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Problems with Deviations

Himalayan Institute, a dietary supplement manufacturer in NY, was issued a warning letter for violations of GMP regulations. The FDA noted in their investigations that several of the company’s batch production records showed deviations from the Master Manufacturing Record. For example, the company used ingredients other than the ones specified, but there was no documentation that they conducted a material review or made a disposition decision.

Dynamic Pharmaceutivcals, Inc. received a warning letter because their quality group did not conduct a material review and make a disposition decision for a manufacturing deviation where retesting was done. The quality group was not required by the firm’s procedures to investigate retested samples which failed their specification and the quality group did not make a disposition decision for this deviation.

A firm claimed to have established deviation procedures but provided no documentation. After an FDA inspection, a firm stated that they had implemented a deviation program, and training was given. When the investigator returned, there was no documentation showing that the firm had complied with its own procedures.

Why They are Important:

Detecting and managing deviations is important for many reasons. The intent is to make sure every batch of products made from the same master formula is uniform and meets the quality specifications. Since final product testing is not required for all dietary supplement products, meeting in-process controls and doing the manufacturing according to the written procedure is necessary to assure good quality of the final product. When deviations or unanticipated occurrences come up during manufacturing, they may be an indication that the product is not under control and, therefore, may not be able to be sold. The FDA requires quality personnel to conduct a material review and make a disposition decision if a batch deviates from the Master Manufacturing Record, including not completing steps or deviating from specifications. Deviations may also indicate that master manufacturing formulations may need to be updated based on variations in incoming raw materials or dietary ingredients.

When the QC unit is independent of manufacturing operations, it can provide an objective opinion about quality that assures the firm produces and distributes products free from defects. In situations where there is no quality unit to review, deviations or deviations are not reviewed, economic pressures can prevail, and decisions to release products to market may not be based on sound quality principles. The key is determining whether the deviations impact the product quality and determining if the batch should be rejected.

How to Improve:

First, set up a good OOS investigation plan program. An out-of-specification result is any value that does not meet the acceptance criteria of a specification. An OOS typically triggers an investigation plan. In the initial phase, the laboratory results are challenged by retesting the original and retained samples to compare results. If the original sample is still OOS, then an investigation of the manufacturing processes is started. Batch records, production processes, equipment status, and operation actions are all evaluated. At the end of the evaluation, Quality must make a disposition decision and decide whether the batch is OK or should be rejected.

Second, establish a CAPA program. Corrective and preventive action plans are needed to address the root cause of a deviation and to prevent a recurrence. CAPA plans have to be monitored to verify completion and effectiveness. A Corrective and Preventative Actions (CAPA) log is needed to record deviations. It should identify the specific deviation or the unanticipated occurrence, describe the investigation, evaluate whether or not the deviation resulted from or could lead to a failure, identify the actions taken to correct and prevent a recurrence, explain what was done with the component, dietary supplement, packaging, or label and explain a scientifically valid reason for any reprocessing work. The CAPA log allows trends to be identified and a record of the resolution of programs to be kept.

Then, determine Possible and Probable Corrective/Preventive Actions. Use various tools and techniques, such as brainstorming, cause and effect analysis, and statistical tools wherever possible or necessary. Involve people closest to the problem. Select the most effective or cost-effective corrective/preventive actions and then document your justification. When developing CAPA plans, you may need to redesign systems and processes. You should implement remedial training when needed and then ensure no further performance of the task until the necessary re-training is completed. You should set target dates and assign the individuals responsible for implementation. It’s important to use measurable outcomes so you can evaluate the effectiveness of the preventive actions.

Managing deviations and having an effective CAPA program can go a long way to reducing errors and problems in manufacturing. In addition to assuring you are sending high-quality products to the market, you will reap the benefits of reduced operating costs and increased productivity.

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