Pharmaceutical Inspections by various regulatory authorities

1. FDA Inspection of Manufacturing Sites
Guided By Presented By
Dr. S. J. Kshirsagar Mr. Sagar M. Nemade
Dr. G. S. Deokar M-pharm (Sem-1st)
Roll No - 13
QAT Department
MET’s Institute of Pharmacy
Adgaon, Nashik 422003
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2. Contents
 Definitions
 Objectives
 Pre-inspection process
 Strategies
 Inspection process
 System Inspection coverage
 Post-inspectional process
 Reporting
 Recent Inspectional News
 References
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3. Introduction
The Food & Drug Administration conduct the inspectional activities on the
manufacturing premises to check whether compounded, distributed drug & drug
products fulfill the requirements which are mentioned in the Federal Food, Drug, and
Cosmetic Act 501(a)(2)(B) . Following are the terms and their definitions regarding the
process
 Inspection
The inspection is defined as audit coverage of 2 or more systems, with mandatory coverage
of the Quality System. Inspection options include different numbers of systems to be
covered depending on the purpose of the inspection.
 Inspector/ Investigator
Any person designated who inspects the systems/subsystems for the purpose of the
enforcement of the FDA
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4. OBJECTIVES
 The goal of this program's activities is to minimize consumers' exposure to adulterated
drug products.
1) to determine whether inspected firms are operating in compliance with applicable CGMP
requirements
2) to provide CGMP assessment which may be used in efficient determination of
acceptability of the firm in the pre-approval review of a facility for new drug applications;
3) to provide input to firms during inspections to improve their compliance with regulations;
4) to continue FDA's unique expertise in drug manufacturing in determining the adequacy of
CGMP requirements
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5. FDA’s Inspection of manufacturing site
 A primary mission of the Food and Drug Administration is to conduct comprehensive
regulatory coverage of all aspects of production and distribution of drugs and drug
products to assure that such products meet the 501(a)(2)(B) requirements of the Act.
 FDA-trained auditors from Conformity Assessment Bodies and independent third
parties accredited by FDA works as an inspector/ investigator at the particular
manufacturing sites
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6. Pre-inspection process
 FDA calls domestic manufacturers about 5 days before the inspection
 FDA contacts foreign manufacturers 2 - 3 months in advance to schedule
inspection
 Manufacturer is requested to send Quality System Manual or equivalent for pre-
inspection review
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7. Strategies
 FDA has developed two basic strategies:
o Based on QSIT,
 1) evaluation through factory inspections, including the
collection and analysis of associated samples, the conditions
and practices under which drugs and drug products are
manufactured, packed, tested and held, and
 2) monitoring the quality of drugs and drug products
through surveillance activities such as sampling and
analyzing products in distribution.
GGUIDEUIDE TOTO IINSPECTIONSNSPECTIONS OFOF
QQUALITYUALITY SSYSTEMSYSTEMS
FOOD AND DRUG
ADMINISTRATION
August 1999August 1999
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8. Inspection process
 Biennial Inspection of Manufacturing Sites (includes repackaging, contract
labs, etc.)
 reduce the risk that adulterated products are reaching the marketplace;
 increase communication between the industry and the Agency;
 provide for timely evaluation of new manufacturing operations in the firm; and,
 provide for regular feedback from the Agency to individual firms on the continuing
status of the firm's GMP compliance.
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9. Inspection of Systems
o Scheme of systems for manufacture of Drug & Drug products
Scheme
of
Systems
Quality
System
Facilities &
Equipment
System
Materials
System
Production
System
Packaging
& Labeling
System
Laboratory
Control
System
.
 Consisting of,
 Quality System - Overall compliance
with cGMP’s and internal procedures
and specifications.
 Facilities and equipment system- The
measures and activities which
provide an appropriate physical
environment and resources used in
the production of the drugs
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10. 10
Material
system
Activities to control finished products, components,
including water or gases, that are incorporated into
the product, containers and closures.
Production
system
Measures to control the manufacture of drugs and
drug products including batch compounding, dosage
form production, in-process sampling and testing, and
process validation.
Activities that control the packaging and labeling of
drugs and drug products.
Packaging
and Labeling
system
Laboratory
system
Activities related to laboratory procedures, testing,
analytical methods development

11. System Inspection coverage :-
 Training/ Qualification of personnel in each systems
 Acceptance operations of the processes involved in particular systems
 Adequate storage conditions for each component of systems (e.g. equipment's , products,
raw materials, packaging and labeling materials, laboratory components)
 Thorough checking of every process conducted in particular system
 Maintenance of records (e.g. MPCR, BPCR)
 Rechecking, retesting and reexamination as well as quarantine of rejected and returned/
salvaged products
 Cleaning processes and log checking, cleaning validation
 Documented investigation into any unexpected discrepancy
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12. Post-inspectional process
 The investigator will ;
 Meet with management to discuss the inspection
 Present the FDA 483 list of observations
of any significant deficiencies
 Discuss the deficiencies and queries that
are observed
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13. Post-inspectional process………
 Investigator writes an “Establishment Inspection Report” or EIR
 Inspection report is classified based on inspectional findings
 Office of Compliance reviewer writes Warning Letter for inspection classified “OAI” if
found such deficiencies
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14. Manufacturer's work after inspection
 Send a letter to FDA identifying how they have corrected deficiencies or will
correct them
 Provide documentation of any corrections that have been completed
 Provide a timetable or estimated completion date for future corrections
 Assurance of completion or correction the deficiencies within time as he specified
in the letter
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15. Reporting
 The investigator will utilize Sub-chapter 590 of the IOM for guidance in reporting
of inspectional findings.
 Identify and explain in the body of the report the rationale for inspecting the
profile classes covered.
 Add additional information as needed or desired
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16. Recent inspectional activities by FDA
 Inspection conducted in October17,2015 on Theranos
inc.
 FDA announced revolutionary pinprick blood vials as
“unapproved medical devices.”
 As a result Theranos is halting work on its brand new
blood test technique
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17. References :-
 Guidelines :-
 Federal Food, Drug, and Cosmetic Act, as amended
 Code of Federal Regulations, Title 21, Parts 210 & 211
 Manuals :-
 Inspection operation manual (IOM)
 Guide to inspection of Dosage Forms Drug Manufacturers – CGMP’s
 Websites :-
 ORAHQDrugInspectionPOC@fda.hhs.gov
 http://www.fda.gov/ora/inspect_ref/igs/qsit/QSITGUIDE.pdf
 http://www.fda.gov/ora/inspect_ref/igs/qsit/qsitguide.html
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18. Thank you…18