Editor’s Note: This article was published in Pharmaceutical Technology Europe’s July 2021 print issue.
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Despite some improved understanding of adapted processes in light of the pandemic, information is still not filtered throughout the qualified persons community fully and more work by authorities and associations is required to improve communications.
In view of the COVID-19 pandemic and work-from-home guidance from public health bodies, the European Qualified Persons Association (EQPA), in March 2020, surveyed its members on the topic of “Remote QP Certification” (i.e., batch certification performed by a qualified person [QP] whilst not physically present at the site of the manufacturer). The topic was perceived as an area of non-harmonized national interpretations, and EQPA sought to better understand the differences across the European Union/European Economic Area (EU/EEA) and on how QPs positioned themselves in such a procedure.
One year later, in March 2021 with the pandemic still ongoing, it was expected that the situation in all organizations would have now settled with new modes of operation, including the QP certification procedure. EQPA decided that in the interests of all QPs it was time for a review on how this difficult period is being managed today. More than 300 QPs responded to a follow-up survey in which similar questions to the original survey were posed.
Editor’s Note: This article was published in Pharmaceutical Technology Europe’s July 2021 print issue.
The shift in the pattern of answers is, for the most part, quite modest although significant in some cases. It reinforces what was seen in March 2020 but with greater use of remote certification and more developed procedures generally. That may not necessarily be true with respect to the personal experience of each individual QP.
EQPA was interested in whether rules on remote certification might change in view of the pandemic and whether national legislative changes have been made that would continue beyond the pandemic period. As far as most QPs are aware, national rules on the topic, whether pre-existing or non-existent, have changed, but only for the duration of the pandemic. In March 2020, 50% of QPs across Europe believed that on-site certification was mandatory in their country. During the pandemic, this changed dramatically, and now 81% of QPs confirm that remote certification is allowed. This change is almost certainly because of the joint notice to stakeholders published, after the first survey, by the European Commission, the European Medicines Agency (EMA), and Heads of European Medicines Agencies in April 2020 indicating that all member states would accept remote certification in the light of the pandemic (1). This notice followed confirmation, in February 2020, by the Medicines and Healthcare products Regulatory Agency (MHRA) via its inspectorate blog that there was no legal obstacle to remote certification in United Kingdom (2). It appears, in the case of countries where on-site certification was previously mandatory, that this change to remote certification is temporary as no legislative changes are known to have been made.
The survey outcome becomes even more interesting if we sort the responses by country (Figure 1). A significant shift towards awareness of the acceptance of remote certification in most countries is apparent, reflecting the aforementioned official notice to stakeholders, but oddly, Italy and Romania show the opposite trend. Although the question, as posed, essentially required a “yes” or “no” answer as to whether the law allows or does not allow remote certification, the mix of answers from respondents from nearly each country demonstrates continued lack of clarity on this topic. After a whole year of the pandemic, neither QPs, nor the authorities, nor EQPA can provide clear and conclusive information to settle this question. Consequently, EQPA will continue to focus on this topic and will seek a harmonized regulatory approach across the whole of the EU/EAA.
It is surprising that despite the pandemic and official communications we do not see a uniform shift towards the right (awareness of the acceptance of remote certification) in the Figure 1.
The survey question actually offered three responses to choose from: not allowed, allowed but I do not use it, allowed and I use it. Table I shows this three-way split.
Across Europe in March 2020, nearly 20% of respondents did not believe that remote certification was accepted even in the midst of a pandemic. It is assumed that the difference in the more recent survey results can be attributed to the notice to stakeholders of March 2020. It is disappointing to note that the channels used by the health authorities and those of EQPA failed to reach all QPs effectively. In contrast, for example, the EQPA has seen a copy of a message understood to have been sent by the Irish Health Products Regulatory Authority (HPRA) to all QPs in Ireland, informing them of a relief from the obligation to perform certification on-site and the circumstances to be met to take advantage of this. Not surprisingly, as seen in Figure 1, such direct mailing was very effective, although still not 100%.
That said, QPs need to always be aware of national implementation or interpretation of European rules. EU directives are transposed to national law to fit with national circumstances and national authorities often add specific requirements resulting in some intra-EU variability. This is part of the EU system and works in practice, provided the objectives of the directives are met and that added national requirements do not interfere with the operation of the single market. For remote certification, we have the situation that an official communication by EMA and the heads of all of the national medicines agencies intending to waive national rules, at least for the duration of the pandemic, but national differences persist in practice. EQPA will continue to take a position against unnecessary national differences on this matter and call for a harmonized approach to remain after the pandemic is over. It has also been noted that differences can even exist within an individual member state so that one QP performing remote QP certification is supported by the authorities whereas another QP is not.
Despite the notice waiving any national requirements that restrict the ability to certify remotely, still 20% (2020: 23%) of QPs do not believe that, even in the midst of the COVID-19 pandemic, remote certification is a legally defensible option to pursue. From those who are aware that the option is possible, less than half of them used it in March 2021. In total, approximately 65% of QPs continue to perform certification on-site only.
