Working in the pharmaceutical industry, you can sometimes hear science and compliance talked about as if they are separate and unrelated. Two examples of what can be heard:
“Oh well, that is more of a compliance risk than a scientific concern.”
“You need to consider the compliance aspect of that change and then the scientific aspect.”
It should be stressed that good science is fundamental to cGMPs and interwoven in the regulations. For example, 21 CFR 211.160 states:
Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity.
The FDA Guidance Process Validation: General Principles and Practices states:
For purposes of this guidance, process validation is defined as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.
ICH Guideline Q9(R1) on Quality Risk Management states:
The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient.
Why is this issue being raised? This concept centers on risk; for example, what is the risk if a firm adopts the stance that good science is not fundamental to cGMPs and the regulations? Well, the danger is that good science is not incorporated into cGMP operations. Take the example of validation, where the focus results solely on execution of the validation and generating results to meet the established criteria, but if there is no scientific understanding of what the critical attributes/control strategy that are being validated are and how these factors impact the protocol results that are to be reported, it will not be a scientifically based strategy. There is also a risk that the protocol validation criteria are not scientifically based and, as such, there is no real basis for justifying the claim that, upon successful validation, the protocol is actually “fit for purpose.” Ultimately, there may be significant patient risk if a solid scientific understanding does not underpin validation activities. This is clearly recognized within cGMPs where, in the lifecycle management of process validation, stage 1 should be based upon establishing process knowledge and, from that, defining the control strategy.
A further example is change management. What is the risk of executing change management when there is no scientific understanding of the subject matter? Change management must be risk based, and a cornerstone of risk management (this is referenced throughout ICH Q9) is knowledge management/scientific understanding. A question that can naturally arise is, if it is recognized during the evaluation of a proposed change that there is a gap in an understanding – a gap in the scientific knowledge – what should a firm do? Well, firstly, one should recognize that such a gap in knowledge poses a significant risk in terms of accepting the proposed change with that gap and, as such, efforts should turn to acquiring that knowledge. However, as part of knowledge management, once you have remediated the gap, it is important to evaluate existing systems/processes/procedures that were potentially impacted by the knowledge gap, along with any proposed changes. This is an important aspect of knowledge management – one that can be at risk of being overlooked.
If you have questions related to knowledge management or any of the above topics, Lachman Consultants can help! Please contact us at LCS@lachmanconsultants.com for support.
