GMP's as per US FDA Part I

This presentation is compiled by “ Drug Regulations”
a non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
11/29/2014 1

This presentation is compiled from freely
available resource like the website of FDA.
“Drug Regulations” is a non profit
organization which provides free online
Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
11/29/2014 2
Drug Regulations : Online
Resource for Latest Information

◦ This presentation is part I of series of presentations which addresses the current Good
Manufacturing Requirements as per the US FDA.
◦ Part A : Status , Scope & Definitions
◦ Part B : Organization & Personnel
◦ Part C: Buildings & Facilities
◦ Part D : Equipment
◦ Part E : Control of Components , Drug Product Containers & Closures
◦ Part F : Production & Process Controls
◦ Part G : Packaging & Labeling Control
◦ Part H : Holding & Distribution
◦ Part I : Laboratory Controls
◦ Part J : Records & Reports
◦ Part K : Returned & Salvaged Products
11/29/2014 3

211.160 ( a )
Appropriate organization unit should draft following and Quality Unit should review &
approve.
◦ Specifications
◦ Standards
◦ Sampling plans
◦ Test procedures
◦ Other laboratory control mechanisms
◦ Change in
Specifications
Standards
Sampling plans
Test Procedures
Other laboratory Control mechanisms
11/29/2014 4

211.160 ( a )
Follow and document at the time of performance.
Record & Justify any deviation from the written
specifications, standards, sampling plans, test
procedures, or other laboratory control
mechanisms.
11/29/2014 5

211.160 ( b )
Laboratory controls shall include the
establishment of scientifically sound and
appropriate
◦ Specifications
◦ Standards
◦ Sampling plans
◦ Test procedures
11/29/2014 6

211.160 ( b )
These should be designed to assure that following conform to
appropriate standards of identity, strength, quality, and purity.
◦ Components
◦ Drug product containers
◦ Closures
◦ In-process materials
◦ Labeling
◦ Drug products
11/29/2014 7

211.160 ( b ) ( 1)
Laboratory controls shall include:
◦ Determination of conformity to applicable written
specifications for the acceptance of each lot∗ within each
shipment.
∗ of components, drug product containers, closures, and
labeling used in the manufacture, processing, packing, or
holding of drug products
11/29/2014 8

211.160 ( b ) ( 1)
◦ Specifications including a description of the sampling
and testing procedures.
Samples shall be representative and adequately identified.
Procedures should include appropriate retesting of any
component, drug product container, or closure that is
subject to deterioration.
11/29/2014 9

211.160 ( b ) (2)
◦ Determination of conformance to written specifications
◦ A description of sampling and testing procedures for in-process
materials.
◦ Requirement of samples to be representative and
properly identified.
11/29/2014 10

211.160 ( b ) (3)
◦ Determination of conformance to written descriptions of
sampling procedures for drug products.
◦ Appropriate specifications for drug products.
◦ Requirement for samples to be representative and
properly identified.
11/29/2014 11

211.160 ( b ) (4)
Laboratory controls shall include the
calibration at suitable intervals of
◦ Instruments
◦ Apparatus
◦ Gauges, and recording devices
11/29/2014 12

211.160 ( b ) (4)
Controls shall include an established written program containing
◦ Specific directions
◦ Schedules
◦ Limits for accuracy and precision
◦ Provisions for remedial action in the event accuracy and/or precision limits
are not met.
◦ Requirement that instruments, apparatus, gauges, and recording devices
not meeting established specifications shall not be used.
11/29/2014 13

211.165 (a)
Determine for each batch of drug product
satisfactory conformance prior to realease to
◦ Final specifications
◦ Identity
◦ Strength of each active ingredient
11/29/2014 14

211.165 (a)
◦ Shortlived Radiopharmaceuticals
Release batches prior to completion of sterility and/or
pyrogen testing provided such testing is completed as
soon as possible.
11/29/2014 15

211.165 (b)
◦ Objectionable microorganisms
◦ Test each batch of drug product required to
demonstrate freedom from objectionable
microorganisms.
11/29/2014 16

