Demystifying GMP

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De-mystifying GMP ??GMP Dr Bob Pietrowski Bob
Pietrowski ?? David Begg Associates
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De-mystifying GMP??GMP

• Introduction ??
• Quality Assurance, GMP and Quality Control
• ????,GMP?????
• What is GMP ? ???GMP ?
• Legal Status of GMP GMP?????
• GMP The Industry and the Regulators
• GMP????????
• Essential Elements of GMP GMP?????
• Summary ??
• Essential Messages ????

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MORAL and LEGAL Obligations of Manufacturers?????
??????

• To organize their activities so that
• ??????????
• Products are FIT FOR INTENDED USE
• ?????????
• Comply with REGULATORY COMMITMENTS
• ????????
• Patients not at risk because of inadequate
• ?????????,????????
• SAFETY??
• QUALITY??
• EFFICACY??

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EU Guide to GMP ...????GMP???

• ATTAINMENT of QUALITY OBJECTIVE
• ??????
• Is responsibility of SENIOR MANAGEMENT
• ?????????
• Requires PARTICIPATION and COMMITMENT by
• ??????????????
• Staff in many Departments and at all
  levels?????????????
• The Companys Suppliers??????
• The Companys Distributors??????

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To Achieve the Quality RELIABLY there must be a
...????????,???...

• COMPREHENSIVELY DESIGNED and CORRECTLY
  IMPLEMENTED system of QUALITY MANAGEMENT
  incorporating ...
• ?????????????????, ????
• ? QUALITY ASSURANCE ????
• GOOD MANUFACTURING PRACTICE??????(??????????)
• QUALITY CONTROL????

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Quality Assurance ...????...

• The CREATION and OPERATION of
• ?????
• STANDARDS ??
• PROCEDURES ??
• MANAGEMENT SYSTEMS????
• To GUARANTEE the QUALITY of a PRODUCT throughout
  its LIFE CYCLE
• ?????????? ???

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• ALL FACTORS... inside and outside the factory
• ??????????????...
• BEFORE, DURING AND AFTER MANUFACTURE
• ?????,?????????

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Good Manufacturing Practice ??????

• Part of Quality Assurance aimedat ensuring that
  products are
• CONSISTENTLY MANUFACTURED
• to the REQUIRED QUALITY
• within the FACTORY
• ??????????????????????????????????

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Quality Control... Part of GMP????...GMP????
Tests, inspections and measurements carried out
on SAMPLES taken before, during and after
MANUFACTURING and PACKAGING to provide evidence
that a starting material or a finished product
will or will not meet its WRITTEN
SPECIFICATION ????????,??????????????????,????????
????????????????????
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Quality Control is Concerned With ??????

• Sampling programmes ????
• Specifications ??
• Testing ??
• PHYSICAL CHEMICAL BIOLOGICAL
• ???????????????
• Documentation ??
• Standards ??
• Release procedures ????
• and GOOD CONTROL LABORATORY PRACTICE
• ???????????

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What is GMP ? GMP ????
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GMP stems from recognition that QUALITY can be of
TWO types ...GMP????????????????...

• INTRINSIC ???
• inherent suitability of active in a particular
  formulation
• ????????????????
• safety and efficacy of the formulated product
  when made correctly and used as indicated
• ???????????????????????
• EXTRINSIC ???
• suitability of any batch of a manufactured
  product
• ????????????
• quality determined by the manufacturing
  practices
• ??????????

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Extrinsic Quality depends on ???????

• Quality of starting materials
• ??????
• Quality of Premises and Plant
• ???????????
• Suitability of the Process
• ??????
• Absence of Processing Problems
• ????????
• Quality of In-Process Controls
• ???????
• Training and Attitude of People
• ????????
• ... in short GMP GMP????

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GMP is concerned with ...GMP??...

• All activities ...?????
• Delivery of materials a Release of products
• ?????a ?????
• All processes ...?????
• Logistics a Manufacturing Packaging
• ??a ????
• Quality Control ...????
• Materials a In-process a Finished Products
• ??a??a??
• Good Management ...?????
• People a Data a Communications
• ??a ??a ??

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Principles of GMP ...GMP ???...

• People??
• Premises??
• Products??
• Processes??
• Procedures??

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The Legal Status of GMP GMP?????
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Legal Status of GMP in USA ...GMP????????
GMP has been LAW since 1962 ?1962???,GMP????
Current Good Manufacturing PracticeRegulations
(cGMPs) detailed inCODE of FEDERAL
REGULATIONS (Title 21 - Food and Drugs - Parts
210 and 211) ???????????????cGMPs????????? (??21-?
????-210?211??)

