Six System Inspection Model

1. UNIT 3
Six system inspection model
Dr. Vichare V S
PES Modern College of Pharmacy (for ladies), Moshi, Pune

2. QUALITY MANAGEMENT SYSTEM
• A QMS is a collection of business processes focused on
consistently meeting customer requirements and
enhancing their satisfaction.
• It is expressed as organizational goals and aspirations,
policies, processes, documented information and
resources needed to implement and maintain it.
• Early QMS emphasized
predictable outcomes of an
industrial product production
line, using simple statistics
and random sampling.
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3. SIX SYSTEM INSPECTION MODEL
• A model that can help pharmaceutical manufacturers
comply with cGMP regulation. The six systems referred
to in this inspection model are:
1. Quality System
2. Production System
3. Facilities and
equipment system
4. Laboratory control
system
5. Material system
6. Packaging and
labeling system
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4. INTRODUCTION
• The FDA's Drug Manufacturing Inspection Compliance
Program, which contains instructions to FDA personnel
for conducting inspections, is a systems-based approach
to inspection and is very consistent with the robust
quality system model presented in this guidance.
• The quality system provides the foundation for the
manufacturing systems that are linked and function
within it.
• The quality system model described in this guidance
does not consider the five manufacturing systems as
discrete entities, but instead integrates them into
appropriate sections of the model.
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5. • Those familiar with the six-system inspection
approach will see organizational differences in this
guidance; however, the inter-relationship should be
readily apparent.
• One of the important themes of the systems based
inspection compliance program is that you have the
ability to assess whether each of the systems is in a
state of control.
• The quality system model presented in this
guidance will also serve to help firms achieve this
state of control.
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6. • Pharmaceutical manufacturers should implement
modern quality systems with risk management
approaches to meet the requirements of the
Agency's current good manufacturing practice
(cGMP) as per regulations 21 Code of Federal
Regulations (CFR) parts 210 and 211.
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7. 1. Quality System
• This system assures overall compliance with cGMP
and internal procedures and specifications.
• The system includes the quality control unit and all
of its review and approval duties (e.g., change
control, reprocessing, batch release, annual record
review, validation protocols, and reports, etc.).
• It includes all product defect evaluations and
evaluation of returned and salvaged drug products.
• Inspection is carry out according to cGMP
regulation, 21 CFR 211 Subparts B, E, F, G, I, J, and K.
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8. • Subpart B - Organization and Personnel
1. Responsibilities of quality control unit.
2. Personnel qualifications.
3. Personnel responsibilities.
4. Consultants.
• Subpart E - Control of Components and Drug Product Containers and
Closures
1. General requirements.
2. Receipt and storage of untested components, drug product
containers, and closures.
3. Testing and approval or rejection of components, drug product
containers, and closures.
4. Use of approved components, drug product containers, and closures.
5. Retesting of approved components, drug product containers, and
closures.
6. Rejected components, drug product containers, and closures.
7. Drug product containers and closures.
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9. • Subpart F - Production and Process Controls
• Written procedures; deviations.
• Charge-in of components.
• Calculation of yield.
• Equipment identification.
• Sampling and testing of in-process materials and drug products.
• Time limitations on production.
• Control of microbiological contamination.
• Reprocessing.
• Subpart G - Packaging and Labeling Control
• Materials examination and usage criteria.
• Labeling issuance.
• Packaging and labeling operations.
• Tamper-evident packaging requirements for over-the-counter (OTC)
human drug products.
• Drug product inspection.
• Expiration dating.
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10. • Subpart I - Laboratory Controls
• General requirement.
• Testing and release for distribution.
• Stability testing.
• Special testing requirements.
• Reserve samples.
• Laboratory animals.
• Penicillin contamination.
• Subpart J - Records and Reports
• General requirements.
• Equipment cleaning and use log.
• Component, drug product container, closure, and labeling records.
• Master production and control records.
• Batch production and control records.
• Production record review.
• Laboratory records.
• Distribution records.
• Complaint files.
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11. • Subpart K - Returned and Salvaged Drug
Products
• Returned drug products.
• Drug product salvaging.
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12. 2. Production System
• This system includes measures and activities to
control the manufacture of drugs and drug products
including
• batch compounding
• dosage form production
• in-process sampling and testing
• process validation
• It also includes establishing, following, and
documenting performance of approved
manufacturing procedures.
• Inspection is carry out according to the cGMP
regulation, 21 CFR 211 Subparts B, F, and J.
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13. • According to the cGMP :
• Quality and manufacturing process and procedures
(and changes to them) must be defined, approved
and controlled.
• Batch numbering and maintaining proper
traceability is required/process validation is
required. – Track batch, equipment use records and
labeling used, personnel, raw material controls are
traceable.
• Verification of all steps including sign-off are
required for critical process steps.
• Verification/ validation of computerized processes.
• All batch records must be reviewed and have QA
approval before the product is released.
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14. 3. FACILITIES AND EQUIPMENT SYSTEM
• This system includes the measures and activities which provide an
appropriate physical environment and resources used in the
production of the drugs or drug products.
• It includes:
• a) Buildings and facilities along with maintenance;
• b) Equipment qualifications (installation and operation);
equipment calibration and preventative maintenance; and
cleaning and validation of cleaning processes as appropriate.
Process performance qualification will be evaluated as part of the
inspection of the overall process validation which is done within
the system where the process is employed;
• c) Utilities that are not intended to be incorporated into the
product such as HVAC, compressed gases, steam and water
systems.
• Inspection is carry out according to the cGMP regulation, 21 CFR
211 Subparts B, C, D, and J. 14