211.165 (c)
Sampling and testing plans
◦ Describe in written procedures
◦ Include the method of sampling
◦ Include the number of units per batch to be tested;
Follow written procedures
11/29/2014 17

211.165 (d)
Acceptance criteria for the sampling and testing
◦ Adequate to assure that batches meet as a condition for
their approval and release
Appropriate specification
Appropriate statistical quality control criteria
◦ The statistical quality control criteria shall include
Appropriate acceptance levels
Appropriate rejection levels.
11/29/2014 18

211.165 (e)
Test Methods : Establish & Document
◦ Accuracy
◦ Sensitivity
◦ Specificity
◦ Reproducibility
◦ Follow §211.194(a)(2) for validation and documentation
11/29/2014 19

211.165 (f)
Rejection
Reject drug products failing to meet established
◦ Standards
◦ Specifications
◦ Any other relevant quality control criteria
11/29/2014 20

211.165 (f)
Reprocessing may be performed.
Prior to acceptance and use reprocessed material
must meet appropriate
◦ Standards
◦ Specifications
◦ Any other relevant criteria
11/29/2014 21

211.166 (a)
Stability Testing
◦ Written testing program
◦ Designed to assess the stability characteristics of drug
products.
◦ Use results in determining appropriate storage
conditions and expiration dates.
◦ Follow written program
11/29/2014 22

211.166 (a) ( 1)
Written program shall include :
◦ Sample size
◦ Test intervals
◦ Statistical criteria for each attribute examined
◦ Assurance of valid estimates of stability;
(2) Storage conditions
(3) Reliable, meaningful, and specific test methods;
11/29/2014 23

211.166 (a) (4)
Requirement of testing of the drug product in
the same container-closure system as that in
which the drug product is marketed;
11/29/2014 24

211.166 (a) (5)
Requirement of testing of drug products for
reconstitution
◦ At the time of dispensing (as directed in the
labeling)
◦ As well as after they are reconstituted
11/29/2014 25

211.166 ( b)
Expiration date
◦ Test adequate number of batches
◦ Determine an appropriate expiration date
◦ Maintain a record of such data
11/29/2014 26

211.166 ( b)
Tentative Expiration date
◦ Use Accelerated studies∗ for determination of tentative
expiration dates when full shelf life studies are not
available and are being conducted.
∗combined with basic stability information on the
components, drug products, and container-closure system,
may be used to support
11/29/2014 27

211.166 ( b)
Tentative Expiration Date
◦ Conduct Stability studies until tentative expiration date
is verified or
◦ Appropriate expiration date is determined
Where data from accelerated studies are used to project a
tentative expiration date that is beyond a date supported by
actual shelf life studies,
11/29/2014 28

211.166 ( c)
For homeopathic drug products, the
requirements are given in following slides :
11/29/2014 29

211.166 ( c) (1 )
Written assessment of stability based at least on
◦ Testing or examination of the drug product for
compatibility of the ingredients, and
◦ Based on marketing experience with the drug product to
indicate that there is no degradation of the product for
the normal or expected period of use.
11/29/2014 30

211.166 ( c) (2 )
Evaluation of stability shall be based on the
same container-closure system in which the
drug product is being marketed.
11/29/2014 31

211.166 ( d)
Allergenic extracts that are labeled “No U.S.
Standard of Potency” are exempt from the
requirements of this section.
11/29/2014 32

211.167 ( a)
Sterile and / or pyrogen free products
◦ Appropriate laboratory testing for each batch
◦ Determine conformance to above requirements
◦ Have test procedures in writing
◦ Follow test procedures
11/29/2014 33

211.167 (b)
Ophthalmic Ointment
◦ Determine conformance to specifications regarding the
presence of foreign particles and harsh or abrasive
substances.
◦ Follow all written procedures
11/29/2014 34

211.167 (c)
Controlled Release dosage forms
◦ Determine conformance to the specifications for the
rate of release of each active ingredient.
◦ Follow all written procedures
11/29/2014 35