• Legally binding regulations in USA
• ???,?????????
• Updated annually - hence current
• ???? - ???????

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GMP -Good Manufacturing PracticeGMP- ??????
GMPs mean the requirements found in the
respective legislations, regulations, and
administrative provisions for methods to be used
in, and the facilities or controls to be used
for, the manufacturing, processing, packing,
and/or holding of a drug to assure that such drug
meets the requirements as to safety, and has the
identity and strength, and meets the quality and
purity characteristics that it purports or is
represented to possess GMPs???????????????????????
?/????????????????????????????,?????????,?????????
?,????????????????? ?
21 CFR 210.1(a) 21-????- 210.1(a)
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Legal Status of GMP in USA ...GMP????????...

• Regulations cover ... ????...
• ORGANISATION and PERSONNEL?????
• BUILDINGS and FACILITIES????????
• EQUIPMENT??
• CONTROL of Components, Drug Product Containers
  and Closures
• ??,????????????
• PRODUCTION and PROCESS CONTROLS????????
• PACKAGING and LABELLING CONTROLS????????
• HOLDING and DISTRIBUTION?????
• LABORATORY CONTROLS?????
• RECORDS and REPORTS?????
• RETURNED and SALVAGED DRUG PRODUCTS???????

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Legal Status of GMP in EU...GMP????????

• 1970s European Countries publish GMP guides
• 20??70?? ???????GMP??
• First EC Guide to GMP
• 1989 ??????GMP??
• Compliance with GMP made compulsory in all member
  states
• 1992 ????????GMP??????
• Compliance with GMP extended to cover IMPs
• 2004 GMP?????IMP(??????)?

Directives ... THE LAWGMP Guidelines ...
INTERPRETATION ?? ... GMP????? ...??
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GMP ... Good Manufacturing PracticeGMP ...??????
That part of QUALITY ASSURANCE which ensures that
products are consistently produced and controlled
to the quality standards appropriate to their
INTENDED USE ?????????,???????????????????????????
??? EU Volume IV of the RulesGood Manufacturing
Practice for Medicinal Products ?????IV? ????????

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Legal Status of GMP in EU...GMP????????

• GMP Guidelines ... interpretation of GMP
  directives
• GMP????...GMP?????
• QUALITY MANAGEMENT????
• PERSONNEL??
• PREMISES and EQUIPMENT?????
• DOCUMENTATION??
• PRODUCTION??
• QUALITY CONTROL????
• WORK CONTRACTED OUT?????
• COMPLAINTS and PRODUCT RECALL???????
• SELF-INSPECTION??
• Annexes on specialised topics
• ?????

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EU and US GMP Requirements??????GMP????

• Underlying PRINCIPLES and PHILOSOPHY of GMP are
  similar ... and especially concerned with
• GMP??????????????...?????
• PEOPLE??
• PREMISES??
• PROCESSES??
• PRODUCTS??
• PROCEDURES??

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GMP ... Industry and Regulators GMP ... ????????
GMP ... the way in which appropriate product
quality is reliably achieved ! GMP
...??????????? THERE is NOTHING MYSTERIOUSabout
GMP ! ??GMP,?????????! Nor is it simply the
figment of the imagination of the REGULATORY
AUTHORITIES ??????????????????
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GMP ... Industry and Regulators GMP ... ????????
It is a DISTILLATION of ACCEPTED GOOD
PRACTICES agreed between Industry and
Regulators ????????????????????????
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Perusal of GMP Guidelines ...GMP?????...
PICS ????????
etc
WHO ??????
EU ??
FDA ???????

• Nothing which responsible manufacturers do not
• ?????????
• agree with???
• strive to comply with - in practice?????????????
• Why should GMP INSPECTION sometimes turn into a
  PAINFUL and CATACLYSMIC event ?
• ???GMP????????????????????

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Reason ????

• No difference in philosophy and principles of GMP
  ...
• GMP?????????????...
• ... BUT
• ...??
• Difference in INTERPRETATION of HOW to achieve
  these principles in practice ... and the WAY in
  which manufacturers RESPOND
• ???????????????... ?????????????

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The Secret of Success ????? Getting the Basics
Right ???????
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Essential Elements of GMPGMP?????
Basic requirements ????

• All manufacturing processes are
• ???????
• Clearly defined ?????
• Systematically reviewed in the light of
  experience
• ????,????????
• Shown to be capable of consistently manufacturing
  medicinal products of the required quality and
  complying with their specifications
• ?????????????????????????
• Critical steps of manufacturing processesand
  significant changes to the process are validated
• ?????????????????????

