Question

GMP Case Study Scenario
You are the quality control (QC) manager for a relatively new company that conducts manufacturing operations under contract to pharmaceutical companies. Your company’s facility handles rDNA protein products made in fermentation processes, followed by downstream purification steps, as well as and all testing. The facility was inspected in 2015 to local current good manufacturing practice (GMP) standards.  
The ongoing contract you have with SuperPharma P/L has entered a new phase. SuperPharma are providing a second generation production process, following on from the findings of their own R&D group. The product is SuperDrug-100, which is a small peptide made up of nine amino acids with no glycosylation (no carbohydrate substitutions). SuperPharma want the new process running in one month and your management has agreed to the timetable.
As QC manager, you are responsible for overseeing all steps performed by your staff to ensure that the tests associated with the changes in manufacturing SuperDrug-100 are introduced, performed and recorded appropriately in your lab. You were sent a memo stating that two completely new tests have been introduced: (1) an in-process test after the fermentation step (2) a purity test at release of the active ingredient – this is not a method you currently perform.   There are also two new components used in the fermentation medium.
You are also responsible for technical review of the SuperPharma R&D analytical findings, on which the modified process has been based. Some of their analytical assays show a slightly changed profile with regard to total impurities, and their assays are not validated in R&D. You are concerned that the quality of the material from the modified process might not be equivalent to the earlier batches. However, the product specifications have not been changed, and the new R&D materials are claimed to pass the original set of tests with the same limits as before, but the limits are very wide.

How could you eliminate concern that the very minor change in the impurity profile might be significant, since it appeared from the R&D reports that the scale-up work went very smoothly?

Answer 1

GMP simply means good manufacturing process. It is basically to ensure the quality and efficiency of end products. Generally quality assurence people make sures that standard GMP followed.

In above scenario first things should be done is to do R& D to find out nature and cause of purity. Since earlier batches were clean and scale up went smoothly, we can comfortably say manufacturing process is optimum and downstream processed product need further modification. The possible cause could be new added ingradients.

Following steps could be taken to ensure quality of product-

(1) Qualitative and quantitative analysis of impurity needs to be done to find out chemical nature.

(2) Toxicity and sensetivity profile of impurity need to be evaluated.

(3) If impurity is non toxic and safe for human than minimizing the content will be enough and complete elimination may not be required. It also need to be non interfering with action of new drug. In case the impurity is harmful, its complete elimination is necessary.

(4) Downstream processing need to be slightly modified to eliminate if possible, otherwise minimizing the amount of impurity.

(5) Standard GC-LC-MS methods are very efficient in tracking the purity of final product.

Once all the safety concern regarding impurity is dealt with and quality is ensured, product can be allowed to be manufacture.