Cosmetic Manufacturers Pty Ltd.
4 extracted findings · 3 model-assigned issue types
FDA source excerpt, selected passage
You did not ensure drug products manufactured at your facility were evaluated for all critical quality attributes. You did not test (b)(4) drug products for identity and strength of the active ingredient (b)(4), and particulate and foreign matter. Additionally, you did not evaluate the preservative content of (b)(4)…
Findings and supporting evidence
Model-assisted readings, not an exhaustive interpretation. Compare with the extracted source findings below.
Drug products were released without appropriate laboratory determination of conformance to final specifications, including identity and strength of active ingredients and other critical quality attributes.
Supporting FDA text
Source excerpt · automated text-match checkYou did not ensure drug products manufactured at your facility were evaluated for all critical quality attributes. You did not test (b)(4) drug products for identity and strength of the active ingredient (b)(4), and particulate and foreign matter. Additionally, you did not evaluate the preservative content of (b)(4) drug product.
Laboratory controls were inadequate because specifications and test procedures for components and drug products were not scientifically sound, including inadequate testing of water and lack of suitability testing for bioburden methods.
Supporting FDA text
Source excerpt · automated text-match check(b)(4) is used in the formulation of your (b)(4) products and cleaning of production equipment. Your testing and specifications of your (b)(4) are inadequate. You did not test samples of (b)(4) for all significant quality attributes, including (b)(4). You also have not established suitability of test methods, including evaluating whether your drug product formulations intrinsically inhibit microbiological growth during bioburden testing.
Manufacturing process validation was inadequate for bulk solutions, with sampling lacking scientific justification and failure to meet pre-established acceptance criteria.
Supporting FDA text
Source excerpt · automated text-match checkYour manufacturing process validation was inadequate for (b)(4) bulk solutions. Your sampling methodologies lacked scientific justification, and you did not you test for the concentration of active ingredient (b)(4) in each product. Your manufacturing process validation for (b)(4) bulk solution relied on samples taken from the (b)(4) of a (b)(4) vessel that were analyzed for (b)(4) content. Your manufacturing process validation for (b)(4) bulk solution relied on samples taken from the (b)(4) of a (b)(4) vessel that were analyzed for appearance and (b)(4) content. The (b)(4) bulk solutions are (b)(4) and may be challenging to achieve uniform distribution of the ingredients due to their composition of approximately (b)(4)% (b)(4), respectively.
Environmental controls were inadequate for manufacturing areas, with action levels for passive air monitoring not appropriate for product exposure hazards.
Supporting FDA text
Source excerpt · automated text-match checkOur review of documents collected during the inspection also revealed you do not ensure (b)(4) drugs are manufactured in areas with adequate environmental controls. For example, your procedure governing environmental monitoring identifies your action level for passive air monitoring as (b)(4) colony forming units/plate following a (b)(4) exposure in manufacturing areas. If the product exposure poses substantial hazard (e.g., filling operation in which containers are (b)(4) or are exposed for more than a (b)(4) before closing), then the product should be filled in grade A with at least a grade C background. Otherwise, grade B or C air classifications may be appropriate for filling prior to terminal sterilization. Appropriate microbial levels should be established for these zones. In addition, the filling and closing operation should be adequately separated from the surrounding room environment, and it should be conducted under extensive HEPA filter coverage.
Equipment used in manufacturing was not adequately qualified for its intended use, and cleaning validation did not demonstrate reproducibility or worst-case conditions.
Supporting FDA text
Source excerpt · automated text-match checkYou have not demonstrated all equipment used to manufacture finished drug products is suitable for its intended use. You qualified the (b)(4) filler machine for the filling of (b)(4) in (b)(4) mL bottles following an inadequate product (b)(4) approach. For example, you filled (b)(4) mL of a (b)(4) product into (b)(4) bottles and (b)(4) mL of a (b)(4) product into (b)(4) bottles. The qualification documentation does not provide adequate scientific justification for this limited (b)(4) approach. It also does not explain how (b)(4) batch size products like (b)(4), which has a theoretical batch size of (b)(4) bottles, fits within the (b)(4) approach. The (b)(4) filler machine also failed to meet the qualification criterion for fill weight percent coefficient of variation for the (b)(4) product filled in (b)(4) mL bottles.
Cleaning validation was inadequate because it did not demonstrate reproducibility and did not justify using a different tank for validation.
Supporting FDA text
Source excerpt · automated text-match checkYou have also not established whether your cleaning procedures consistently reduce chemical and microbiological residues to acceptable levels. The cleaning validation protocol was not designed to demonstrate reproducibility of the cleaning process. For example, the cleaning validation protocol required (b)(4) swab samples to be taken from different locations for each of the (b)(4) qualification runs. Your cleaning validation also did not adequately justify the decision to use a (b)(4) tank in lieu of the (b)(4) tank used to manufacture the (b)(4) drug products. For example, there is no discussion of the (b)(4) tanks’ material(s) of construction and interior features (e.g., drains, ports, (b)(4)).
Findings extracted from the letter
Selected FDA passages, not the complete letter.
Source passage selected by the model
Source passage selected by the model
Source passage selected by the model
Source passage selected by the model
What FDA requested
Model-assisted summary. Consult the letter for complete requests and conditions.
- A comprehensive assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.
- An updated list of chemical and microbial specifications, including test methods, used to analyze each batch of your drug products before a batch disposition decision. Include: o A detailed description of how you will ensure drug products manufactured for distribution to the United States are held to suitable batch release criteria. Include any references to sources of information (e.g., specific qualified consultants and published materials including the United States Pharmacopeia). o Scientific justification for each chemical and microbial specification.
- An action plan and timelines for conducting full chemical and microbiological testing of reserve samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
- A summary of all results obtained from testing reserve samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
- A comprehensive assessment of all component and product specifications and limits associated with the manufacture of drugs for the U.S. market to identify and correct those that do not align with U.S. requirements.
- A procedure for your **(b)(4)** system monitoring that specifies routine microbial testing of **(b)(4)** to ensure its acceptability for use in each batch of drug products produced by your firm.
- The current action/alert limits for total counts and objectionable organisms used for your **(b)(4)** system.
- A procedure governing your program for ongoing control and monitoring that ensures the system consistently produces **(b)(4)** that meets **(b)(4)**, USP monograph specifications and appropriate microbial limits. The protocol, sampling method(s), and test method(s) used to assess potential growth inhibition of drug products you manufacture for distribution to the United States. The protocol and executed protocol report supporting the detectability of *Burkholderia cepacia* using your existing test method for detection of Pseudomonads.
Sections and clauses cited
As cited in this historical letter, not a statement of current regulatory requirements.