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Essential Elements of GMP GMP?????
Basic requirements????

• All necessary facilities for GMP are provided,
  including
• ????GMP???????,??
• ? Appropriately qualified and
  trained personnel
• ????????????
• Adequate premises and space ????????
• Suitable equipment and services ????????
• Correct materials, containers and labels
  ?????,?????
• Approved procedures and instructions ????????
• Suitable storage and transport ????????
• Instructions and procedures are written in an
  instructional form in clear and unambiguous
  language, specifically applicable to the
  facilities provided
• ????????????????????????,??????????????

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Essential Elements of GMP GMP?????
Basic requirements????

• Operators are trained to carry out procedures
  correctly ???????,??????????????
• Records are made, manually and/or by recording
  instruments, during manufacture which demonstrate
  that ??????,???????????????,?????
• All the steps required by the defined procedures
  and instructions were in fact taken
• ??????????????????
• The quantity and quality of the product was as
  expected
• ?????????????
• Any significant deviations are fully recorded and
  investigated
• ???????,????????????

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Essential Elements of GMP GMP?????
Basic requirements????

• Records of manufacture and distribution, which
  enable the complete history of a batch to be
  traced, are retained in a comprehensible and
  accessible form
• ???????,??????????,??????????????
• The distribution of products minimises any risk
  to their quality
• ????????????????????
• A system is available to recall any batch of
  product from sale or supply
• ???????????????????
• Complaints about marketed products are examined,
  the causes of quality defects investigated and
  appropriate measures taken in respect of the
  defective products and to prevent reoccurrence.
• ?????????,?????????,????????????????????

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Specific Requirements for Quality
Control?????????

• Samples are taken by methods and by personnel
  approved by QC
• ?????????????????????
• Test methods are validated
• ?????????
• Product assessment shall be performed, including
  a review and evaluation of relevant production
  documentation and an assessment of deviations
  from specified procedures
• ???????,???????????????,?????????????

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Specific Requirements for Quality
Control?????????

• No material shall be released for manufacture, or
  product released for supply, if it fails to meet
  its approved quality specification
• ??????????????,?????????,??????
• Sufficient reference samples of
• Starting materials
• Products
• shall be retained to permit future examination
  if necessary
• ??????
• ??? ???
• ????????,???????????

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Additionally ??

• Regular or rolling quality review of all products
  shall be conducted
• ????????????????????
• To verify ???
• The consistency of the existing process????????
• The appropriateness of current specifications
• ??????????
• To highlight any trends ????????
• To identify the need for improvements to
• Products
• Processes
• ???? ??? ???????

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And Finally ??

• There shall be a procedure for Self- Inspection
  and/or Quality Audit to appraise the
• effectiveness
• relevance
• of the Quality Assurance System
• ?????????????????????????/?????????

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SUMMARY ??
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Summary ...??...
GMP is a natural consequence of the central role
that PEOPLE and the PROCESS play in the
achievementof QUALITY GMP???????????????????? It
is GUIDELINES and GOOD PRACTICES developed via
CONSULTATION and CONSENSUS between MANUFACTURERS
and REGULATORS GMP????????????????????????????????
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Summary ...??...

• GMP seeks to minimise the VARIABLES which affect
  quality such as
• GMP?????????????,?
• Materials??
• Processes/methods of manufacture?????????
• Equipment??
• Environment/Premises??/??
• People??

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Summary ...??...

• These VARIABLES may be controlled by
• ????????????????
• Testing, inspecting, measuring??,?????
• Documenting ??
• Validating ??
• Calibrating ??
• Monitoring ??
• Maintaining (eg Planned Preventative Maintenance)
  
• ?? (??????????)
• Self-Inspection and Auditing ?????
• Housekeeping ????
• Training ??

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Essential Message ...????...

• GMP is about GMP ???
• People ??
• Premises ??
• Processes ??
• Products ??
• Procedures ??

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Essential Message ...????...
Assurance of the required quality cannot be
achieved by testing alone ??????????????
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Essential Message ...????...
GMP is only one important element that determines
the total quality of a product GMP????????????????
???
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Essential Message ...????...
Achievement of quality assurance doesnt happen
by accident?????????????? - it is the result of
careful planning and installation of a QUALITY
SYSTEM,????????????????? but a system is like a
chain - only as strong as its weakest link
! ????????????-???????????????
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Essential Message ...????...

• Quality Assurance is ?????
• an attitude of mind ! ??????
• a team job ! ???????
• the responsibility of everyone in the company !
  ???????????

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STAND E1C13
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