Biopharma QC LIMS: Extinction or Evolution
For several years now, the future of Quality Control Labs and the Quality Control LIMS that automates and manages them has been a topic of debate. Some have predicted the imminent demise of both. Others have postulated that while QC Labs/LIMS will continue to exist, they will do so only by adapting. Adaptation here means by performing different functions than traditional “end-of-line” quality assurance testing.
Why all this speculation? Because the traditional function of QC Labs/LIMS in the biopharmaceutical industry is being pressured and affected by multiple forces and factors. We will explore some of these below and add our voice to the debate.
Quality by Design (QbD) & QC Labs/LIMS
The ‘Quality-by-Design’ (QbD) initiative came into being as a result of the suboptimal state of drug manufacturing around the year 2000. The cost of manufacturing drugs at that time was very high with waste being reported as high as 50%. Yet biopharmaceutical companies were doing little to improve their quality. There was a hesitation in the industry to implement new technologies because it was unknown how regulators would react to such innovations. The FDA addressed this in their Pharmaceutical cGMP for the 21st Century Initiative which placed the responsibility for product quality on the biopharmaceutical industry and by modernizing the regulations for manufacturing and product quality.
Successfully implementing QbD required that the biopharmaceutical company figure out how raw material attributes and the manufacturing process parameters affected the quality of the product. Estimating, guessing, or just plain old overkill manufacturing formulas and methods would no longer be accepted. In short, the FDA mandated that the biopharmas had to understand and then control their manufacturing by continually monitoring it. So knowing how to efficiently do raw material testing and in-process testing became paramount. This, in turn, affected what QC Labs/ LIMS would be doing. Or at least it seemed that way.
Raw Material Testing
Testing of incoming raw materials was a staple of the QC Lab. However, some biopharmaceutical manufacturers, as part of their QbD initiatives, started to require that their suppliers perform the quality assurance testing and deliver a Certificate of Analysis (COA) when they shipped their materials. By doing so, this standard function of the QC Lab and the QC LIMS was predicted to go away, but it really didn’t.
Many manufacturers were not comfortable with relying solely on the quality testing done by their suppliers. Instead they instituted Approved Supplier Programs. These programs certified suppliers and allowed most batches of raw materials to be accepted with just the supplier’s COA. Part of these programs was the development and institution of Skip Lot Testing. Skip Lot Testing is a set of algorithms that each biopharmaceutical company implemented to determine when full, in-house QA testing, partial QA testing, or just the supplier’s COA would be sufficient for each batch of raw materials. So while the amount of testing that the QC Lab performed was lessened, Skip Lot Testing algorithms grew very involved and complex. Therefore, automating them became necessary and the natural place to automate these algorithms was, of course, the QC LIMS.
The first aspect of QbD, therefore, did not eliminate the QC Lab/LIMS. Rather, it reduced the amount of testing in the lab but increased the amount of automation in the LIMS.
Process Analytical Technology (PAT)
Traditional quality control and assurance testing is performed by the QC Lab on both in-process and finished product samples. This type of sample management and testing is the bread and butter of the QC LIMS and was extensively automated in these systems. Specifications, Analyses, Testing Limits, and even Statistical Quality Analysis derived testing limits were all supported in the QC LIMS. However, with QbD, the desire to analyze in-process samples quickly, and then use the results to control and tweak the manufacturing process to increase quality, became paramount.
Process Analytical Technology (PAT) and its associated in-line and near-line instrumentation, therefore, began its rise in the biopharmaceutical industry; although it had been in use in the chemical/petrochemical industry for quite some time. This removed the need for in-process testing to be performed in the QC Lab, nor supported by the QC LIMS, again predicting the demise of QC Lab/LIMS. But it didn’t.
The QC Lab’s activities and testing of in-process samples was certainly reduced by PAT. However, not all the in-process testing could be performed by on-line or near-line instruments. Also, the QC LIMS continued to be the repository of the quality data as well as the mechanism for managing quality samples. This meant the utilization and function of the QC LIMS was not overly affected. Of course, if the biopharma company preferred to utilize an ERP like SAP to be the sample management and data repository, then the QC LIMS’ utilization was greatly diminished.
Other QC Lab/LIMS functions
While QbD and PAT have been very effective for reducing the costs and inefficiencies in the biopharmaceutical manufacturing process, there are still a great number of functions and complex testing that needs to be performed in a QC Lab/LIMS. A good example of this is Product Stability testing. The management of the stability samples, their locations, when and what needs to be tested, and the tests themselves is generally done in the QC Lab/LIMS. Another complex testing regime that is performed by the QC Lab/LIMS is Dissolution Testing. The complex algorithm for this type of testing is very well supported by a QC LIMS and the testing itself does not lend itself readily to an in-line style instrument.
QC Labs also perform other functions within a biopharmaceutical manufacturing facility. One such is the support of Environmental Health and Safety. There are regulatory requirements to be met in this space that necessitate the testing of the manufacturing environment on both a regularly scheduled and randomized basis. This is easily supported by a QC LIMS and the testing is generally performed in a QC Lab.
QC Lab/LIMS – Extinction or Evolution
It is clear that while QbD, PAT, ERP and MES have affected the role and testing performed in a QC Lab and its supporting QC LIMS, neither is in danger of going extinct any time soon. How and what the QC Lab/LIMS does and supports continues to evolve, and that is a good thing.
Has your quality assurance testing shifted to in-line testing methods? What functions and testing are being performed by your QC Lab? Has it changed over the years? Do you continue to use your QC LIMS or are you using other systems to support your needs?
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