This document outlines the Six System Inspection Model used by the US FDA to inspect pharmaceutical manufacturing establishments. The six systems are: Quality System, Facilities and Equipment System, Materials System, Production System, Packaging and Labeling System, and Laboratory Control System. The model provides a comprehensive and organized framework to evaluate if establishments are complying with cGMP requirements across all key aspects of pharmaceutical production.

1. Six System Inspection Model
Prepared By-
Mr. Madane Vikram A
Department of Pharmaceutical Quality
Assurance
Bharati Vidyapeeth College of Pharmacy,
Kolhapur
Guided By-
Mr.Mahuli D.V
Department -pharmacology
Bharati Vidyapeeth College of Pharmacy,
Kolhapur

2. Contents
•US FDA Compliance Program.
•Objectives of the Program.
•Strategy for inspection.
•Six System Inspection Model.
•Summary.
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3. US FDA Compliance Program
 Until 2012, FDA used to inspect establishments in
United States for every two years but there was no
comparable requirement or any protocol for foreign
investment.
 So there was formation of The Food and Drug
Administration Safety and Innovation Act (FDASIA),
which amended the FD&C Act section 510(h),
eliminated this distinction, directing FDA to take a risk-
based approach to inspecting both domestic and foreign
drug manufacturing establishments.
 This compliance program provides surveillance
inspection coverage of drug manufacturing
establishments complying with the requirements of
CGMP as per 501(a)(2)(B) of the Act and implementing
regulations.
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4. Objectives of Compliance Program
 The goal of this program's activities is to ensure that
establishments consistently manufacture drug products of
acceptable quality and minimize consumers' exposure to
adulterated drug products.
 To determine whether establishments work according to
the given cGMP requirements and if not, to take actions
against the aduslterated products and to restrict them from
releasing.
 To assess the firms and to give input to firms to improve
the compliance with regulations.
 To better understand the manufacturing practices
according to cGMP, Regulatory policy, etc.
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5. Strategy for inspection
 As drug products are manufactured using various sets of
unit operations including physical till labelling for
distribution, it can be organised into various sets of
operations called as Systems.
 Control of all these systems helps ensure the firm will
produce drugs that are safe, have the identity and strength,
and meet the quality and purity characteristics as intended.
 Inspections of drug manufacturers should be made and
reported using the system definitions and industry codes in
this compliance program.
 Complete inspection of one system may necessitate further
follow up of some items within the activities of
another/other system(s) to fully document the findings.
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6. Six System of Inspection model
 For inspection of the establishments, under 21 CFR
211 following scheme of sytems known as six
system of inspection model was established.
 This rational scheme of set of six systems
incorporated the general scheme of pharmaceutical
manufacturing operations.
 This general scheme of systems for inspection
brought level of cGMP manufacturing practices
among the pharmaceutical companies and also
bringing a desired quality for the products.
 This system is inspected and documented by the
regulatory agency majorly by US FDA under
compliance program. 6

7. What are the Six Systems
1. Quality System.
2. Facilities and Equipment System.
3. Materials System.
4. Production System.
5. Packaging and Labeling System.
6. Laboratory Control System.
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8. Quality System
 This system assures overall compliance with CGMPs and
internal procedures and specifications. This system includes the
quality control unit and all of its review and approval duties.
 Carried out in two phase, whereas in first phase evaluation of
whether the Quality Control Unit has fulfilled the responsibility
to review and approve all procedures related to production,
quality control, and quality assurance and assure the procedures
are adequate for their intended use is done.
 Second phase is to assess the data collected to identify quality
problems which may link to other major systems for
inspectional coverage.
 The firm should have written and approved procedures and
documents which are inspected in this system.
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9.  Product reviews.
 Complaint reviews.
 Discrepancy and failure investigations related to
manufacturing and testing
 Change Control.
 Production improvement projects.
 Returns or Salvages.
 Stability failures.
 Validation.
 Training/qualification of employees in quality control unit
functions.
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10. Facilities and Equipment System
 This system ensures the appropriate physical environment
for the production of pharmaceutical products, such as;
buildings and facilities along with maintainance;
Equipment Qualification; Utilities which is not used
directly in product.
 There is a written and approved procedures for each thing
included in this system which should be followed strictly
according to cGMP guidelines such as SOPs, etc.
 When this system is selected for coverage in addition to
the Quality System, all areas listed further should be
covered; however, the depth of coverage may vary
depending upon inspectional findings.
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11.  Cleaning Maintainance.
 Cross contamination.
 General Air handling systems.
 Equipment installation,qualification,design,size and
location.
 Cleaning procedures and validation.
 Control systems.
 Appropriate use of equipment operations substances.
 Documented investigation into any unexpected
discrepancy.
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12. 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.
 These areas are not limited to finished products, but may
also incorporate components and in-process materials.
 Deficiency in this system may also affect the warrant
explosion of other systems.
 Following list should be considered:
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13.  Training and Qualification of personnel.
 Identification and inventory of components, containers
and closure.
 Storage conditions.
 Rejection of any of the above things.
 Quarantine of rejected materials.
 qualification/validation and security of computerized or
automated processes.
 finished product distribution records by lot.
 documented investigation into any unexpected
discrepancy.
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14. 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, and process validation.
 It also includes establishing, following, and documenting
performance of approved manufacturing procedures.
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15.  control system for implementing changes in processes
 adequate procedure and practice for charge-in of components
 formulation/manufacturing at not less than 100%
 identification of equipment with contents, and where
appropriate phase of manufacturing and/or status
 validation and verification of cleaning/sterilization/
depyrogenation of containers and closures
 calculation and documentation of actual yields and percentage
of theoretical yields
 contemporaneous and complete batch production
documentation
 adherence to preprocessing procedures (e.g., set-up, line
clearance)
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16. 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, and validation of these operations.
 acceptance operations for packaging and labeling
materials
 control system for implementing changes in
packaging and labeling operations
 adequate storage for labels and labeling, both
approved and returned after issued
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17.  control of labels which are similar in size, shape, and color
for different products
 finished product cut labels for immediate containers which
are similar in appearance
 gang printing of labels is not done, unless they are
differentiated by size, shape, or color
 control of filled unlabeled containers that are later labeled
under multiple private labels
 adequate packaging records that will include specimens of
all labels used
 control of issuance of labeling, examination of issued labels
and reconciliation of used
 labels
 examination of the labeled finished product
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18. Laboratory Control System
 This system includes measures and activities related to
laboratory procedures, testing, analytical methods
development and validation or verification,and the stability
program.
 adequacy of staffing for laboratory operations
 adequacy of equipment and facility for intended use
 calibration and maintenance programs for analytical
instruments and equipment
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19.  validation and security of computerized or automated
processes
 reference standards; source, purity and assay, and tests to
establish equivalency to current
 official reference standards as appropriate
 system suitability checks on chromatographic systems
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20. Summary
• Because of US FDA’s not a proper protocol for inspection, FDASIA
program was launched, which included six system inspection model.
• This model helped in auditing and inspecting premises of the firms or
establishments.
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21. THANK YOU
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