good manufacturing practice

I have short and basic question about  laboratory controls  ( We will be discussing the laboratory controls this week. Which area do you think it’d be most important to you?  Why?  And how does it compared with another industry (or area) that you are currently working with?

SUBPART I –
LABORATORY
CONTROLS
CHEM 519 – GMPs
1
Equipment
Standards/Materials
ANALYTICAL
LABS
Analysts/Training
Data system
Methods/Specs
2
1
SUBSECTION 211.160 GENERAL
REQUIREMENTS
• Establishment of or changes to required
specifications, standards, sampling plans, test
procedures or other lab control mechanisms
are drafted by the appropriate organizational
unit and approved by QA
• These are followed and documented at the
time of performance
• Deviations are recorded and justified.
3
SUBSECTION 211.160 GENERAL
REQUIREMENTS
Laboratory Controls will include the establishment of
scientifically sound and appropriate specifications,
standards, sampling plans and test procedures.
It must be assured that components, drug product
containers and closures, in-process samples, labeling and
drug product, conform to standards of identity, strength,
purity and quality.
Conformance to appropriate written specification must be
determined for components, drug product containers
and closures, labels, in-process materials and drug
product.
4
2
SUBSECTION 211.160 GENERAL
REQUIREMENTS
• Calibration of instruments, apparatus, gauges and
recording devices is done at suitable intervals
• According to a written program with specific:
• Directions
• Schedules
• Limits
• Remedial action
• Equipment and Instruments not meeting
established specifications, are not used.
5
SUBSECTION 211.165 TESTING
AND RELEASE FOR DISTRIBUTION
• Each batch of drug product is tested for
conformance to final specification
• These include identity and strength tests for
each active ingredient prior to release
• Testing for microorganisms is required, if the
product is required to free of them
6
3
SUBSECTION 211.165 TESTING
AND RELEASE FOR DISTRIBUTION

There are written procedures for sampling and testing

Acceptance criteria for sampling and testing are
adequate to assure the drug product meets specification
and statistical quality control for approval and release.

The accuracy, sensitivity and reproducibility of test
methods are established and documented

Drug product failing to meet specification or other quality
control parameters shall be rejected.
7
SUBSECTION 211.166 STABILITY
TESTING
• Written program to assess the stability
characteristics of a drug product.
• Testing is done using the product in the same
container system it is to be marketed in.
• Reliable, meaningful and specific test methods are
used.
• Written assessment of stability and compatibility
to indicate no degradation of the product for the
expected period of use.
ICH Organization
Q1A(R2) harmonized US, EU & JP
8
4
Q1A(R2) STABILITY TESTING
OF NEW DS AND DP
Establish requirements for necessary data to support an
expiration dating for a pharmaceutical products
• Storage conditions and frequency of testing
• Size and number of batches needed for registration
• Data for label storage condition and accelerated conditions
• Define forced degradation studies and stress studies
• Justification of specification
• Expectations of analytical procedures
• Requirements of labelling
9
Q1A(R2) – DS STRESS
TESTING
• Stress testing is required

To understand the drug substance stability

To establish degradation pathways

To validate the stability indicating power of the analytical procedures used.

To support the severe conditions that may be encountered during
distribution.
• Use single batch of material (high temp and humidity)

Oxidation, photolysis (ICH Q1B)
• Study depend on the individual API and DP.
• Degradation pathways can be complex and that, under forcing conditions, and
may not be realistic on long-term testing.
• Useful in developing and validating suitable analytical methods
• Results from these studies are part of regulatory submission
10
5
Q1A(R) DRUG SUBSTANCE

