In our News from 26 November 2008 we already informed you in detail about the FDA Draft Guidance on Process Validation published in November 2008. But where does the road lead? In order to lend you a hand here, we started a survey on FDA's new Process Validation Guidance in the News from 21 January 2009. The motto of the survey was "Which changes have to be made due to the new guidance?" In the following we present you the survey results. We would like to sincerely thank all those who took the time to fill in the questionnaire.
25 manufacturers of active pharmaceutical ingredients and 32 manufacturers of medicinal products, i.e. a total of 57 firms, took part in the survey (see ill. 1).
There was relative unanimity of the responses to the question: "How will you implement the Life Cycle Approach to validation?". 12 firms intend a stronger integration of SPC/statistics. 10 answers addressed a better integration of development activities, 8 firms place more emphasis on risk assessment. "More Quality-by-Design activities" was also mentioned expressly by 5 firms. So, with regard to the Life Cycle Approach, many companies seem to plan to focus on development in the future. But "no new concept" was also checked by 2 firms. Some of the comments revealed statements of uncertainty: "there are a lot of questions rising from the draft", "this guidance require more clarification and some e.g. such new approach", "no decision made yet".
Our next question was if you intended to change your validation concept in the future. Surprisingly, the majority of 35 firms replied "no". 22 firms answered yes (see ill. 2). Those firms that want to change something plan to do this by means of "validation runs depending on complexity and understanding" (7 answers), continuous monitoring/trending (3 firms). Further interesting individual opinions were: "widening and integrating process validation with PQR, one validation run, it´s up to the process". Details can be found in ill. 2.
"How will you handle the 'conflict' between the fixed number of validation runs required outside the US and the lack of such a number in the FDA-regulated environment ?", was another question we asked. 15 of the companies want to go on performing 3 validation runs, however, some commented: " as minimum", "as starting point". There were more very interesting comments: "There will be no conflict, only the performance of the process will have the final say", trend data and its analysis based justification with rationale, "trending output real time". But uncertainties became clear as well: "will follow current practices till things are not clear", "the fact is we need real concrete descriptions/examples of what FDA really means by this", "welcome but frankly still rather nebulous concepts".
Our next question concerned your reaction to FDA's call for "continued process verification". Here, with 13 occurrences the PQR/APR was the most frequent answer. Second came "with Statistics/SPC" (6 firms), and 2 firms intend to cover the requirement "via continuous improvement". On this topic, the FDA even won some praise: "We will thank FDA!", "this is a very good concept that can be easily implemented through process control", "the better control will help in maintaining the cost". Some companies already see their current procedures in compliance with the guidance: "in a sense we have always done this too", "we have a Q-System which review and control quality in a frequent way". But somebody also wrote: "not ready for this yet".
With the next three questions, we wanted to find out in how far you are using "modern" tools for process safety already today. For this reason we asked if you were using process capability indexes (e. g. Cpk values), SPC and Six Sigma. You can see the answers in illustrations 3, 4 and 5. What is surprising is that as many as 36 firms already use statistical process control (SPC) and 32 work with process capability indexes (see ill. 3, 4, 5).
The last question dealt with the fact that the new guidance does not include an explicit mention of DQ, IQ, OQ any longer. We wanted to know how you would react to that. Surprisingly 44 (!) firms intended to keep to their original concept. Some of the comments on this were: "but we will adapt a new concept frame", "to be on the safe side", "till concept is not clear, we will continue","but use GEP/QRM to reduce burden". Further comments were: "if it does not mention DQ, IQ, OQ the ressources can be moved to process improvement", "DQIOPQ to us was mainly for equipment, we are focused on performance of the process", "waiting if EMEA approves ASTM 2500, we have some test cases with SD &V (specification, design & verification) approach", "we (re)introduce the qualification steps and will continue to perform in this way", transition in which we will continue.
Conclusion: The majority of the participants in this survey have already thought about potential implementation possibilities. Above all, they focus on statistical statements/SPC; but APR/PQR as well as risk assessments are also likely to assume an important role. Here and there, uncertainties have surfaced, particularly in connection with the different specifications regarding the validation runs in the various regulations outside the USA and in the new guidance. The majority will probably continue to carry out the topic DQ, IQ, OQ in the customary form. Here, too, the differences between Annex 15 and the PIC/S document PI 006 with the FDA Guidance become clear. Therefore, ECA's Chairman, Daniel Scheidegger from Genzyme, has given this feedback to the FDA and asked the Agency to hold harmonisation talks with European supervisory authorities before the guidance will be finalised. You can view the comments on the draft guidance here.
A detailed presentation on the survey and the implementation possibilities of the new guidance is given within the framework of a validation session at the 3rd European GMP Conference in Heidelberg on 23-24 June. Take advantage of the ECA members' rebate of 30% until 31 March 2009.
On behalf of the European Compliance Academy (ECA)