Stability protocols establishment

Formal Stability Studies — Long-term and accelerated (and intermediate) studies undertaken on primary or commitment batches according to a prescribed stability protocol to establish or confirm the retest period of a drug substance or the shelf life of a drug product. Impermeable Containers — Containers that provide a permanent barrier to the passage of gases or solvents (e.g., sealed aluminum tubes for semisolids, sealed glass ampoules for solutions). 

Product stability Inspection of the establishment to determine compliance with cGMP requirements and to conduct an audit of the data furnished to CDER in the application is a Field responsibility. This requirement applies to both the relevant preapproval batches, as discussed above, and the proposed commercial batches. CDER application review chemists are responsible for review of the proposed drug product stability protocol, specifications, and evaluation of the data submitted in support of the expira-... 

Preventative Action. This observation could have been avoided by establishing a stability testing program SOP that specifies batches that are to be entered into the annual stability program, including all container-closure systems, and that requires that all commercial container-closure systems be tested. The stability program must include an evaluation of degradants and impurities if it is intended to assess stability. Additionally, a product-specific stability protocol should have been developed that specified the methods to be used. 

Science drives decisions and shareholder value drives time lines. These issues generally have harmonious outcomes. Sometimes the time line becomes the main focus. This can cause stress and confusion and create artificial time constraints on a project. Sponsors can then transfer this new time line to the vendor. Vendors that hurry to meet a deadline and are subsequently asked to delay delivery of the final product (and thus wait to get paid) are unlikely to hurry and be as cooperative the next time. Sponsors need to know what is negotiable at the vendor site and what is not. An accelerated stability protocol that is scheduled to be under test conditions for 12 weeks simply cannot be completed in less time. If the sponsor is truly in need of an expedited event, it behooves the sponsor to have established a history of integrity with the vendor in order to enlist the vendor s full cooperation and understanding then the vendor knows it truly is a real deadline and will generally do anything within reason and regulation to help the sponsor. 

Coordination between sponsor and Agency chemists and pharmacoki-neticists to establish proper dissolution test procedures (particularly because dissolution testing will be included in the stability protocols,... 

After an application for a new drug product is approved, quality control tests must be established to demonstrate that the container closure system and all of its components possess the characteristics established in the original suitability studies. The appropriate packaging system should be included in all applicable stability protocols and observed for instability and drug product leachables. 

Stability report establishing expiry dating and Process validation protocol for formal three-batch validation of production-size batches. 

Products without an Approved Stability Protocol Applicants who have previously performed stability studies on a drug product without an approved protocol are required to submit an appropriate protocol under a Prior Approval Supplement under 21 CFR 314.70(b) or (g) or 601.12(b) (see Section V regarding an Approved Stability Protocol). On approval of the protocol, applicants may initiate stability studies on all annual batches under the ICH long-term conditions. Data from the first three consecutive annual batches after the switch can be used to verify the current—or establish a new—expiration dating period. However, if the applicant wishes to verify product stability under the ICH conditions over a shorter time span, three production batches within 1 year, instead of three consecutive annual batches, may be studied... 

A study protocol will be drafted by the appropriate organizational unit and must be reviewed and approved by the quality unit. Therefore, it would be time-saving if a company could establish a set of standard stability protocols. These standard protocols should include any specifications, standards, sampling plans, test procedures, and the time points needed for stability studies at different stages of development. 

Justification and prior approval would be necessary depending on the differences of the configuration studies in the stability protocol. QID establishes a series of possible scenarios where matrixing could be applied without prior approval. Options... 

The protocol established by the authors demanstrate that there is an increase of the activity retention of the immobilized lipase on the gelatine modified nanofiber membrane and on fhe chifosan-modified nanofiber membrane, compared to that on the nascent nanofiber membrane. The kinetic parameter Km values of the immobilized lipase on the nanofiber membranes are lower than that on the hollow fiber membrane. In comparison with the chitosan-modified membrane, there is a decrease of the Km value for the immobilized enzyme on the gelatine modified membrane. After immobilization, the pH, thermal and reuse stabilities of the immobilized... 

Specialized LIMS— This type of LIMS is based on the fact that certain laboratories have a range of well-defined processes (e.g., stability testing) that are performed according to a specific set of regulations and by using well-established tests. The tests are done according to industry-wide accepted protocols. Specialized LIMS are tailor-made for certain types of laboratories. Therefore the performance can be optimized for clearly defined work process. 

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