May 23, 2022

Warning Letter discussion-621313 -Part 2

3. Your firm failed to routinely calibrate, inspect, or check according to a written program designed to assure proper performance of and to maintain adequate written records of calibration checks and inspections of automatic, mechanical, electronic equipment, or other types of equipment, including computers, used in the manufacture, processing, packing, and holding of a drug product (21 CFR 211.68(a)).

The reasons of this observations are discussed below;

The firm did not calibrate or verify the accuracy of the temperature-controlled function of the equipment to ensure the manufacturing process is controlled for each batch.

The firm failed to calibrate or qualify the scale they used to weigh drug components.

4. Your firm failed to establish and follow written procedures for the preparation of master production and control records designed to assure uniformity from batch to batch. Your firm also failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.186(a) and 211.188).

The reasons of these observations are discussed below;

The firm did not prepare adequate master and batch production records for the drug product.

The batch records lacked:

• Approval signatures in conformance to a master batch record
• Detailed manufacturing instructions
• Identity of equipment used
• Sampling information
• Yield

The firm made several changes to the manufacturing process without justification or change control.

Without adequate batch records, one cannot assure the uniformity of the drug products from batch to batch.

5. Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions (21 CFR 211.25(a)).

The reasons of these observations are discussed below;

The firm failed to ensure that all personnel are qualified for the CGMP operations they perform.

For example, the co-owner stated that he is the sole proprietor of the formulation, had full knowledge of the process, and performed all manufacturing operations. However, there was a lack of evidence that the co-owner has the adequate experience to perform these functions nor has received the appropriate CGMP training.

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