Testing:
• Cover attributes of the drug substance susceptible to change
during storage
• Cover, as appropriate, the physical, chemical, biological, and
microbiological attributes of the drug substance
• Validated stability-indicating test procedures should be
applied
• Acceptance criteria for the specific tests, set from preclinical
and clinical batches
• Should include individual and total upper limits for impurities
and degradation products
11
SUBSECTION 211.167 SPECIAL
TESTING REQUIREMENTS
• Drug products that are to be sterile or
pyrogen-free, appropriate lab testing will be
done.
12
6
SUBSECTION 211.170
RESERVE SAMPLES
• There are appropriately identified reserve samples
that are representative of each lot of drug substance.
• There are appropriately identified reserve samples of
each lot of drug product retained in its market
container and under labeled storage conditions.
• For drug product, the reserve sample is at least twice
the amount needed necessary to perform all required
tests except those for sterility and pyrogens
13
ANALYTICAL TESTING
CHEM 519 – GMPs
14
7
ANALYTICAL DATA
•Without Data, You Are
Just Another Person
with an Opinion
15
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Drug Substance (API) Release/Reassay/Stability
• Drug Product Release/Reassay/Stability
• In-process Samples
• Raw Material (Excipient) Release/Reassay
• Packaging Components Release
• Equipment Cleaning Samples
• Complaint Samples
16
16
8
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Method Transfer Samples
• Method Validation Testing
• Qualification of Standards
• Instrument Calibration
• Investigational Samples
17
17
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Drug Substance Release – Tests to Consider:
• Description/Appearance
• Assay versus a qualified reference standard
• Impurity Profile
• Identification Tests
• Residual Solvents, OVIs
• Water Determination
18
18
9
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Drug Substance Release – Tests to consider:
• Compendial tests, i.e., heavy metals, ROI, clarity
of solution, chloride, etc.
• Physical Tests, i.e., particle size, bulk and tap
density, surface area, polymorphic forms
• Microbiological tests particularly for APIs to be
used in parenteral formulations
• Chiral purity, specific rotation (as appropriate)
19
19
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Drug Product Release – Tests to consider:
• Description/Appearance
• Assay versus a qualified reference standard
• Degradation Product Profile (vs API impurity
profile)
• Identification Test(s)
• Dissolution or Drug Release
• Uniformity of Dosage Units
• pH
20
20
10
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Drug product release – Tests to Consider:
• Moisture Determination
• Clarity/Particulate Matter
• Preservative or Anti-oxidant
• Physical tests such as hardness or
disintegration
• Micro tests such as Bacterial Endotoxins or
sterility or antimicrobial preservative
effectiveness
21
21
SPECIFICATIONS
• Specification* is defined as (ICH Q6A):
• List of tests, references to analytical procedures
• Appropriate acceptance criteria that are numerical limits, ranges
or other criteria
• Establishes the set of criteria to which a drug substance or product
should conform to be considered acceptable for use
• Critical quality standards that are proposed and justified by the
manufacturer and approved by regulatory authorities as part of the
overall approval
*Substitute monograph or Quality Standard or Specs/Methods or
Specs/Tests depending on your company nomenclature
22
22
11
SPECIFICATIONS
• Specifications are part of total control strategy
designed to ensure drug substance/product quality
and consistency (also product safety)
• Characterization during development
• Adherence to GMPs
• Suitable facilities
• Validated manufacturing process
• Validated methods
• Raw material/in-house/stability testing
23
23
TYPES OF SPECIFICATIONS
• Release vs Shelf Life vs In-house vs Alert vs ???
• Concept of release vs shelf life applies to drug product only
• Establishment of more restrictive criteria at release vs shelf life
• In US, often criteria is the same from a regulatory filing standpoint
for release and shelf life which leads to establishment of in-house
or alert criteria
• In Europe, there is an expectation that a release and a shelf life
criteria will be filed for parameters that may change such as assay
or degradation products
• Regardless of how this is done the concept is the same, a tighter
limit is applied at product release to provide increased assurance
that the product will remain within acceptance criteria throughout
its shelf life
24
24
12
JUSTIFICATION OF
SPECIFICATIONS
• Development data
• Results for lots used in tox and clinical studies
(qualification of impurities)
• Results from accelerated and long-term stability
studies especially primary studies
• Reasonable analytical and manufacturing variability
• Data for scale-up/validation batches
• Exclusion of test (s)
25
25
• USP and typical industry limits are 98.0 –
102.0% on a dried or solvent free basis
• HPLC is most common method employed as
it can be shown to be specific and stability
indicating
DRUG
SUBSTANCE
ASSAY
• Titration is also used, however it must be
augmented by a specific method for
impurities
• Analysis for assay and impurities by HPLC is
often combined in one method, however it is
not absolutely necessary and often there are
two separate methods
• The drug substance HPLC method can be
the same as the drug product method,
however it is not absolutely necessary and
quite often the methods are different
26
26
13
DRUG PRODUCT ASSAY
• USP and typical industry limits are 90.0 – 110.0% of
label claim although some products have tighter limits
such as 95.0 – 105.0%
• In Europe, a release limit of 95.0 – 105.0 is an
expectation
• Many companies use in-house or alert limits set at
tighter than 90.0 – 110.0, these limits can be statistically
set based on the product degradation profile or more
arbitrarily set based on the variability in the method
and the manufacturing process
27
27
STABILITY TESTING
• Stability testing of degradation products
• Monitoring degradation products at levels > 0.1% or >
LOQ
• Isolation and identification of newly discovered
degradation products
• Reporting of degradation products
• Individual / total
• RRT / peak name
• Specified degradation products
• Response factor
• Authentic standard
• Area %
28
28
14
TESTING FOR IMPURITIES
• For new products, ICH guidelines Q3A and Q3B are in place
and include thresholds for Reporting, Identification and
Qualification of Impurities and Degradation Products
• Organic Impurities
• Identified /known impurities
• Specified impurities
• Unknown/unspecified impurities
• Total impurities
• Residual solvents
• Elemental Impurities
29
29
DISSOLUTION TESTING
• Dissolution Testing
• USP &
• USP Apparatus are Basket (1) and Paddle (2)
• Immediate Release Product
• Typical specification is Q = 80% at 15 –
60 minutes
• Extended Release Oral Product
• Typically 3 or 4 time points with Q
ranges, e.g.
• 1 hour 20 – 40 %
• 2 hour 40 – 60%
• 4 hour 65 – 85%
• 8 hour NLT 80%
30
30
15
ANALYTICAL TESTING IN
PHARMACEUTICAL LABORATORIES
• Typical Specification for:





