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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

Steps in setting specifications

Identify critical product and process atributes
Evaluate regulatory requirements
Evaluate stability trends

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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

Critical Product Attributes

Safety

Physical

Efficacy

Chemical

Quality

Microbiological
Biological
Functionality

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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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 Required. Limits to

production
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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

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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Assessment of Interchangeable Multisource Medicines, Kenya, August 2009