1. The stability of a formulation product should be determined prior to marketing and also prior to adoption of any significant changes in the formulation or manufacturing procedures or packaging materials that may affect the shelf-life of the product
2. Stability study should be carried out a product in each package type in which it is proposed to be sold
3. At last three lots of the product should be made and evaluated for stability.
4. The sample size, test intervals and accelerated storage conditions should be based on statistical criteria for each quality attribute examined, in order to be sure of valid estimates of stability.
5. Where a product is to be reconstituted just before use, the stability of the product as well as that of the reconstituted product should be evaluated.
6. The quality attributes or parameters which should be checked in the stability study depend on the nature of the dosage form and its formulation. Each product has to be examined on its own merits. Broadly, the parameters under three headings:
Physical characteristics, purity and potency.
7. Physical characteristics may, among other things, include
| for tablets | : | odour, friability, disintegration, dissolution |
| Capsules | : | Condition of the shells, disintegration |
| Ointments & Cream | : | odour, texture, homogeneity, separation of ingredients, pH , etc. |
| Liquid | : | odour, taste, colour, viscosity, clarity, pH, non-homogeneity of suspensions, separation of ingredients, etc. |
| Injectables | : | Charity, particulate matter, pH separation of ingredients etc. |
Notes
The above mentioned are only illustrative. The exact quality parameters should be determined for every formulation.
1. Purity attributes may include moisture content for tablets and Capsules particulate matter and stability for Ophthalmic and parenteral preparations and decomposition products of the active ingredients in all formulations.
2. Potency should include the assay of all active ingredients and in the case of injectables and Ophthalmic formulations, effectiveness of bacteriostats preservatives.
3. stability of the package should also be studied.
Included in this are the appearance of the pack including the caps and other closures, the integrity of seals and adhesion of labels. Containers should be examined for corrosion, migration of container ingredients
(Particularly in the case of plastics) into the products and migration of the drug into plastic containers and gelatin capsule shells.
4. Methods of stability testing must be sufficiently specific to detect break down products and to distinguish between degraded and intact drugs, they should also be reliable and meaningful.
5. Where the formulation of the product includes more than one strength of the drug the stability data for one strength can not be extended to the other strengths unless the ratio of active to inactive ingredients as well as the nature of the inactive ingredients is the same.
6 Accelerated data should be considered as preliminary information only and should be supported by studies done at ambient temperatures.
7 The results of these tests should be recorded and compared with relevant original data for the batches & with similar repeat data on other batches. If these repeat results indicate that the expiry period may be too long and/or the recommended storage condition are unsuitable, reserve samples of different ages should be tested.
8. Where sufficient evidence has been gathered that the product does not keep as long as was anticipated from accelerated stability studies, the expiry period must be reduced and/or more stringent storage recommendations must be imposed
9. Changes of formulation, processes, raw materials and component materials, no matter how apparently trivial, must be evaluated for any possible effects on products on product stability.
10. Similarly, packaging material changes which may reduce the protection of the product from the environment need to be watched.
11. Minor changes such as change of raw material specifications or slight modifications of the process may not have adverse effects on stability and may be implemented.
12. Major changes such as product formulation changes, change of pack or drastic revision of material specifications are likely to have adverse effects on stability and should not be implemented before satisfactory full stability data has been obtained as described earlier
13. The results of such a study should be followed up with suitable action such as change in expiry period (if warranted) or/and change in associated storage conditions.
14. Batches of products produced after any major change must be clearly identifiable and should be closely watched for stability.
The following people have read this SOP and are currently following these procedures in the laboratory.
| Person | Signature | Date |