???????? ?? ????? ?
  ??????? ?? ???????????, ??????????????,
  ??????????? ??????????, ??????????? ?? ??????,
  ????? ?? ????? ????????? ?? ???????????.

108
?????????? ?? ???????????

• ??????????? ? ???????? ?? ??????, ?????? ??
  ???????? ??????????? ?? ????????? ??
  ???????????? ????????, ????? ???????,
  ?????????????? ?????????, ???????? ?? ???????? ?
  ?????? ????? ???????? ?? ?????????.

109
???????????? ????????

• ??????? ?? ?????? ? ?????????, ????? ??
  ?????????? ? ?????? ??????????? ?? ??????,
  ????????????? ?????????-?????, ?????? ?? ?????? ?
  ????????? ??????????, ???????? ?? ?????????
  ?????????? ? ???????? ?? ?????????, ???????
  ??????????????? ?????????? ? ??.

110
???????? ?? ??????????? ?? ??????????

• ???????? ????????? ?? ?? ??????????? ?
  ??????????? ?????????? ?? ?????????? ?? GLP.

111
2

• ?????????? ?? ????????? ? ???????? ??
  ???????????? ? ???????, ???????????? ??
  ?????????????? ? ????? ????????, ??????????????
  ?? ??????? ?? ?? ?? ?????????, ??????? ?
  ????????????, ?????????, ???????? ?
  ??????????????? ?? ???????? ????? ??????????,
  ??????????, ?????????? ?? ??????? ?? ?? ???
  ???????? ??????????, ????????? ?? ??????? ?? ?? ?
  ????????, ???????????? ? ???????????? ??
  ??????????????????? ?????????? ?? ??????.

112
?????????? ????

• ?? ?? ???????? ???? ?????? ???????? ??
  ???????????? ?? ???????????? ??????????,
  ??????????? ? ???????? ?? ? ??????? ?? ????????
  ?????, ????????? ?? ?????? ? ??????????.
• ?? ?? ???????? ???? ?????? ?? ??????????? ???
  ????????? ???????, ?????????, ???????? ? ???????
  ? ?????????, ?????????? ?? ???????????? ?? GLP.

113
2

• ?????????? ?? ???????????? ???? ??????? ??
  ????????? ??????? ? ??????? ????????, ??????????,
  ????????? ?? ? ????????? ????????? ??
  ????????????, ?????????? ????? ???? ? ????
  ??????, ?????????? ?? ?? ??????? ?? ??????????.

114
?????????? ?? ??????????? ?? ???????????

• ???????????? ? ???????? ?????? ???????? ???????
  ??????? ? ?????????????????? ?? ?????????? ??
  ???????????? ? ?????????? ?? GLP.

115
??????

• ???? ?????????? ??????? ?????? ?? ???????????,
  ???? ?? ??????????? ?????????, ????????-????
  ?????????? ?? ?????????? ?? GLP.

116
?????????

• ??????? ?????????? ??????? ????????????? ??????
  ?? ?????????, ????? ?? ???????????? ?? ??????,
  ????? ?? ???????????? ?? ???????????,
  ????????????? ?? ?????????????, ? ????? ?
  ???????????? ?? ????? ?? ??????????, ??? ??
  ???????????, ??????????, ??????? ?????? ?????????.

117
?????????

• ??????? ????? ??? ???????? ???????? ??
  ???????????? ? ??????????? ?? ????? ??
  ??????????.

118
2

• ???????????? ??????? ????? ??????? ??????????????
  ????????? ? ?????, ???????? ?? ??????????? ??
  ??????????, ?????????? ????, ???? ???????,
  ?????????? ? ?????????? ????????,
  ????????????????? ?????????? ?? ??????,
  ?????????? ?? ???????????, ???????? ??
  ??????????? ?? ???????????, ??????????? ?
  ????????? ?? ???????, ?????????????? ??????????
  ?? ?????????? ?? GLP ???????? ??????? ?
  ????????.

119
???????? ?? ?????????????? ?????????

• ?? ?????????????? ????????? ?????????? ?? ????
  ?????? ????????????, ?? ????? -????????????? ??
  ?????? ?? ??????????? ? ?? ??????????
  ???????????? ?? GLP. ? ??????? ?? ????????
  ??????????? ??????????-?? ?????????. ????????? ??
  ?????? ?? ????????????.

120
??????????

• ????????? ?? ???????? ?? ??????????, ???????
  ???????? ?? ???????????? ? ?????????? ?? GLP.

121
??????????

• ???????? ????? ?? ????????? ? ??????? ?????????.

122
?????????

• ???????? ?????? ?? ???? ???????? ? ??????? ??
  ??????? ?????????, ????? ? ?? ????? ??????????,
  ????????? ? ?????????? ? ???????????? ? ???????
  ????????????.