FDA Sends Warning Letter to Merck and Company, Inc.
Please clarify the steps that your firm will take toward modernizing your specification/characterization procedures and practices. Currently, you have produced [redacted] lots of Asparaginase Intermediate Column Feed material (material prior to column purification). Please clarify how you will assure that these in-process lots of Asparaginase will meet their specifications for identity, strength, quality, and purity.
Furthermore, we note that in a recent correspondence during [redacted] from the Division of Therapeutic Proteins (HFD-122) within the Center for Drug Evaluation and Research to your firm regarding exemptions from the General Safety Test, the Agency communicated recommendations regarding expanding and modernizing the Asparaginase characterization tests. These recommendations include the use of Peptide Mapping, RPHPLC, SE-HPLC, SDS-PAGE (Coomassie and/or Silver staining), Western blotting using anti-E. Coli and [redacted]. Particulate analysis, and Bioburden as release tests to confirm the identity of Asparaginase. Other suggestions include carefully monitoring process-related (e.g. host cell proteins and adventitious microbial contaminants) and product-related (degradation products and aggregates) impurities. Mass spectroscopic molecular weight determination and analysis of free sulhydryls are also recommended to the firm.
Neither this letter nor the observations noted on the Form FDA 483 are intended to be an all-inclusive list of the deficiencies that may exist at your facility. It is your responsibility, as a drug intermediate manufacturer, to ensure that your operations are in full compliance with all applicable requirements of the federal regulations.
Please notify us in writing within 15 working days of receipt of this letter, of any steps you have taken or will take to correct the noted violations and to prevent their recurrence. If corrective actions cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed. Failure to promptly correct these deviations may result in further regulatory action, such as license suspension, license revocation, seizure and/or injunction, without further notice.
Your response should be sent to the Food and Drug Administration, ORA/OE/Division of Compliance Management and Operations, HFC-210, 5600 Fishers Lane, Rockville, MD, 20857.
If you have any questions regarding this letter, please contact Dr. Jacqueline Little, Team Leader, Team Biologics Compliance, Division of Compliance Management and Operations, at (240) 632-6854.
Sincerely,
David K. Elder
Director
Office of Enforcement
Votes:23
Comments: 0