2. Quality Assurance
Quality assurance is a wide ranging concept covering
all matters that individually or collectively influence the
quality of a product.
It is the totality of the arrangements made with the
object of ensuring that pharmaceutical products are of
the quality required for their intended use.
QA is the heart and soul of quality control
QA = QC + GMP
3. The System of Quality Assurance
Pharmaceutical products are designed and developed
in a way that takes account of the requirements of
GMP and other associated codes such as those of
good laboratory practice (GLP) and good clinical
practice (GCP)
Product and control operations are clearly specified in
a written form and GMP requirements are adopted
4. The System of Quality Assurance
Managerial responsibilities are clearly specified in
job description
Arrangements are made for the manufacture, supply
and use of the correct starting and packaging
materials.
All necessary controls on starting materials,
intermediate products, and bulk products and other
in-process controls, calibrations, and validations are
carried out.
5. The System of Quality Assurance
The finished products is correctly processed and
checked according to the defined procedures.
Pharmaceutical products are not sold or supplied
before the authorized persons have certified that each
production batch has been produced and controlled in
accordance with the requirements of the marketing
authorization and any other regulations relevant to the
production, control and release of pharmaceutical
products
6. The System of Quality Assurance
Satisfactory arrangements exist to ensure, as far as
possible, that the pharmaceutical products are stored
by the manufacturer, distributed and subsequently
handled so that quality is maintained throughout their
shelf-life.
There is a procedure for self-inspection and/or quality
audit that regularly appraises the effectiveness and
applicability of the quality assurance system
7. The System of Quality Assurance
Deviation are reported, investigated and recorded
There is a system for approving changes that may
have an impact on product quality
Regular evaluations of the quality of pharmaceutical
products should be conducted with the objective of
verifying the consistency of the process and ensuring
its continuous improvement.
9. Quality Assurance
It is the sum total of the
organized arrangements with
the objective of ensuring that
products will be of the
quality required for their
intended use
10. Good Manufacturing Practice
Is that part of Quality
Assurance aimed at ensuring
that products are consistently
manufactured to a quality
appropriate to their intended
use
11. Good Manufacturing Practice
GMP Covers all aspects of production including
• Raw or starting materials
• Finished products
• Premises and environment
• Equipment
• personnel
• Training
• Hygiene
12. Quality System
with Traceable
Documentation Approved
Materials
Approved
Manufacturing
Instructions
Controlled
Environment
Controlled Materials
Handling, Storage,
Segregation,
Packaging &
Labelling
Material,
Intermediate
& Finished
Products
Testing
Internal
Audits &
Reviews
Validated Test
Method
Validated
Manufacturing
Processes
Validated
Equipment
Approved
Manufacturing
Facilities
Trained
Personnel
GOOD
MANUFACTURING
PRACTICE
13. Quality Control
Is that part of GMP concerned
with sampling, specification
& testing, documentation &
release procedures which
ensure that the necessary &
relevant tests are performed
& the product is released for
use only after ascertaining
it’s quality
14. QA and QC
QC is that part of GMP
which is concerned with
sampling,
specifications, testing and
with in the organization,
documentation,and
release procedures which
ensure that the necessary
and relevant tests are
carried out
• QA is the sum total of
organized
arrangements made
with the object of
ensuring that product
will be of the Quality
required by their
intended use.
15. QA and QC
Operational
laboratory techniques
and activities used to
fulfill the requirement
of Quality
• All those planned or
systematic actions
necessary to
provide adequate
confidence that a
product will satisfy
the requirements for
quality
16. QA and QC
QC is lab based
• QA is company
based
17.
18.
