1. Finished Pharmaceutical Product Specifications
Rutendo Kuwana
Training workshop: Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

2. 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 2

3. 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. 3

4. 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

5. Steps in setting specifications
Identify critical product and process atributes
Evaluate regulatory requirements
Evaluate stability trends

6. Critical Product Attributes
Safety
Efficacy
Quality
Physical
Chemical
Microbiological
Biological
Functionality

7. 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

8. 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 8

9. Important reading for setting specifications:
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 9

10. 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

11. 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 11

12. 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 12

13. FPP specifications Example for uncoated tablets (1)
Attribute
Release limits
Stability limits
Appearance
Full description
Same as release
Identification
At least 1 method
Not required for stability studies. Not regarded as variables for product.
Dimensions
Diameter, etc
Average mass
w.r.t. theoretical
Mass uniformity
Ph.Eur/USP/Int.Ph
Tablet hardness*
product specific 13

14. FPP specifications Example for uncoated tablets (2)
Attribute
Release limits
Stability limits
Friability*
≤ 1 % (normally)
Same as release
Dissolution
Set per product
Disintegration
Not required if dissolution is done
Related substances (degradants)
Only if formed during production
Required. Limits to one/2 decimal
Assay (content)
%, unless justified
May be , if justified
Microbial limits
Skip-testing
end of shelf
* Tests not necessary at release if done in-process 14

15. 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

16. 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.

17. 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