15. • 21 CFR 211 Subparts B, C, D, and J:
• Subpart C - Buildings and Facilities
• Design and construction features.
• Lighting.
• Ventilation, air filtration, air heating and cooling.
• Plumbing.
• Sewage and refuse.
• Washing and toilet facilities.
• Sanitation.
• Maintenance.
• Subpart D – Equipment
• Equipment design, size, and location.
• Equipment construction.
• Equipment cleaning and maintenance.
• Automatic, mechanical, and electronic equipment.
• Filters.
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16. 4. Laboratory Control System
• This system includes measures and activities
related to
1. Laboratory procedures
2. Testing
3. Analytical methods development
4. Validation or verification
5. The stability program
• Inspection is carry out according to the cGMP
regulation, 21 CFR 211 Subparts B, I, J, and K.
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17. 5. Materials System
• This system includes measures and activities to control
finished products components, including water or gases
that are incorporated into the product, containers and
closures.
• It includes :
• validation of computerized inventory control processes,
• drug storage,
• distribution controls, and records.
• Inspection is carry out according to the cGMP regulation,
21 CFR 211 Subparts B, E, H, and J.
• Subpart H - Holding and Distribution
• Warehousing procedures.
• Distribution procedures.
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18. • Component -Any ingredient intended for use in the
manufacture of a drug product, including those that
may not appear in such drug product, 21 CFR
210.3(b)(3) Ex. excipients, water, gases, etc., even if
not in final product
• Active Ingredient- Any component that is intended
to furnish pharmacological activity or other direct
effect in the diagnosis, cure, mitigation, or to affect
the structure or any function of the body of man or
other animal, 21 CFR 210.3 (b)(7)
• Inactive ingredient (excipient) -Any component
other than an active component, 21 CFR 210.3(b)(8)
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19. 6. Packaging and Labeling System
• This system includes measures and activities that
control the packaging and labeling of drugs and
drug products.
• It includes
• written procedures
• label examination and usage
• label storage and issuance
• packaging and labeling operations controls
• validation of these operations
• Inspection is carry out according to the cGMP
regulation, 21 CFR 211 Subparts B, G, and J.
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20. SELF INSPECTION
• The self inspection is one of the key factors in
pharmaceutical industry, to identify known and
unknown non-compliance of the process,
procedure, equipments, storage conditions, utilities
etc., and will be regularized as per the current
standard operating procedure or regulatory
requirements.
• This inspection will be conducted atleast once in a
year or frequency can be conducted initially once in
quarter or month based on the observations and its
control, self inspection must be conducted
in pharmaceutical industry with sub matter experts
of the respective area.
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21. • Each of the following guidelines describes the requirement of
self-inspection under the different chapters as below.
• WHO describes about the Self-inspection in Annexure 3:
• Schedule M describes about the Self-inspection in premises
Building and facilities of section 15.
• USFDA (United states of food and drug administration)
describes about the Self Inspection in PART 211- sub part B of
chapter I
• MHRA (Medicinal Health and Regulatory Agencies) describes
about the Self Inspection in Section II – 2EU Guidance on Good
Manufacturing Practice (GMP) – Self-Inspection
• TGA (Therapeutic Good and Administration)/PICS
(Pharmaceutical Inspection Convention/Pharmaceutical
inspection and cooperation scheme) describes about the Self
Inspection in CHAPTER 9 Quality Management Self-Inspection
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22. Objectives of Inspection
1. To detect and remove the faulty raw materials
before it undergoes production.
2. To detect the faulty products in production
whenever it is detected.
3. To bring facts to the notice of managers before
they become serious to enable them discover
weaknesses and overcome the problem.
4. To prevent the substandard reaching the customer
and reducing complaints.
5. To promote reputation for quality and reliability of
product.
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23. Purpose of Inspection
1. To distinguish good lots from bad lots.
2. To distinguish good pieces from bad pieces.
3. To determine if the process is changing.
4. To determine if the process is approaching the
specification limits.
5. To rate quality of product.
7. To measure the precision of the measuring
instrument.
8. To secure products-design information.
9. To measure process capability.
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25. • Benefits of self inspection
• The intent of self inspection is to identify the gaps
with approved procedure and current regulatory
requirements from subject matter expert along
with corporate team or from external agencies.
• The identified observations indicate the overall
performance of quality systems and procedures.
• These observations are discussed in the closure
meetings and compliance of those observations
through a CAPA tracking system has to be
undertaken to ensure that these observations are
assessed and closed in timely manner.
• Such practices will be helpful to give a confidence
to the team and management to face any
regulatory audits at any point of time. 25

26. • Hence any observations needs to be acted upon
priority and block the deviations in real time,
• This will create the healthy situation for the
organization, though initially will have lot of
brakes and hiccups , once it is streamlined will
get more output with better quality of the
product in the long run.
• All the inspections reports and its’ compliance
reports needs to be documented with supporting
evidences which help in monitoring the
effectiveness of the implemented CAPAs on
routine basis.
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27. Thank you
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