Warning Letter to US Company due to Lack of Product and Process Control

On 05 August, the FDA issued a warning letter to the US company LS Promotions Inc. in Hicksville. The warning letter is the result of a review of the company's responses to a 483 letter from the FDA. It summarises the violations of Current Good Manufacturing Practice (CGMP) for finished drug products under Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 21) found during the inspection as follows.

Laboratory Testing

Adequate laboratory testing was not performed on each batch of manufactured drug product prior to release to ensure compliance with specifications, including the identity and strength of the active ingredients. Similarly, microbiological testing was not carried out, although this is required for certain products, such as SPF 15 lip balm, SPF 30 sunscreen and hand sanitiser. The lack of testing means that it is not certain whether the products meet the specifications. The FDA therefore expects the company to provide a list of chemical and microbial tests, an action plan for conducting reserve sample analyses and a summary of the test results, including the measures to be taken in the event of substandard quality.

Stability

A suitable testing programme to assess the stability of the medicinal products to determine storage conditions and expiry dates was also missing. There was a lack of robust data to demonstrate that the chemical and microbiological properties remain acceptable throughout the shelf life. In the response to the 483 form after the inspection, there were also no details of any planned stability studies, particularly for products such as SPF 30 sunscreen and hand sanitisers. Without these studies, there is no scientific basis to ensure quality until the expiration date. Therefore, the FDA requires a comprehensive stability testing plan, including the definition of test methods and a continuous shelf life monitoring programme.

This was also seen in the particular aspect that LS Promotions further processed your supplier's SPF 15- lip balm bulk product by adding additional ingredients prior to bottling, but did not have data to demonstrate the stability of this altered formulation product in the finished containers throughout the shelf life.

Product and Process Control

Adequate written procedures for production and process control were not established to ensure the quality of the medicinal products manufactured. There was insufficient validation of manufacturing processes, including cleaning of production equipment. Again, LS Promotions' response was inadequate as neither a detailed validation programme nor a timetable for implementation was provided. A process validation programme covering the entire product life cycle and improvements to the cleaning validation programme are required to ensure that all manufactured products meet quality requirements.

Also in relation to the necessary cleaning and its validation for the filling lines used for multiple products was not in place, Here the FDA requires validation with worst case scenarios such as:

• Drugs with higher toxicity 
• Drugs with higher concentration of active ingredients
• Drugs with lower solubility in their cleaning solvents
• Drugs with properties that make them difficult to clean
• Swabbing sites for the most difficult to clean areas
• Maximum holding times before cleaning
• Poor change control management was also identified in this context.

Responsibility and authorisation of the quality units

In general, the FDA found that the Quality Unit (QU) did not fulfil its responsibility to ensure that the manufactured drug products comply with CGMP requirements. Adequate procedures to define the responsibilities of the QU, verify the identity of ingredients and ensure control over labelling were also lacking. No detailed plans for revising the QU procedures were submitted. Therefore, the FDA expected a comprehensive assessment and remediation plan to strengthen the QU, including review of procedures and oversight of production processes.

Further details can be found in the corresponding Warning Letter at the FDAs website.