Remote QP certification may need more regulatory specification given that it is not yet a properly defined concept. Whereas, it is clear that QPs can only be listed in EU manufacturing authorizations, giving clear territorial limitation to such activities, and importation testing can only be executed on EU soil, the definition of certification given in Annex 16 omits any similar territorial link or restriction. Let us imagine a scenario where a QP is employed in Germany but is domiciled in Switzerland. This is a possible scenario but not for QPs for pharmacovigilance (QPPVs) according to directive 2001/83/EC (3). In view of the pandemic, if the aforementioned QP decides to work from home, is it now legally acceptable to certify remotely from a third country? The Mutual Recognition Agreement (MRA) with Switzerland, like all similar MRAs, is built on the concept that QPs cannot be established in Switzerland. For certification to be accepted by the EU, it has to take place within the EU. A potential conflict now emerges.
One of the survey questions explored which arrangements were seen as most important by QPs for establishing and maintaining remote certification. Some shifts can be seen in the most recent answers compared to the first survey. More importance is given to having clarity on the location where certification takes place (63% → 74%) and assurance that a complete set of documents and data is available (84% → 91%). Reduced interest is noted on clarification of the location of the batch register (76% → 56%) and oversight of the quality system (78% → 71%). This may nevertheless be more indicative of the greater challenges posed here by the pandemic rather than a conscious shift in bias. Twenty percent of respondents in 2021 (30% in 2020) are satisfied with limited data and documentation to support remote certification during the pandemic. This poses a critical question as to why a certification procedure conducted remotely would need to be supported by different batch data and documentation compared to on-site certification.
One issue that needs to be resolved when using remote certification is the appropriate exchange of data, documents, and certificates. In good manufacturing practice (GMP) environments, this can occur either by paper or validated IT systems. Email should not be considered robust or compliant, and it may not be amenable to validation according to Annex 11. Up to 80% of QPs in the follow-up survey are able to rely on direct access to IT systems, exchange platforms, paper exchange, or hybrid systems. This is a slight increase of 5% compared to March 2020. Still, between 16 and 20% of existing procedures rely mainly, or fully, on emails. Those procedures should be highlighted for urgent change if they have not already been identified as a GMP deviation. Exchange platforms supporting remote interaction are available that provide safe data, documentation, and certification exchange.
A series of the survey questions explored how remote certification was introduced in terms of the Pharmaceutical Quality System (PQS). Roughly one third of the responses indicate that a deviation was opened, half of the responses confirm a change request and 75% finally adopted procedures within their PQS to better describe the remote certification procedure.
Annex 16 and other references require many tasks to be completed prior to certification of a batch. One of the survey questions explored a potential list of data, evidence, and documents that the QP should have to hand to support remote certification (Figure 2). From March 2020 to March 2021, QPs significantly improved their access to relevant data, evidence, and documents to bolster their remote certification procedures, which is an encouraging development. While in March 2020, for example, process validation summaries were only available to 50% of QPs. A year later, these summaries are available to 58% of QPs. Despite this improvement, validation summaries stay the weakest area of the offered list of data elements; whereas, the range of confirmed availability is now between 58–100% (2020: 50–96%). Note that the potential list of data elements used in this survey question for respondents to select from was taken from the MHRA Inspectorate blog published in February 2020 in which MHRA expected all to be available to QPs (2).
The importance and meaning of the batch register remains a continued area of discussion within the QP community. Its importance seems to have diminished considerably judging by the shift in the answers between the two surveys. While in March 2020 at least 76% of respondents agreed that it was important to clarify the location and control of the batch register in the context of remote certification, in March 2021 this was considered important for only 54% of QPs. This seems to indicate that the register is disregarded by many QPs, whether for good and bad reasons. The authors nevertheless continue to point to the definition of QP certification according to Annex 16. According to this, certification cannot be completed or executed without a register or equivalent; although notably, it can be completed without the issuance of a batch certificate. Either the requirement needs to be clarified to better understand the purpose of the register, or it may even be eliminated. Better training of QPs on this aspect may be needed.
Repeating the survey for a second time was intended to show progress in arrangements around Remote QP Certification and how QPs coped throughout the pandemic. While many QPs made obvious progress to stabilize their certification processes in light of the pandemic, some gaps remain and should be closed. Data exchange could still be improved for many, and some gaps and hurdles remain in relation to access to a regular set of data to support remote certification. While gaps may be found in execution of remote certification, shortcomings also exist in harmonized rules for its execution as well as on related matters, such as the role and use of the batch register and data elements needed to support certification. Although health authorities and associations like EQPA made information and new aligned positions publicly available, there is still room for more efficient and effective communication in a rapidly changing scenario. One of EQPA’s aims is to ensure that QPs do not miss new applicable guidance, or its interpretation, on topics crucial to continued operations. It is not acceptable that QPs should be unaware of public guidance one year after its publication.
1. EC, “Notice to Stakeholders: Questions and Answers on Regulatory Expectations for Medicinal Products for Human Use During the COVID-19 Pandemic,” ec.europa.eu, Section 2.5, Brussels, 10 April 2020 (Revision 3—1 July 2020).
2. T. Watson, “Maintaining Control: Remote Working and QP Certification,” MHRA Inspectorate Blog, 25 Feb. 2020.
3. EC, Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code Relating to Medicinal Products for Human Use (16 Nov. 2012).
Dr. Ulrich Kissel is chair of board of the European QP Association; with editorial input from David Cockburn, board member of the European QP Association.
Pharmaceutical Technology Europe
Vol. 33, No. 7
Pages: 36–38, 41
When referring to this article, please cite it as U. Kissel and D. Cockburn, “Survey of QPs on Remote Certification” Pharmaceutical Technology Europe 33 (7) 2021.