Transcript FPP specifications

Finished Pharmaceutical
Product Specifications
Rutendo Kuwana
Training workshop: Assessment of Interchangeable Multisource Medicines, Kenya, August 2009
Control of FPP
Four subsections
Specifications
Analytical procedures
Validation of analytical procedures
Batch analysis (against full set of specifications)
Full info on three or more batches e.g.
– Batch number and size
– Date/place of manufacture and QC testing
– Purpose of batches
– Batch number of API
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Specifications for the FPP
Specifications are one part of a total control strategy for
the FPP designed to ensure product quality and
consistency
Others include sound development studies and adherence
to GMP; e.g., suitable facilities, a validated manufacturing
process, in-process testing, stability testing, API testing,
etc.
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Biobatch vs Specifications
For the PQP, specifications should be designed to ensure
consistency with the biobatch. This then becomes the
starting and central point for dossier assessment
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Steps in setting specifications
 Identify critical product and process atributes
 Evaluate regulatory requirements
 Evaluate stability trends
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Critical Product Attributes
 Safety
 Physical
 Efficacy
 Chemical
 Quality
 Microbiological
 Biological
 Functionality
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Product Attributes – Example, Oral Suspension
 Presentation to the Patient
 Child resistant closure
 Tamper evident packaging
 Accurate dosing of correct medication
• Description (appearance, colour, odour)
• Identification (API, Preservatives)
• Dose delivery device (Physical characteristics of liquid –
viscocity, particle size)
• Uniformity of content, resuspendability, dissolution
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Specifications for the FPP
Should be as stated in the Pharmacopoeia; or
–
–
Release
End of shelf life
the concept applies only to products and establishes more
restrictive criteria for the release of the product
Compendial requirements – General chapters e.g. Dissolution,
residual solvents AND specific monographs
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FPP specifications (2)
Important reading for setting specifications:
 ICH guideline Q6A (also good for generics):Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances
and New Drug Products: Chemical Substances.
 ICH Q3B (R2): impurities in new drug products
 ICH Q3C (R3): Impurities – Guidelines for Residual Solvents
 ICH Q8 (2): Pharmaceutical development
 ICH Q10: Pharmaceutical quality system
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Specifications based on Compendial monographs
 Additional product related specifications, e.g.
– Those standard for the type of dosage form (e.g. friability, tablet
hardness, mass uniformity, viscosity)
– ID of colorants (skip testing?)
– microbial limits (skip testing?)
– ID and assay of preservatives
– Limits may be tighter than in monograph
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FPP specifications
Typical parameters (2)

Appearance

Identification of the following in FPP
 APIs
 Colorants (skip testing possible)
 Preservatives

Physical tests appropriate to dosage form e.g.
 LOD, friability, hardness (tabs)

Uniformity of dosage units (mass / content)

Pharmaceutical tests, e.g.
 dissolution
 Each API in FDC products
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FPP specifications
Typical parameters (3)

Purity tests
Degradation products (related substances)
Special attention to API-API degradation products
Residual solvents (solvents used in process)

Microbial count / sterility / bacterial endotoxins

Content of APIs in FPP (assay)
Limits 95.0% – 105.0%, unless justified

Content of preservatives
Limits 90.0% – 110.0%, generally acceptable
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FPP specifications
Example for uncoated tablets (1)
Attribute
Release limits
Stability limits
Appearance
Full description
Same as release
Identification
At least 1 method
Dimensions
Diameter, etc
Average mass
w.r.t. theoretical
Not required for
stability studies. Not
regarded as variables
for product.
Mass uniformity
Ph.Eur/USP/Int.Ph
Tablet hardness*
product specific
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Same as release
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FPP specifications
Example for uncoated tablets (2)
Attribute
Release limits
Stability limits
Friability*
≤ 1 % (normally)
Same as release
Dissolution
Set per product
Same as release
Disintegration
Not required if dissolution is done
Related substances
(degradants)
Only if formed during
production
Required. Limits to
one/2 decimal
Assay (content)
95.0-105.0%, unless
justified
May be 90.0-105.0,
if justified
Microbial limits
Skip-testing
end of shelf
* Tests not necessary at release if done in-process
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Analytical procedures
 Should be presented with sufficient detail to enable the
procedure to be repeated by another laboratory
 If a test is based on a Pharmacopieal monograph, a copy
of the monograph + any methods referenced in the
monograph must be submitted
 Details of any specifications and test methods additional
to those in the pharmacopoiea must be submitted
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General Requirements for justification of
specifications
 It is normally not necessary to test the FPP for synthesis impurities
that are controlled in the API and are not degradation products
 When a specification is first proposed, justification should be
presented for each procedure and each acceptance criterion
included. The justification should refer to relevant development
data, pharmacopoeial standards, test data for drug substances and
drug products used in toxicology and clinical studies, and results
from accelerated and long term stability studies, as appropriate
 Test results from stability and scale-up / validation batches, with
emphasis on the primary stability batches, should be considered in
setting and justifying specifications.
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Use of reference standards
 If a primary reference standard is available, then it should
be used
 When not available, then a reference standard should be
developed and qualified (See ICH Q6A) – information on
tests to establish identity, purity and assay value should
be provided
 Secondary working standards – content should be
assayed relative to the primary reference standard using
the same assay method
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