19. Quality Assurance-Highlights
In process quality checking in manufacturing
Validation of facilities, equipments, process,
products and cleaning
Complaint handling
Storage of quality records and control samples
Stability studies
20. Quality Assurance Activities
1. Technology Transfer
2. Validation
3. Documentation Control
4. Assuring Quality of Products
5. Quality Improvement Plans
21. 1. Technology Transfer
Receipt of product design documents from R & D
Department
Distribution of documents to different departments
Checking and approval of documents generated based
on R & D documents i.e. batch manufacturing record
Scale‐up and validation of product
22. 2. Validation
• Preparation of validation plans
equipments/process including cleaning
for facility,
• Approval of protocol for validation of facility
/equipment /product /process
• Team member for execution of validation of
facility/equipment/ product/process
23. 3. Documentation Control
Controlled distribution and archiving of documents
Control of changes made by proper change control
procedure
Approval of all documents
24. 4. Assuring Quality of Products
cGMP training
SOP compliance
Audit of facility for compliance
Line clearance
In‐process counter checks
Critical sampling
Record verification
Release of batch for marketing
Investigation of market complaints
25. 5. Quality Improvement Plans
To take Feedback from different departments
Proposals for corrective and preventive actions
Annual Products review
Trend analysis of various quality parameters for
products, environment and water
26. FACTORS IN DRUG QUALITY ASSURANCE
DRUG
PRODUCT
QUALITY
Labeling &
Product
Information
Import
& Export
Control
Raw
Materials-
Active &
Inactive
Manufacturing
Processes
& Procedures Storage
Transport
Distribution
Dispensing
& Use
QC &
Analysis
Human
Resources-
Professionals
Legislative
Framework
-Regulations Packaging
28. Quality Assurance
Highlights
• In process quality checking in manufacturing
• Validation of facilities, equipments, process,
products and cleaning
• Complaint handling
• Storage of quality records and control
samples
• Stability studies
29.
30. Equipment /Instrument Qualification
Before a process can be validated the equipment,
facilities & services used in that process must
themselves be validated such an operation is referred
to as qualification
Qualification therefore, an integral part of process
validation which in turn is part of GMP
33. Why to qualify
According to GLP, cGMP, GAMP, ISO 9000 etc.
If the instrument is not qualified prior to use & if a problem
occurs, the source of problem will be difficult to identify.
Qualification is the part of validation
Begins at Vendor’s site
Structural Validation
Design/Development stage of equipment/instrument
Produced in validated environment
34. Qualification Involves
Performance Qualification (PQ)
User Requirement Specification (USR)
Functional Design Specification (FDS)
Design Qualification (DQ)
FactoryAcceptance Tests (FAT)
Installation Qualification (IQ)
Site Acceptance Test (SAT)
Operational Qualification (OQ)
35. Details Record in Change Control
Request for change
Change control No.
Date
Change related to
product/document/system/facility
Concerned documents with number
Description of change
Reason for change
Impact of change
36. Details Record in Change Control
Proposed methodology for implementation
Category of change
Type of change
Comparison criteria for evaluation of the
change
Assessment of impact of change
Approval of change
Implementation of change
Closure of change
37. Details Recorded in Deviation Approval
Deviation no.
Deviation related to
Concerned identity number (Batch No., Code No. etc)
Type of deviation (Planed/Unplaned)
Description of deviation
Reason/Investigation with document
Category of deviation
Root cause analysis
38. Details Recorded in Deviation Approval
Impact of deviation (on batches, Products, Items, etc)
Immediate action
CAPA (Corrective and PreventiveAction)
Impact of CAPA
Intimation to concerned
Comments from concerned
Periodic review
Final review
Deviation close-out
Evaluation of implemented CAPA
39. Details Recorded In Out of Specification Report
OOS No. (Out of Specification)
Reporting of OOS
Information of OOS to immediate senior
Assessment of analytical data by immediate senior
Discussion between analyst and immediate senior
Sampling and analysis
Data compilation
Assignable cause identification
Full scale OOS investigation (Cause not identified)
Evaluation
Conclusion
CAPA
OOS results summary
40. Area of Self Inspection
Personal & Personal details
Premises including personnel facilities
Maintenance of building & equipment
Storage of starting material & finished products (Stores)
Equipment
Production & In-process controls
Cephalosporin Mfg & Packing
Manufacturing
Packing
Quality control
Documentation
Sanitation & Hygiene
Validation and revalidation program
41. Areas of Self Inspection
Calibration of instruments or measurement system
Recall procedure
Complaints management
Labels control
Computerized system
Engineering
Documents related to regulatory affairs
Discarding of residues
Quality assurance
Control on contract analysis
Results of previous self inspection, quality audit and any
corrective steps taken
42. Details Recorded in Complaint Investigation Report
Complaint No.