211.170 ( a)
Retain Reserve Sample of Active Ingredient as follows
◦ Appropriately identified
◦ Representative of each lot
◦ Each shipment
◦ Each active ingredient shall be retained
◦ Sample at least twice the quantity necessary for all tests
Except for sterility and pyrogen testing.
◦ The retention time is as follows:
11/29/2014 36

211.170 ( a) ( 1 )
Reserve Sample
◦ The retention time is as follows for an active ingredient∗
in a drug product
◦ Retained for 1 year after the expiration date of the last
lot of the drug product containing the active ingredient.
∗ other than those described in paragraphs (a) (2) and (3) of
this section, the reserve sample
11/29/2014 37

211.170 ( a) (2 )
Reserve Sample
◦ For an active ingredient in a radioactive drug product, except for
nonradioactive reagent kits, the reserve sample shall be retained for:
◦ (i) Three months after the expiration date of the last lot of the drug
product containing the active ingredient if the expiration dating period of
the drug product is 30 days or less; or
◦ (ii) Six months after the expiration date of the last lot of the drug product
containing the active ingredient if the expiration dating period of the drug
product is more than 30 days.
11/29/2014 38

211.170 ( a) (3 )
Reserve Sample
◦ For an active ingredient in an OTC drug product that is
exempt from bearing an expiration date under
§211.137, the reserve sample shall be retained for 3
years after distribution of the last lot of the drug product
containing the active ingredient.
11/29/2014 39

211.170 ( b)
Drug Product Reserve Sample
◦ Appropriately identified
◦ Representative of each lot or batch of drug product
◦ Retained and stored under conditions consistent with
product labeling.
◦ Stored in the same immediate container-closure system
in which the drug product is marketed or
11/29/2014 40

211.170 ( b)
◦ In one that has essentially the same characteristics.
◦ Quantity shall consist of at least twice the quantity
necessary to perform all the required tests, except
those for sterility and pyrogens.
11/29/2014 41

211.170 ( b)
◦ Examined visually
◦ At least once a year
◦ Evaluate for evidence of deterioration unless visual examination
would affect the integrity of the reserve sample
◦ Representative sample lots or batches selected by acceptable
statistical procedures
Except for those for drug products described in paragraph (b)(2) of this
section,
11/29/2014 42

211.170 ( b)
◦ In case of sample deterioration investigate in accordance
with §211.192.
◦ Record the results of the examination
◦ Maintain with other stability data on the drug product
Reserve samples of compressed medical gases
need not be retained.
11/29/2014 43

211.170 ( b) (1)
◦ Drug products∗ shall be retained for 1 year after the
expiration date of the drug product.
∗For a drug product other than those described in
paragraphs (b) (2) and (3) of this section, the reserve sample
shall be
11/29/2014 44

211.170 ( b) (2)
◦ For a radioactive drug product, except for nonradioactive reagent kits, the
reserve sample shall be retained for:
◦ (i) Three months after the expiration date of the drug product if the
expiration dating period of the drug product is 30 days or less; or
◦ (ii) Six months after the expiration date of the drug product if the
expiration dating period of the drug product is more than 30 days.
11/29/2014 45

211.170 ( b) (3)
◦ For an OTC drug product that is exempt for bearing
an expiration date under §211.137, the reserve
sample must be retained for 3 years after the lot or
batch of drug product is distributed.
11/29/2014 46

211.173
◦ Animals used in testing components, in-process
materials, or drug products
◦ Shall be maintained and controlled in a manner that
assures their suitability for their intended use.
◦ They shall be identified, and adequate records shall
be maintained showing the history of their use.
11/29/2014 47

211.176
◦ If a reasonable possibility exists that a non-penicillin drug
product has been exposed to cross-contamination with penicillin,
the non-penicillin drug product shall be tested for the presence of
penicillin.
◦ Such drug product shall not be marketed if detectable levels are
found when tested according to procedures specified in
‘Procedures for Detecting and Measuring Penicillin Contamination
in Drugs,’ which is incorporated by reference.
11/29/2014 48

This presentation is compiled from freely
available resource like the website of FDA.
“Drug Regulations” is a non profit
organization which provides free online
Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
11/29/2014 49

GMP's as per US FDA Part I

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