FDA'S NEW PROCESS VALIDATION GUIDANCE - THE INDUSTRY PERSPECTIVE
As the European industry has to comply with both US FDA and EU regulations, FDA's regulations are of great interest for the European industry just as much as for the industry in the US. Therefore the European Compliance Academy (ECA) decided to conduct a survey among its members to provide the FDA with information from abroad concerning the new Draft Guidance for Industry on Process Validation: General Principles and Practices; Availability.
By conducting a survey the ECA took a different approach than most of the other interest groups. The form of a survey was used to provide the FDA with feedback about the challenges this Guidance document poses in the context of the current validation requirements in Europe. The results discussed below were submitted to the FDA. The ECA comment as well as all the other comments can be found on the Internet at: www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2008-D- 0559.
In total 57 companies participated in the survey, among them 25 API manufacturers and 32 manufacturer of medicinal products.
The first question was related to "How companies implement the Life Cycle approach to validation?" There is still a need for more information because the answers showed very different strategies:
- Doing SPC/Statistics: 12 (API Manuf.: 5, FP Manuf.: 7)
- More focus on risk assessment: 8 (API Manuf.: 4, FP Manuf.: 4)
- More integration of development: 10 (API Manuf.: 5, FP Manuf.: 5)
- More Quality by Design activities: 5 (API Manuf.: 2, FP Manuf.: 3)
- Not new concept: 2 (API Manuf.: 2)
Some additional remarks: There are additional questions rising from the draft; asking for more clarification and some examples and suggestions to implement such new approach.
Also interesting is the fact that the majority of companies do not see a need to plan changes on their current validation concept at this point:
Recommendation
22/23 May 2024
Ongoing/Continued Process Verification - Live Online Training
Those companies that plan on changing their concepts mentioned to plan on introducing the following changes:
- Validation runs depending on complexity and understanding: 7 (API Manuf.: 5, FP Manuf.: 2)
- Continuous monitoring/Trending: 3 (FP Manuf.: 3)
Some additional remarks:
Widening and integrating process validation with PQR; use of incorporated online technology; ...regulatory assessment reports; one validation run possibility; possibility to increase validation runs up to 5.
We recognize a conflict of the new proposal and with the current regulation in Europe that requires a fixed number of validation runs. The survey showed that 15 manufacturers (API Manuf. 6 and FP Manuf. 9) will still prefer to do the established 3 runs (but with some comments indicated it "as minimum", as starting point").
The new requirement on continued process verification leaves a great variety of possible implementation procedures open. The feedback we received relative to the question how companies will react to the requirement of continued process verification is as follows:
- Via APR/PQR: 13 (API Manuf.: 7, FP Manuf.: 6)
- With Statistic/SPC: 6 (API Manuf.: 2, FP Manuf.: 4)
- Via Continuous improvement: 2 (API Manuf.: 1, FP Manuf.: 1)
In our understanding all these techniques seem to be in line with FDA's expectation.
The following figures may provide some information about already implemented measurements for process validation.
The questions were: Do you use process capability indexes (e.g. CpK values) in your company in order to demonstrate "process understanding"?
Do you use statistical process control (SPC) in your company in order to prove process safety?
Do you use Six Sigma in your company in order to increase process safety?
In the draft guidance the qualification steps are mentioned as more or less verification steps, therefore we asked "How will you react to the fact that the new FDA guidance does not mention DQ, IQ, OQ directly?"
The survey showed that most companies continue with DQ, IQ, OQ (PQ): 44 (API: 18, FP 26).
This is a great majority. Some comments we recorded were: we will continue to perform DQ, IQ, OQ as we need to comply also with EU markets; use GEP/QRM; new concept is not clear and we will continue with current practice, we prefer test cases with Specification, Design & Verification approach.
As a general feedback we recognize need for further harmonization in the field of GMP compliance, especially regarding the EU guidelines. In order to increase process understanding and patient safety, a harmonized and well understood guidance would be beneficial. Therefore we recommend also to discuss the new approach with EU regulators prior to finalization. A unified approach will avoid the use of hybrid systems for the industry which needs to comply with both EU and FDA regulations.
Some participants of the survey proposed to have more detailed information about practical aspects of implementation.
Recommendation
Tuesday, 28 May 2024 9 .00 - 16.15 h
Validation/Qualification for Beginners - Live Online Training
The procedures already established by industry show that different strategies exist to comply with the new requirements. However, we recognize some uncertainty about the correct strategy.
Author:
Daniel Scheidegger
... is Vice President Operations at Genzyme Pharmaceuticals' Liestal facility in Switzerland and chairman of the European Compliance Academy (ECA).
