Findings citing 21 CFR 211.67

Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)). You failed to adequately validate your cleaning procedures to ensure the removal of API residue and cleaning agents, as well as control of potential microbial contamination for your non-dedicated manufacturing equipment. In addition, you failed to adequately document the type of cleaning performed or the specific cleaning agent used to clean your equipment that is shared to manufacture both your OTC drug products and cosmetics. In your response, you acknowledge the weakness in your cleaning validation and cleaning documentation practices and commit to revalidating your cleaning process and updating your cleaning procedure. Your response is inadequate. You fail to provide sufficient details on the proposed cleaning revalidation and product impact assessment. In response to this letter, provide: Appropriate improvements to your cleaning validation program with special emphasis on incorporating conditions identified as worst case in your drug manufacturing operation. This should include, but not be limited to, identification and evaluation of all worst-case: o drugs with higher toxicities o drugs with higher drug potencies o drugs of lower solubility in their cleaning solvents o drugs with characteristics that make them difficult to clean o swabbing locations for areas that are most difficult to clean o maximum hold times before cleaning In addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product. A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment. A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices and encompass each piece of manufacturing equipment used to manufacture more than one product including both API and finished products. CGMP Consultant Recommended Based upon the nature of the violations we identified at your firm, we strongly recommend that your firm engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)). You failed to demonstrate that your cleaning practices are adequate to remove potential contaminants and to prevent drug product carry over in shared equipment used to manufacture your OTC drug products. For example, your cleaning validation program for the non-dedicated Unit (b)(4) Line (b)(4) relied exclusively on the visual inspection of…

Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated (21 CFR 211.22(a)). The records and information you provided demonstrate that…

Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment; and failed to perform operations within specifically defined areas of adequate size; and failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.67(b) and 21 CFR 211.42(c)). During our inspection, we observed inadequate cleaning and inadequate contamination control throughout your…

Your firm failed to establish an adequate quality unit and the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed (21 CFR 211.22(a) and (d). You lacked a quality unit (QU) with appropriate oversight for the manufacture of your drug products, and you did not have written quality procedures. Your firm has one SOP that does not adequately govern quality processes for CGMP. For example, you failed to ensure the following…

You failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).