Product Name
Manufacturing and Expiry of product
Source of complaint
Date of receipt of complaint
Nature of complaint
Category of complaint
43. Details Recorded in Complaint Investigation Report
Investigation
Impact of complaint on other batches/products
Batches/Products
Review
CAPA
Impact of CAPA
Implementation of Preventive action
Close out of complaint
44. Acceptance Criteria
Sr. No. RPN Rating RPN Category
1. Up to 25 Minor
2. 26 to 50 Moderate
3. 51 to 75 Major
4. 76 to ≤125 Critical
RPN: Risk Priority Number
48. Regulatory Requirements
Regulatory requirements are part of the process of drug
discovery and drug development.
Regulatory requirements describe what is necessary for a new
drug to be approved for marketing in any particular country.
In the US, it
Administration
requirements.
is the function of the
(FDA) to establish
Food and Drug
these regulatory
The European Medicines Agency (EMA) and
Japanese Pharmaceuticals and Medical Devices Agency
(PMDA) are also important regulatory authorities in drug
development. These three agencies oversee the three largest
markets for drug sales
49. Regulatory Compliance
In general, compliance means conforming to a
rule, such as a specification, policy, standard
or law.
Regulatory compliance describes the goal
that corporations or public agencies aspire to
in their efforts to ensure that personnel are
aware of and take steps to comply with
relevant laws and regulations.
50. Pharmaceutical Product Quality Cannot Be Tested in - It
Is Built in
Pharmaceutical product quality is assured by
Comprehensive development program
Extensive manufacturing and environmental
controls
Rigorous validation procedures and
requirements
Compliance to regulatory requirements
The high quality thus built into the final product is ensured through
in-process controls and verified in a series of confirmatory tests
before each manufactured batch is released to the market
51. Quality = Quality of Manpower (Qualification, Training…)
+ Quality of Materials (Specifications, Approved Suppliers...)
+ Quality of Means (Qualified equipments, maintenance…)
+ Quality of Media (GMP premises, Controlled environment…)
+ Quality of Methods (Calibration, Validation…)
Product / Service
Materials
Methods
Means
Manpower
Media
Composition of Quality
52. Functions of a Quality Unit
Quality Control
–Sampling and testing of components
(raw materials, Packing materials),
intermediates and finished products
–Compliance to Good Laboratory
Practices (GLPs)
53. Functions of a Quality Unit
Quality Assurance
–Designing robust quality
systems
–Ensure compliance to
relevant regulatory
requirements
–Ensure compliance to
requirements of Good
Manufacturing Practices
(GMP)
54. Value addition in QA function
Quality Assurance:
–Perform structured self-
inspection audits at regular
intervals to prevent any
failure or non-conformance
–Critically analyze the quality
non-conformance issues and
suggest corrective and
preventive actions
55. Value addition in QA function
Quality Assurance:
–Perform documentation
audit to ensure realistic
recording of all the relevant
process parameters
–Review the adequacy of in-
process control checks to
prevent any potential
failures
56. Value addition in QA function
Quality Assurance:
– Training & Knowledge Management
– Perform literature survey of FDA /
ICH / ISO guidelines, revisions in
the Pharmacopoeial specifications
and the current regulatory
requirements and provide training to
the production personnel.
57. Value addition of Regulatory function to enhance Quality
Assurance
Regulatory Compliance:
–Knowledge of the current
international regulatory
requirements
–Comprehensive compilation of
the ‘Product Registration
Dossiers’ for the specific
customer countries
60. National (India)
License Application Receipt
Manufacturing license Form No. 24 Form No. 25
Test license Form No. 30 Form No. 29
Import license Form No. 12 Form No.11
Compliance to (Drugs & Cosmetics Act 1940 & Rules under)
61. National (India)
Drug Regulatory
approval
Schedule Y Compliance
Form 44
Manufacturing Schedule M Compliance
Documentation Schedule U Compliance
Packaging Schedule P Compliance
API/Excipients/FP/PM IP Inputs if not BP/USP/ or IH
62. Regional (US)
Parameters US
API USP (US DMF Type II)
Excipients USP
Packaging materials Complying to USP (Type III DMF)
Finished Product USP
Submission batch 1
Submission batch size 100,000 units or 1/10th of commercial batch
Stability Zone II requirement
25º+2ºC/60+5%RH & 40º+2ºC/75+5%RH
Reference product US RLD (Orange book listed)
Bioequivalence study Generally both fast & fed condition
Compliance to 21 CFR and its sub parts such as part 210 – 211, part 11,
part 314, part 350, ICH etc.,
Generic application FDA form 356h
63. Regional (Europe)
Parameters Europe
API Ph.Eur. [COS (CEP) / EDMF]
Excipients Ph.Eur.
