1. Pharmaceutical Quality in the 21st Century
A Risk Based Approach
February 9, 2016
ASQ Member Meeting

2. How does FDA define Quality
When FDA is talking about Quality they are talking about cGMPs (current good manufacturing practices).
They are also talking about quality systems and viewing the manufacturing process as a whole.
This system view is what led FDA to their concept of Quality by Design.
The concept of QBD relies on the premise that the quality of a product must be designed into it and can’t be obtained by testing.

3. Why a Risk-Based Approach?
Much like ISO and other organizations are starting to realize, FDA has determined that in most cases, manufacturing firms know the critical steps that are required in order to product a quality product.
A quality system that focuses on the risk of things going wrong in the production process focuses on the critical steps in the process.
The FDA’s vision is also for more of the policies and standards used for the manufacturing process and for the regulation of pharmaceutical manufacturing to be more science-based.
FDA has started an on-going data analysis program that helps them identify risks and correlate them to inspection findings. They are starting to schedule inspections and allocate resources based on this data

4. Risk Based Strategies That FDA is Promoting
FDA promotes a proactive strategy to identify the risks in a manufacturing process.
Key areas where they want you to define the risks in a process are the:
Personnel
Facility Design
Environmental Controls
Timing and number of quality control tests
(Risk based approaches usually rely more on in-process testing that on final product testing.)

5. Science-Based Regulation of Quality
FDA is encouraging firms to find ways of mitigating risk through continuous improvement and innovation in the manufacturing process.
Focusing on pre-process and in-process testing to ensure the safety and quality of the products.
Looking at products using a life cycle approach where you continuously improve the manufacturing process using additional knowledge that is gained during the products life-cycle.

6. How will Risk-Based Approaches change the way FDA inspects firms?
The intensity of FDA oversight on product quality will be determined by several risked based factors with each product and firm:
The Degree of a manufacturer’s product and process understanding.
The robustness of the quality system controlling the manufacturing process.
Understanding which processes in the manufacturing of a product is critical to it’s safety.
Understanding which products serve a critical medical need or have a critical public health impact.
The compliance history of a firm will continue to be looked at from a risk standpoint.

7. How is FDA using Risk-Based thinking?
Starting in 2004, FDA started using the risk-based approach to prioritize domestic manufacturing site inspections.
They use the same approach in their review process of Investigational and New drug applications.
They have also begun to devote only highly trained “Pharmaceutical Inspectorate” staff to the inspection of prescription drug manufacturers and other complex or high-risk pharmaceutical operations.

8. Other FDA Practices changing:
FDA is also changing the documentation requirements for drug applications so that they are all reviewed the same way.
Chemistry, Manufacturing, and Controls are now submitted in an ICH format call CTD (common technical document).
This format allows for a more through review of the submission because the material is always provided in the same manner and may be divided into sections for further review if needed.
FDA is also working to harmonize their cGMP requirements with those of other countries so that global companies can better prepared for the submission of documents to FDA.