cGMP Vs GMP

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Good Manufacturing Practice Guidelines ICH Q7A
Presented by Malangsha
S shkrahul42_at_gmail.com
cGMP Vs GMP
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cGMP Vs GMP
It is my understanding that , Ultimately GMP
cGMP both the aim is same, means to prevention
of the product from bad quality entering the
market to endover peoples's life.  GMP applies to
pharmaceutical and healthcare products and help
to maintain high standards in these
products.  cGMP is to remind accepting countries
that all guidelines must be followed with latest
and current production processes i.e employ
technologies and systems which are
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cGMP Vs GMP
up-to-date in order to comply with the
regulation. FDA (Food and Drug Administration)
included the word current to ensure that
regulated firms use the most current Good
Manufacturing Practices (I believe that some
firms would actually use outdated versions of the
GMPs to manufacture regulated products. (the
FDA have made their standards
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cGMP Vs GMP

• immediately identifiable i.e cGMP Other
  international bodies such as the ICH, WHO use the
  term GMP, as do Canada, Japan and the EMEA
  (European authority). In FDA view cGMP means
  following 21 CFR 210 and 211 and no other.)

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Objective of

• To produce products conforming to
• predetermined specification
• To produce Product of consistent quality
• To minimize contamination

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What do mean by API
Any substances or mixture of substances intended
to be used in the manufacture of drug (medicinal)
product and that, when used in the production of
a drug, becomes an active ingredient of the drug
product. Such substances are intended to furnish
pharmacological activity or other direct effect
in the diagnosis, cure, mitigation, treatment, or
prevention of disease or to affect the structure
and function of the body.
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Regulatory Agencies
International Conference on Harmonization. This
consist of EU, US and Japan.
The United States Food and Drug Administration
European Directorate of Quality Medicines
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ICH Modules
Q1 - Stability testing
Q2 Validation of Analytical Procedures
Q3 Impurities
Q4 Evaluation Pharmacopoeia Texts
Q5 Biotechnology Products
Q6 Specifications
Q7 Good Manufacturing Practices
Q8 Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
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QUALITY MANAGEMENT
Principles
Quality should be the responsibility of all
persons involved in manufacturing.
Responsibilities of the Quality Unit(s)
involved in all quality-related matters.
review and approve
Establishing a system to release packaging and
labeling materials
Performing product quality reviews
Internal Audits (Self Inspection)
Regular internal audits should be performed in
accordance with an approved schedule.
Document audit findings and corrective actions
Agreed corrective actions should be completed in
a timely and effective manner.
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QUALITY MANAGEMENT
Responsibility for Production Activities
The responsibility for production activities
should be described in writing
All deviations are reported and critical
deviations are investigated and the conclusions
recorded
production facilities are clean and when
appropriate disinfected
the necessary calibrations are performed and
records kept
validation protocols and reports are reviewed and
approved
new and, when appropriate, modified facilities
and equipment are qualified.
Product Quality Review
Regular quality reviews of APIs should be
conducted with the objective of verifying the
consistency of the process.
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PERSONNEL
Personnel Qualifications
There should be an adequate number of personnel
qualified by appropriate education, training
and/or experience to perform and supervise the
manufacture of intermediates and APIs.
Personnel Hygiene
should practice good sanitation and health
habits.
should avoid direct contact with intermediates or
APIs.
Personnel suffering from an infectious disease or
having open lesions on the exposed surface of the
body should not engage in activities that could
result in compromising the quality of APIs.
Consultants
Consultants should have sufficient education,
training, and experience, or any combination
thereof, to advise on the subject
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BUILDINGS FACILITIES
Buildings and facilities should be
Located, Designed, and Constructed to facilitate
cleaning, maintenance, and operations as
appropriate to the type and stage of manufacture
minimize potential contamination.
designed to limit exposure to objectionable
microbiological contaminants
Utilities should be
Qualified and appropriately monitored
action should be taken when limits are exceeded..
Drawings for these utility systems should be
available
Water should be
Water used in the manufacture of APIs should be
demonstrated to be suitable for its intended use.
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BUILDINGS FACILITIES
Containment
Dedicated production areas, air handling
equipment and/or process equipment, should be
employed in the production of highly sensitizing
materials, such as penicillins or cephalosporins.
Lighting should be
Adequate lighting should be provided in all areas
to facilitate cleaning, maintenance, and proper
operations.
Sewage should be
disposed of in a safe, timely, and sanitary
manner. Containers and/or pipes for waste
material should be clearly identified.
Sanitation and Maintenance
Buildings should be properly maintained and
repaired and kept in a clean condition and
establish written procedures
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PROCESS EQUIPMENT
Design and Construction
Equipment should be of appropriate design and
adequate size, and suitably located for its
intended use
Equipment Maintenance and Cleaning
preventative maintenance of equipment.
Written procedures should be established
Cleaning procedures should contain sufficient
details to clean each type of equipment in a
reproducible and effective manner
Equipment should be identified as to its contents
and its cleanliness status
Acceptance criteria should be defined and
justified.
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PROCESS EQUIPMENT
Calibration
Control, weighing, measuring, monitoring and test
equipment that is critical for assuring the
quality of intermediates or APIs should be
calibrated according to written procedures and an
established schedule.
Computerized Systems