Packaging materials Ph.Eur.
Finished Product As per Ph.Eur. General requirement
Submission batch 2
Submission batch size 100,000 units or 1/10th of commercial batch
Stability Zone II requirement
25º+2ºC/60+5%RH & 40º+2ºC/75+5%RH
Reference Product Europe
Bioequivalence study Generally fasting condition
Compliance to Orange guide, EDQM, CHMP, CPMP guidelines, ICH
Generic application AS per Article 10 and its sub sections
64. Regional (Others)
Parameters Other markets
API USP / Ph.Eur. (DMF requirement depends on the target
market)
Excipients USP / Ph.Eur.
Packaging materials USP / Ph.Eur.
Finished Product USP / Ph.Eur.
Submission batch 2 or 3
Submission batch size Depends on the target market
Stability Depends on the Target market (E.g.: ASEAN: Zone IVb)
Reference Product Depends on the Target market
Bioequivalence study Generally fasting condition
Compliance to Respective country guidelines
Generic application AS per respective country guidelines
65. Global
Parameters Global
API Harmonization of specification
Excipients Harmonization of specification
Packaging materials Harmonization of specification
Finished Product Harmonization of specification
Submission batch 3
Submission batch size 100,000 units or 1/10th of commercial batch
Stability Zone III & IV
Reference Product Multiple region
Bioequivalence study Fasting & Fed condition
Compliance to Global Standards
Generic application AS per respective country guidelines
66. Regulatory Dossier
CTD dossier component
Module 1- Administrative & prescribing information (Region
specific)
Module 2: CTD summaries (Quality overall summary, the non-clinical
overview/summaries, clinical overviews/Summaries)
Module 3: Quality (CMC)
Module 4: Non clinical study reports (Documentation on
Toxicological and pharmacological tests)
Module 5: Clinical study reports (For Generics: Bioequivalence
study)
CTD ORGANIZATION IS BASED ON
M4: Organization of the CTD
M4E: The CTD — Efficacy
M4Q: The CTD — Quality
M4S: The CTD — Safety
67.
68. Regulatory Dossier
Regulatory approach:
Parameters US Europe Other markets India
API USP Ph.Eur. USP / Ph.Eur. IP
USDMF COS (CEP) / EDMF DMF requirement
depends on the
target market
Excipients USP Ph.Eur. USP / Ph.Eur. IP
Reference product US Europe Depends on the
target market
Indian (if not
available, then
US or Europe)
Packaging
materials
Complying to USP Ph.Eur. USP / Ph.Eur. IP
Finished product USP As per Ph.Eur.
