QUOTATION REQUIREMENTS

To assist ALS Pharmaceutical in providing an accurate quotation can you please provide the following information for your stability study by completing Table 1 on the following page:

1.  Temperature & Humidity conditions the samples will be held under, i.e. 2-8°C, 25°C/60%RH, 30°C/65%RH, 40°C/75%RH (RH = Relative Humidity)

2.  The time points when the samples are to be tested

3.  Tests required including the specifications. These are generally provided by the client from the product’s specification

Is any method validation required? If so then please also complete table 2 on page 3.

As a guide and to assist with the stability and method validation requirements, please see the information provided here.
STABILITY:
If the product specifications are not finalised or available then the following tests can be considered:
1.  Appearance: This description should be based on the Specification sheet for the product.
a.  Creams & Liquids (e.g. Dark blue non viscous liquid with a eucalyptus odour)
b.  Tablets (e.g. Round white biconvex tablet with a logo & breaker bar)
c.  Capsules (e.g. Soft Gel capsule with a clear fill content)
2.  Physical Testing
a.  Creams & Liquids (e.g. pH, Specific Gravity, Viscosity)
b.  Tablets (e.g. Diameter, Thickness, Hardness, Friability, Disintegration, Uniformity of Weight)
c.  Capsules (e.g. Disintegration, Uniformity of Weight or Fill Weight)
d.  Weight Loss / Gain
3.  Actives – method validation recommended
4.  Preservatives – method validation recommended
5.  Related Substances – method validation recommended
6.  Microbiological Tests (e.g. TGO77), Preservative Efficacy
METHOD VALIDATION:
1.  Where relevant it is a mandatory requirement that a method is validated when quantification of content is performed.
2.  When a validated customer method is supplied, Method Transfer Validation should be performed. Where Pharmacopeia methods are employed for assay, Method Verification should be performed.
3.  Where the client stipulates that validation is not required or when the method does not warrant validation, for example, in the testing of trial or R&D batches, the statement ‘The method/s have not been validated for this product’ will appear on the report.

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QUOTATION REQUIREMENTS

CLIENT NAME: SAMPLE NAME:

BATCH NUMBER: MANUFACTURE DATE:

PACK DETAILS (inc. Pack Size): EXPIRY:

TEMPERATURE: HUMIDITY:

Test / Specification / Time Point (Months)

Please supply multiple pages if more than one temperature/humidity condition is required.

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QUOTATION REQUIREMENTS

If Validation is required: To assist ALS Pharmaceutical in providing an accurate quotation, please complete the yellow sections of Table 2 with the following information:

1.  The analyte/s and the method validation level (please tick appropriate)

2.  If a custom method validation is required please tick all your desired parameters

3.  Placebo and methodology questions

Please see Table 3 on the next page for examples and recommendations.

Table 2: Method Validation Requirements

Validation Parameters / Full / Mandatory / Impurity / Custom
Linearity / Range / ü / ü / ü
Precision / Repeatability / ü / ü / ü
Intermediate Precision (Ruggedness) / ü / ü / ü
Reproducibility
System Suitability / ü / ü / ü
Accuracy / Level 1 / ü / at 10x LOQ
Level 2 / ü / If available
Specificity / Placebo / ü / If available / ü
Forced Degradation under 5 conditions:
1.  Heat
2.  Acid
3.  Base
4.  Oxidation
5.  UV light / ü
Not for ICP - OES/MS
ü
Impurities / ü
Limit of Detection / Quantitation
(LOD / LOQ) / ü
Robustness / Stability of solution / ü
Evaluation of method changes / ü
Analyte 1
Analyte 2
Analyte 3
Analyte 4
Placebo Available for Accuracy and Specificity? / Yes / No
ALS Pharmaceutical in-house method to be used?
Note: Customer supplied methods may incur a surcharge, please supply a copy / Yes / No

Table 3: Validation Examples - Based on ICH Q2 Guidelines (See www.ich.org for more details)

Validation Parameters / Detailed explanation / Full * / Mandatory / Impurity
Linearity / Range / 6 Standard levels across the working range of the method / ü / ü / ü
Precision / Repeatability / Analysis of 6 sample replicates by Analyst 1 / ü / ü / ü
Intermediate Precision (Ruggedness) / Analysis of 6 sample replicates by Analyst 2 / ü / ü / ü
Reproducibility / Inter-Laboratory testing, generally assessed during method transfer
System Suitability / 6 working standard injections assessing critical parameters (e.g. response, retention time) / ü / ü / ü
Accuracy / Level 1 / If no Placebo is available.
Triplicate spiking of sample at an additional 20% of the Label Claim / ü / at 10x LOQ
Level 2 / Preferred Accuracy procedure:
Triplicate spiking of placebo at 80, 100, 120% of the Label Claim / ü / If available
Specificity / Placebo / If available, the placebo is analysed for any interferences / ü / If available / ü
Forced Degradation under 5 conditions:
1.  Heat
2.  Acid
3.  Base
4.  Oxidation
5.  UV light / Standard only at 1 Level (High) / ü
Not for ICP - OES/MS
Standard only at 3 Levels (Low, Medium & High)
Standard & Sample at 3 Levels (Low, Medium & High) / ü
Impurities / If available, analysing known impurities for any interferences / ü
Limit of Detection / Quantitation
(LOD / LOQ) / Calculation of estimated LOD / LOQ from Linearity data / ü
Robustness / Stability of solution / Re-injection of solutions after x days to compare the response against freshly prepared standards / ü
Evaluation of method changes / Variations in critical parameters to assess the method’s robustness / ü

* These ‘Full’ validation parameters are recommended to comply with ICH guideline Q2 (Validation of Analytical Procedures: Text and Methodology). However if there are valid reasons for reducing the parameters assessed then the ‘mandatory’ parameters are acceptable. Examples being complementary medicines, preservatives, sunscreen actives, Elemental method validation via ICP-OES/MS.

Other Method Validation Related Activities – For example:

·  Method Transfer – The requirements for method transfer are generally client dependent and ideally should include a comparison of results between the transferring and receiving laboratory, e.g. Repeatability testing at both sites on three batches.

·  Method Verification – Generally employed for standard methods (e.g. Pharmacopoeial), including Linearity/Range, Repeatability and System Suitability.

·  Dissolution method validation – Generally only limited method validation is required, e.g. Linearity/Range, System Suitability and accuracy (Vessel spiking). This is however based on the fact that the analytical analysis method has previously been validated.

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