GMP related computerized systems should be
validated
installation qualification and operational
qualification should demonstrate the suitability
to perform assigned tasks
Computerized systems should have sufficient
controls to prevent unauthorized access or
changes to data.
Changes to the computerized system should be made
according to a change procedure
If system breakdowns or failures would result in
the permanent loss of records, a back-up system
should be provided.
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DOCUMENTATION RECORDS
Documentation System and Specifications
All documents related to the manufacture of
intermediates or APIs should be prepared,
reviewed, approved and distributed according to
written procedures. Such documents can be in
paper or electronic form.
Equipment Cleaning and Use Record
Records of major equipment use, cleaning,
sanitization and/or sterilization and maintenance
should show the date, time (if appropriate),
product, and batch number of each batch processed
in the equipment, and the person who performed
the cleaning and maintenance.
Raw Material Records
Records should be maintained including name,
identity, quantity name of the supplier
supplier's control number(s), the number
allocated on receipt date of receipt
Master (approved) labels should be maintained for
comparison to issued labels.
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DOCUMENTATION RECORDS
Master Production and Control Records)
To ensure uniformity from batch to batch, master
production instructions for each intermediate and
API should be prepared, dated, and signed by one
person and independently checked, dated, and
signed by a person in the quality unit(s).
Batch Production and Control Records)
Batch production records should include complete
information relating to the production and
control of each batch.
These records should be numbered with a unique
batch or identification number, dated and signed
when issued.
Documentation of completion of each significant
step in the batch production
Laboratory Control Records
Laboratory control records should include
complete data derived from all tests conducted to
ensure compliance with established specifications
and standards, including examinations and assays,
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MATERIAL MANAGEMENT
General Controls
There should be written procedures describing the
receipt, identification, quarantine, storage,
handling, sampling, testing, and approval or
rejection of materials.
should have a system for evaluating the suppliers
of critical materials.
Changing the source of supply of critical raw
materials should be treated according to Change
Control.
Receipt and Quarantine
each container or grouping of containers of
materials should be examined visually
Materials should be held under quarantine until
they have been sampled, examined or tested as
appropriate, and released for use.
Each container or grouping of containers
(batches) of materials should be assigned and
identified with a distinctive code, batch, or
receipt number.
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MATERIAL MANAGEMENT
Sampling and Testing
Sampling should be conducted at defined locations
Containers from which samples are withdrawn
should be marked to indicate that a sample has
been taken.
At least one test to verify the identity of each
batch of material should be conducted,
A supplier's Certificate of Analysis can be used
in place of performing other tests
Storage
Materials should be handled and stored in a
manner to prevent degradation, contamination, and
cross-contamination.
Rejected materials should be identified and
controlled under a quarantine system
Re-evaluation
Materials should be re-evaluated as appropriate
to determine their suitability for use
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PRODUCTION AND IN-PROCESS CONTROLS
Production Operations
Raw materials for intermediate and API
manufacturing should be weighed or measured under
appropriate conditions that do not affect their
suitability for use.
The processing status of major units of equipment
should be indicated either on the individual
units of equipment
Materials to be reprocessed or reworked should be
appropriately controlled to prevent unauthorized
use.
Time Limits
time limits should be met to ensure the quality
of intermediates and APIs
Intermediates held for further processing should
be stored under appropriate conditions to ensure
their suitability for use.
In-process Sampling and Controls
Written procedures should be established to
monitor the progress and control the performance
of processing
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PRODUCTION AND IN-PROCESS CONTROLS
Production Operations
Raw materials for intermediate and API
manufacturing should be weighed or measured under
appropriate conditions that do not affect their
suitability for use.
The processing status of major units of equipment
should be indicated either on the individual
units of equipment
Materials to be reprocessed or reworked should be
appropriately controlled to prevent unauthorized
use.
Time Limits
time limits should be met to ensure the quality
of intermediates and APIs
Intermediates held for further processing should
be stored under appropriate conditions to ensure
their suitability for use.
In-process Sampling and Controls
Written procedures should be established to
monitor the progress and control the performance
of processing
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PRODUCTION AND IN-PROCESS CONTROLS
Blending Batches
Blending is defined as the process of combining
materials within the same specification to
produce a homogeneous intermediate or API.
Blending processes should be adequately
controlled, tested for conformance and documented
The batch record of the blending process should
allow traceability back to the individual batches
that make up the blend.
Contamination Control
Residual materials can be carried over into
successive batches of the same intermediate or
API if there is adequate control.
Precautions to avoid and prevent contamination
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PACKAGING LABELING
General
Packaging and labelling materials should conform
to established specifications.
Records should be maintained for each shipment of
labels and packaging materials
Packaging Materials
Containers should be clean, provide adequate
protection against deterioration or contamination
If containers are re-used, they should be cleaned
in accordance with documented procedures
Label Issuance and Control
Access to the label storage areas should be
limited to authorised personnel.
Obsolete and out-dated labels should be destroyed.
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PACKAGING LABELING
Packaging and Labelling Operations
Labels used on containers of intermediates or