General requirement
USP / Ph.Eur. IP
Submission batch 1 2 2 or 3 -
Submission batch
size
100,000 units or
1/10th of commercial
batch
100,000 units or
1/10th of
commercial batch
Depends on the
target market
No such
requirement
69. Regulatory Dossier
Regulatory approach:
Parameters US Europe Other markets India
Stability data 1 batch 2 batches 2 or 3 batches 3 batches
Stability condition Zone I & II condition Zone I & II condition Depends on the
target market
Zone IV condition
Comparative
dissolution study
3 media 3 media Depends on the
target market
1 to 3 media
Input materials TSE/BSE, OVI
statements
TSE/BSE Depends on the
target market
No such requirement
Packaging materials Food grade certificate Food grade certificate Depends on the
target market
No such requirement
Method validation data As per ICH ICH ICH No such guideline
Process validation
data
Not required Not required Depends on the
target market
Not required for
submission
Bioequivalence study US reference product
under fast and fed
condition
European reference
product (generally
under fasting condition)
Generally fasting bio
study
Fasting bio study
Bioequivalence study In USFDA approved
CRO anywhere in the
world
MHRA/EU approved
CRO anywhere
Depends on the
target market
Indian study required
70. Specific requirements of an US ANDA
QOS: in QbR format (Quality overall summary:Question-based review)
Exhibit batches (1 batch)
Stability data at the time of submission (3 Months)
TSE/BSE certificate (Transmissible spongiform encephalopatics/Bovine spongiform encephalopathy)
Structured Product Labeling (SPL) & side by side labeling comparison
OVI statement (Organic volatile impurities)
Financial certification / disclosure statement (Bioequivalence study)
Environmental assessment or claim for categorical exclusion
Declaration under Generic Drug Enforcement Act (Debarment certification & conviction statement)
Patent certification & exclusivity statement
Appointment of US agent & letter of US agent authorization
Copy of executed batch records
71. Specific requirements of an EU dossier
Release testing in EU (QP)
Exhibit batches (2 batches)
Stability data (6 Months)
Process validation study
Release and shelf life specification
Microbiological considerations
TSE/BSE certificate
SPC (Summary of product characteristics)
Braille labeling (Just another way to read and write English)
Readability testing
72. Regulatory Approval
Product Approval / Authorization
Successful registration of the product in the target market involves:
Successful review of API DMF / COS
Successful audit of API plant (wherever applicable)
Successful review of Drug Product Dossier (ANDA, MAA etc.)
• CMC data review
• Bioequivalence study data review
• Administrative data review
Successful audit of the drug product manufacturing plant
Successful audit of the bioequivalence study CRO
73. Quality Assurance: Common Regulatory Compliance Issues
API
Infringing route of synthesis
Not consistent with respective Pharmacopoeial requirement
Impurity profile out of limit
Residual solvents not meeting the requirements
Unapproved site of manufacture (by concerned regulatory body)
Unacceptable physico-chemical properties (particle size, polymorphism, bulk
density, etc.)
From manufacturer who does not assure uninterrupted supply of API
Unapproved vendor (by drug product manufacturer)
Use of non DMF / COS material (e.g.: US, Europe etc.)
High cost (commercial viability)
74. Excipient
Use of rarely available / or commonly not used excipients
Use of Non GRAS materials (Generally recognized as safe)
Incompatible
Not consistent with respective Pharmacopoeial requirement
Residual solvents not meeting the requirements
TSE / BSE / GMO (Genetically modified organisms)
Unapproved vendor
Unacceptable physico-chemical and functional properties (particle size,
bulk density, viscosity grade, surface area, degree of polymerization etc.)
From manufacturers who do not assure uninterrupted supply
High cost (commercial viability)
Quality Assurance: Common Regulatory Compliance Issues
75. Formulation development
Pre-formulation
Improper API characterization
• Intrinsic solubility
• pH dependent solubility
• Saturation solubility
• Particle size
• Polymorph
• Bulk density
• Hygroscopicity study
• Impurity profile etc.,
Wrong choice of reference product (e.g. Not selecting innovator product)
Reference product not matching with the proposed market (e.g.: European
product selected for US market)
Inadequate drug excipient compatibility studies
Quality Assurance: Common Regulatory Compliance Issues
76. Formulation development
Use of overages without proper justification
Use of banned / unapproved colours (in target market)
Use of excipients without proper justification (e.g.: surfactants etc.)