Immediate Release Oral Tablet or Capsule
Extended Release Oral Tablet
Oral Liquid
Injectable solution
API
• Test
Method
Acceptance Criteria
• Assay
HPLC
90.0 – 110.0% of Label
31
31
FOR NEXT CLASS
For Next Class
Subpart J – Records and Reports
A. Reading Assignment: Chapter 10 – Laboratory controls
B. Discussion Board Assignment – Did you check?
C. Questions for me?
32
32
16

Don't use plagiarized sources. Get Your Custom Essay on
good manufacturing practice
Just from $13/Page
Order Essay
Calculate the price
Make an order in advance and get the best price
Pages (550 words)
$0.00
*Price with a welcome 15% discount applied.
Pro tip: If you want to save more money and pay the lowest price, you need to set a more extended deadline.
We know how difficult it is to be a student these days. That's why our prices are one of the most affordable on the market, and there are no hidden fees.

Instead, we offer bonuses, discounts, and free services to make your experience outstanding.
How it works
Receive a 100% original paper that will pass Turnitin from a top essay writing service
step 1
Upload your instructions
Fill out the order form and provide paper details. You can even attach screenshots or add additional instructions later. If something is not clear or missing, the writer will contact you for clarification.
Pro service tips
How to get the most out of your experience with Writall
One writer throughout the entire course
If you like the writer, you can hire them again. Just copy & paste their ID on the order form ("Preferred Writer's ID" field). This way, your vocabulary will be uniform, and the writer will be aware of your needs.
The same paper from different writers
You can order essay or any other work from two different writers to choose the best one or give another version to a friend. This can be done through the add-on "Same paper from another writer."
Copy of sources used by the writer
Our college essay writers work with ScienceDirect and other databases. They can send you articles or materials used in PDF or through screenshots. Just tick the "Copy of sources" field on the order form.
Testimonials
See why 20k+ students have chosen us as their sole writing assistance provider
Check out the latest reviews and opinions submitted by real customers worldwide and make an informed decision.
research analysis and writing
Great paper !!!
Customer 454525, January 26th, 2021
Health Care
I got an A. on this project thanks
Customer 453877, June 6th, 2020
Health Care
Excellent job
Customer 454677, March 9th, 2021
Accounting
Outstanding!!
Customer 454639, March 30th, 2021
Physics
AWESOME ASSINMENT
Customer 453877, March 7th, 2020
Economics
Excellent!! Great Work Exactly what I needed!!!!
Customer 455199, December 15th, 2021
Technology
Thank you
Customer 454677, April 27th, 2021
Senior Seminar
Great Job!!! Thank you
Customer 453503, April 21st, 2020
Psychology
I just finished reading this work good strong start and conclusion too. In addition follows APA guidelines. Thanks.
Customer 453877, April 18th, 2020
Sports
Great stuff
Customer 455371, June 26th, 2022
History
I got my essay 3 hours earlier, use this site instead of papersowl or edubirdie trust me I got scammed. This website is actually legit :) - Happy
Customer 455051, November 1st, 2021
Management
I got an A thanks.
Customer 453877, July 20th, 2020
11,595
Customer reviews in total
96%
Current satisfaction rate
3 pages
Average paper length
37%
Customers referred by a friend
OUR GIFT TO YOU
15% OFF your first order
Use a coupon FIRST15 and enjoy expert help with any task at the most affordable price.
Claim my 15% OFF Order in Chat
Live Chat+1(978) 822-0999EmailWhatsApp

Order your essay today and save 20% with the discount code GOLDEN