U.S. FDA Flags Five Procedural Lapses At Alembic Pharma's Jarod Facility

The U.S. drug regulator has flagged five procedural lapses at Alembic Pharmaceuticals Ltd.’s solid oral formulation manufacturing facility at Jarod, Vadodara, in Gujarat, during a pre-approval inspection.

"The U.S. Food and Drug Administration has conducted a PAI at Alembic Pharmaceuticals’ solid oral formulation facility (F-4) located at Jarod. The USFDA issued a Form 483 with five procedural observations," the company said in its Dec. 19 exchange filing. The inspection was conducted from Dec. 8 through Dec. 16 at the non-sterile drug manufacturing facility.

"None of the observations are related to data integrity, and management believes that they are addressable," the company said.

Form 483 is issued when investigators have observed any condition that, in their judgment, may constitute a violation of the Food, Drug, and Cosmetic Act and related acts.

"The company is preparing the response to the observations, which will be submitted to the U.S. FDA within the stipulated period," Alembic Pharmaceuticals had said in the filing.

BQ Prime has obtained a copy of the observation from the FDA.

1. Equipment and utensils are not cleaned or sanitised at appropriate intervals to prevent contamination that could impact the safety and quality of the drug. Four such instances were highlighted where written procedures for cleaning were inadequate or not followed, and corrective actions were not implemented in the case of sealing failures.

2. Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile were not established. Specifically, there was no written procedure detailing that laminar airflow, which involves fluid particles following smooth paths in layers, should not be obstructed while performing certain manipulations.

3. Failure to establish adequate written procedures for production and process controls designed to assure the quality and purity of drug products. Four separate instances were identified. Control parameters that could impact particle size were not clearly established, and there was no assurance that the packaging material used would deal with metal particulates generated during production. No procedures for visual inspection of a particular solution or in-process inspection of the integrity of materials used in certain processes were established.

4. Aseptic processing areas are deficient in systems for monitoring environmental conditions. Written procedures do not adequately identify where settle plates are placed during operations in reverse laminar air flow or laminar air flow—the sampling booth or barrier designed for providing the highest level of protection from airborne contaminants. Also, environmental monitoring records lack details regarding operations taking place during environmental monitoring under dynamic conditions such as personnel movement in and out of ISO 8 areas, which need certain levels of cleanliness.

5. Responsibilities and procedures applicable to the quality control unit are not fully followed. The written procedure on "deviation management" was not followed. While the firm experienced 133 deviations over a two-year period, only two deviation investigations were opened despite the criticality of the equipment.

The company has yet to respond to BQ Prime’s emailed queries on the implications of the observations, any impact on existing revenues, and the impact on the pending approvals and launch timelines. It’s also too early to comment on the steps being taken to address these issues and the expected timelines for resolution.

Shares of Alembic Pharmaceuticals were trading 0.21% lower as of 12:58 p.m., compared with a 0.36% decline in the S&P BSE Sensex.