Use of excipients not consistent with the proposed route of administration
Use of Pharmacopoeial grade not consistent with the target market
Infringing process
Lack of proper development report
Inadequate optimization study data on process controls
Complex / costly process / lengthy operating cycle
Use of non-aqueous solvents (to be avoided)
Quality Assurance: Common Regulatory Compliance Issues
77. Quality Assurance: Common Regulatory Compliance Issues
Formulation (Finished product)
Dissolution profile not matching with the reference product
Dissolution profile not matching with the bio strength in case of multi
strength products (for bio waiver purpose)
Not meeting Pharmacopoeial requirement
Dissolution – Lack of justification for selection of:
• Media
• Apparatus
• RPM
• Volume of media
• Sampling point
• Dissolution limit
• Justification for addition of surfactant (e.g.: SLS), enzymes (e.g.:
Pepsin, Pancreatin etc.) in the dissolution medium
78. Quality Assurance: Common Regulatory Compliance Issues
Formulation (Finished product specification)
Not meeting Pharmacopoeial requirement / ICH Q6A
Lack of second identification test (for non specific test)
Inadequate impurities & residual solvent specification (ICH Q3A, B,
Q3C)
Lack of testing for preservatives, anti-oxidants wherever used
Lack of test for breakability / content uniformity for half tablets
(when functional score line exists)
Lack of test for establishing polymorphic conversions
Color identification test (e.g.: Europe)
Test for water content in solid dosage form (e.g.: US)
Missing of microbiological tests
Lack of specification for testing after reconstitution
79. Quality Assurance: Common Regulatory Compliance Issues
Packaging Materials
Improper justification for the selection of packaging
materials
Lack of data on release / sorption / leaching study
(specially for those used in liquid / parenteral
preparations)
Lack of study to demonstrate integrity of container
closure system (where applicable)
Primary packaging material not suitable for its intended
performance (e.g.: child resistant)
Lack of identification test in the specification
Lack of food grade certification for the materials
Non use of virgin grade polymers
80. Quality Assurance: Common Regulatory Compliance Issues
Manufacturing of submission batches
Inadequate batch size (e.g.: less than 100,000 units or
1/10th of the commercial batch size whichever is higher)
Inadequate number of batches (e.g.: minimum 1 batch for
US, 2 batches for Europe etc.)
Inadequate packaging quantity (e.g.: minimum 100,000
units packed quantity for US)
Lack of process validation (applicable to many Asia Pacific
countries)
Lack of stratified sampling during in-process test (e.g.: US)
Hold time study
81. Quality Assurance: Common Regulatory Compliance Issues
Analytical methods
Analytical methods not validated
Analytical methods not stability indicating (for stability
studies)
Forced degradation studies not performed
Inadequate justification for choice / selection of method
(UV vs HPLC)
Inadequate justification for selection of conditions
(column, wavelength, run time, mobile phase, flow rate,
temperature etc.)
Non availability of method development report
In adequate method validation parameters (e.g.: LOD,
LOQ in RS method)
82. Quality Assurance: Common Regulatory Compliance Issues
Stability Study
Inadequate batch size (e.g.: less than 100,000 units or 1/10th
of the commercial batch size whichever is higher)
Inadequate number of batches (e.g.: minimum 1 batch for
US, 2 batches for Europe etc.)
Chamber temperature and humidity condition not appropriate
to the target market (e.g.: Zone I & II and Zone III and Zone
IV conditions are different)
Inadequate data at the time of submission (e.g.: 3 months
data for US, 6 months data for Europe)
83. Quality Assurance: Common Regulatory Compliance Issues
Stability Study
Photo stability study not considered
Improper container orientation (specially for
liquid products)
Inadequate stability study on bulk shipment
pack (if intended to ship it for repackaging)
Inadequate parameters covered under stability
protocol (e.g.: microbial testing)
Not charging samples under fall back condition
84. Stability
Global climatic zones
Zone
Mean Kinetic
Temperature (ºC)
Yearly average RH
(%)
Zone I (Moderate) 21 45
Zone II (Mediterranean) 25 60
Zone III (Hot & Dry) 30 35
Zone IV (Hot & humid) 30 70
85. Stability
Distribution of nations into different climatic
zones:
Region Zones I & II Zone III & IV
European All countries -
American Chile, Canada, United States
Brazil, Jamaica,
Venezuela
Asian China, Japan, Turkey
India, Philippines, Sri
Lanka
African
South Africa, Zambia,
Zimbabwe
Botswana, Ghana,
Uganda
Australian / Oceanic Australia, New Zealand Fiji, Papua - New Guinea
86. Quality Assurance: Common Regulatory Compliance Issues
Bioequivalence study
Use of wrong strength (in case of multiple strength products)
Use of inappropriate reference product (e.g.: US reference product
for Europe study)
Inadequate number of volunteers
Inadequate sampling intervals to capture tmax / cmax (maximum time
points should be there around the expected tmax/cmax)
Inadequate wash out period
Design fault in deciding what to test (e.g. testing of parent
compound or active metabolite or both)
Choice of study (Fast / Fed study or both)
87. Quality Assurance: Common Regulatory Compliance Issues
Bioequivalence study
Use of non validated method for testing
Stability of plasma samples not established
Inadequate number of reserve samples (e.g.: 5 times of the sample
required for complete analysis)
Use of unapproved CRO
Inappropriate documentation [IEC / IRB approval of protocol, informed
consent, CRF, pharmacokinetic data, statistical data (SAS), etc]
Bioequivalence study sample formula different from commercial batch
formula
Bioequivalence study samples are not from GMP pivotal batch
88. Quality Assurance: Common Regulatory Compliance Issues
Regulatory audits
Training of personnel
Facility upkeep
Equipment upkeep and preventive maintenance program
Area and environmental monitoring
QA systems, documentation control and traceability
Vendor approval procedure
Inventory control and storage
Change controls, deviations
OOS
89. Quality Assurance: Common Regulatory Compliance Issues
Regulatory audits
Qualification / validation of system, facility, equipment etc.