APIs should indicate the name or identifying
code, the batch number of the product, and
storage conditions, when such information is
critical to assure the quality of intermediate or
API.
For intermediates or APIs with a retest date, the
retest date should be indicated on the label
and/or Certificate of Analysis.
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STORAGE DISTRIBUTION
Warehousing Procedures
Facilities should be available for the storage of
all materials under appropriate conditions
separate storage areas should be assigned for
their temporary storage until the decision as to
their future use has been taken.
Distribution Procedures
APIs and intermediates should only be released
for distribution to third parties after they have
been released by the quality unit(s).
transported in a manner that does not adversely
affect their quality.
Special transport or storage conditions for an
API or intermediate should be stated on the label.
A system should be in place by which the
distribution can be readily determined to permit
its recall.
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LABORATORY CONTROLS
General Controls
adequate laboratory facilities.
documented procedures describing sampling,
testing, approval or rejection of materials
Any out-of-specification result obtained should
be investigated and documented according to a
procedure
primary reference standard Secondary reference
standards, reagents and standard solutions
Testing of Intermediates and APIs
An impurity profile describing the identified and
unidentified impurities present should normally
be established for each API.
Appropriate microbiological tests should be
conducted on each batch
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LABORATORY CONTROLS
Validation of Analytical Procedures
Certificates of Analysis
Authentic Certificates of Analysis should be
issued for each batch
The Certificate should list each test performed
in accordance with compendial or customer
requirements, including the acceptance limits,
and the numerical results obtained (if test
results are numerical).
Stability Monitoring of APIs
A documented, on-going testing program should be
designed to monitor the stability characteristics
of APIs,
Expiry and Retest Dating
API expiry or retest date should be based on an
evaluation of data derived from stability studies.
Reserve/Retention Samples
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VALIDATION
Validation Policy
The company's overall policy, intentions, and
approach to validation,
The critical parameters/attributes should
normally be identified during the development
stage or from historical data,
Validation Documentation
A written validation protocol should specify
critical process steps and acceptance criteria as
well as the type of validation to be conducted
A validation report cross-referencing the
validation protocol summarising the results
obtained, commenting on any deviations observed,
should be prepared
Qualification
Before starting process validation activities,
appropriate qualification of critical equipment
and ancillary systems should be completed. Design
Qualification (DQ), Installation Qualification
(IQ), Operational Qualification (OQ)
Performance Qualification (PQ)
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VALIDATION
Approaches to Process Validation
There are three approaches to validation.
Process Validation (PV), Prospective validation
Concurrent validation
retrospective validation
Process Validation Program
The number of process runs
Critical process parameters
Process validation should confirm that the
impurity profile for each API is within the
limits specified.
Periodic Review of Validated Systems
Systems and processes should be periodically
evaluated to verify that they are still operating
in a valid manner.
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VALIDATION
Cleaning Validation
In general, cleaning validation should be
directed to situations or process steps where
contamination or carryover of materials poses the
greatest risk to API quality.
Validation of cleaning procedures should reflect
actual equipment usage patterns
cleaning validation protocol
Sampling should include swabbing, rinsing, or
alternative methods
Validation of Analytical Methods
Analytical methods should be validated unless the
method employed is included in the relevant
pharmacopoeia or other recognised standard
reference.
Appropriate qualification of analytical equipment
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CHANGECONTROL
CHANGE CONTROL
change control system
Any proposals for GMP relevant changes should be
drafted, reviewed, and approved
Evaluate potential impact of the proposed change
on the quality
When implementing approved changes, measures
should be taken to ensure that all documents
affected by the changes are revised.
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REJECTION AND REUSE OF MATERIALS
REJECTION
Intermediates and APIs failing to meet
established specifications should be identified
as such and quarantined. The final disposition of
rejected materials should be recorded.
REPROCESSING
Introducing back into the process and
reprocessing by repeating a crystallization step
or other appropriate chemical or physical
manipulation steps is generally considered
acceptable.
REWORKING
Before a decision is taken to rework batches that
do not conform to established standards or
specifications, an investigation into the reason
for non-conformance should be performed.
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COMPLAINTS AND RECALLS
All quality related complaints, whether received
orally or in writing, should be recorded and
investigated according to a written procedure.
There should be a written procedure that defines
the circumstances under which a recall of an
intermediate or API should be considered.
The recall procedure should designate who should
be involved in evaluating the information, how a
recall should be initiated, who should be
informed about the recall, and how the recalled
material should be treated.
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RECOVERY RETURNS
Recovery of Materials and Solvents
Solvents can be recovered and reused in the same
processes or in different processes,
Fresh and recovered solvents and reagents can be
combined if adequate testing has shown
Solvents can be recovered and reused in the same
processes or in different processes,
Returns
Returned intermediates or APIs should be
identified as such and quarantined.
Records of returned intermediates or APIs should
be maintained.
If the conditions under which returned
intermediates or APIs have been stored casts
doubt on their quality, the returned
intermediates or APIs should be reprocessed,
reworked, or destroyed, as appropriate.
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Q A
Thank You