FDA cited a facility for failing to adequately test in-process materials for quality after extended storage periods.
The firm established allowable bulk hold times for all tablet drug products without completing the necessary validation studies. This represents a violation of 21 CFR 211.110, which requires that in-process materials be tested and approved or rejected by the quality control unit.
Setting arbitrary hold times without scientific justification creates significant risk. Chemical degradation, physical changes, microbial growth, or moisture absorption could potentially occur during storage.
For hold times, FDA expects manufacturers to:
- Establish scientifically justified hold times based on actual stability data for each product and process stage.
- Design comprehensive studies that simulate real-world manufacturing scenarios, including worst-case conditions.
- Document and validate any retest or extension procedures with appropriate data.
- Apply hold times appropriately across all products or conduct product-specific studies where formulations differ significantly.
The highlighted 483 observation reads:
…..In-process materials are not tested for quality and approved or rejected by the quality control unit after storage for long periods.
Specifically, the allowable bulk hold time for all tablet drug products is … for the pre-compressed blend and… for the bulk tablets.
a. However, your firm has not completed bulk hold time studies for the … tablet drug products for thepre-compressed blend nor bulk tablets.
b. In the bulk hold time studies, your firm performed for the …. drug products, you did not include a study that assessed bulk pre-compressed blend study samples, compression of the bulk blend that was held for extended hold times, compression into finished tablets and then placement of these compressed finished tablets on stability.
c. Additionally, according to SOP …, “Scheduling Bulk Finished Product Retest”, your firm allows the extension of bulk finished tablets past the … bulk hold stage by retest. After retest, bulk tablets can be held for an additional … to a max … There is no data to support the bulk hold for all tablet products to ….