Water system
HVAC system (Heating, ventilation and air conditioning)
Stability program
Process validation
Laboratory control, testing and release of materials
Documentation review (Batch records, analytical records, etc.)
Batch release by QA
90. Quality Assurance in Life Cycle Management
Tasks to be performed
Pharmacovigilance
Safety reports
Post Approval Changes / Variations
To implement necessary up-dates and changes of the dossier
Line extensions (major changes, requiring new MAA)
To implement necessary up-dates and changes of the dossier
Renewal / Re-registration
91. Quality Assurance in Life Cycle Management
Post Approval Changes
Formula
Batch size
Process
Site Change
Equipment Change
Source / Spec & test procedure
API / Excipients / Pkg Materials
Multiple Changes
92. Quality Assurance in Life Cycle Management
Post approval changes Reporting
Level 1 Annual Report
Level 2
Changes Being Effected (CBE)
Changes Being Effected in 30 days (CBE-30)
Level 3
"Scale-Up and Post-Approval Changes"
Changes Being Effected (CBE)
Changes Being Effected in 30 days (CBE-30)
Prior Approval Supplement (PAS)
Post Approval Changes (US SUPAC)
93. Quality Assurance in Life Cycle Management
Category Reporting
Minor Type 1A
Moderate Type 1B
Major Type II standard
Critical Type II complex
Post Approval Changes (Europe)
94. Quality Assurance in Life Cycle Management
Other markets India
Notifications e.g. Australia
Part A: Non-assessable changes
Part B: Self-assessable changes
Part C: Changes requiring approval
No such requirement
Post Approval Changes (Other markets)
95. Quality Assurance in Life Cycle Management
Registration validity
US: Annual report every year
Europe: Re-registration once in 5 years
India: License renewal every 5 years
Other countries: Generally 5 years
96. Quality Assurance: The most important element of regulatory
compliance
The most important element for compliance is…..
Manpower … Manpower … Manpower
It is the people who ensure Regulatory compliance at
every stage of product life cycle i.e. starting from
product development to life cycle management
The best way to enhance their capability is through …….
Training…….Training ……. Training
97. Quality Assurance: The state of compliance
Everything is likely to undergo change during the life
cycle of a product…….
Formula, Process, Equipment, Batch size, Suppliers,
Manufacturing site, Trade dress, Indications,
Regulatory requirements, Specifications & test
procedures, People and so on ………
The only thing that can not be changed is the….
“State of Compliance”
98. Regulatory Authorities
India: DCGI & State Drug Administration
European Union: EMEA and national
USA : Food and Drug Administration (FDA)
Australia : Therapeutic Goods Administration
Newzeland : Medsafe
South Africa: Medicines council control
Japan : Ministry of Health & Labour Welfare
Switzerland : Swissmedic
Brazil : ANVISA (The National Health SurveillanceAgency)
Mexico: COFEPRIS (The Federal Commission for the Protection against Sanitary Risk)
Chile : ISP - Instituto de Salud Pública de Chile
Columbia: INVIMA – Instituto Nacional de Vigilancia de Medicamentos
Alimentos Carrera 68 D No. 17 - 11 / 21
Argentina: ANMAT - set in 1992 Argentine National Administration of
Drugs, Food & Medical Technology
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: Federal Institute for Drugs and Medical Devices
