原料药稳定性试验模板(国外)

Annex 3: Model Stability Report of Active Pharmaceutical Ingredient (API)

Prepared by: ...............................

Approved by: .............................

Date: ..........................................

Model Stability Report of ...................... Active Pharmaceutical Ingredient (API) Approved INN name

1. BATCHES TESTED

Batch

number

manufacture

Date

of

Site of manufacture

Batch size (kg)

Primary packing materials

Date of initial analysis

Note: the batches to be sampled should be representative of the manufacturing synthesis process and should be manufactured from different batches of key intermediates.

2. GENERAL INFORMATION

Structure

Chemical name(s)

Other non-proprietary name(s), e.g., national name, United States Adopted Name (USAN), Japanese Accepted Name (JAN); British Approved Name (BAN)

Chemical Abstracts Service (CAS) registry number

3. CONTAINER/CLOSURE SYSTEM

A description of the container/closure system(s) should be provided, including the identity of materials of construction of each primary packaging component, and their specifications. The specifications should include description and identification.

4.LITERATURE AND SUPPORTING DATA15

Before stability studies are initiated, information on the stability of the active pharmaceutical ingredient (API) should be sought, collected and analyzed. Published decomposition process and degradability of the API and the finished pharmaceutical products (FPP) should be referred to. Stability data can be presented on laboratory- and pilot-scale batches and on synthesis routes other than those proposed for marketing.

5. STABILITY-INDICATING

METHODS

ANALYTICAL

Make reference to the release specification number containing the description of validated, stability-indicating methods.

The accuracy as well as the precision (standard deviations) of the methods should be recorded. The tests for impurities and degradants should be validated to demonstrate that they are specific to the API being examined and are of adequate sensitivity

PLAN

6. TESTING

Storage time (months)

Storage condition

0 3 6 12 18 24 36 48 60 Accelerated: 40±2°C / 75±5 % RH X X X

%

RH X X X X X X X X X

65±5

30±2°C

/

Long term16:

Long term (2): 25±2°C / 60±5 % RH To be conducted only if the API is not stable at 30 o C

A significant change is considered to have occurred if:

the assay value shows a 5% decrease as compared with the initial assay value of a batch; any specified degradation product is present in amounts greater than its specification limit; the specifications for appearance and physical properties, e.g. color, are no longer met.

7. TEST PARAMETERS

7.1.Chemical characteristics [assay, contents of impurities and degradants].

7.2.Physical characteristics [e.g. appearance including possible change in color, moisture content as well as polymorphs if applicable].

7.3.Photostability testing should be conducted on at least one primary batch of the API.

7.4.Microbiological attributes (total microbial count and absence of pathogens, every year) when the API is intended to be used in a parenteral dosage form.

8. OTHER REQUIREMENTS

7.1. A stability report must be prepared giving details of the study results and conclusions. The results should be presented as both a table and a graph.

15 Literature data, if available, should be scrutinized, sometimes experimentally verified, and completed with information on polymorphism, particle size, hygroscopicity, etc., if applicable.

16 The long term studies should cover the whole retest period, which is not necessarily five (5) years.