YOUR SELEON SPECIALIST

Alexander Onghay
Senior Consultant Clinical Affairs

Tel.: 07131 2774-40
regulatoryaffairs(at)seleon.de

 

Questions on this topic?

Send us a message!

 

25.10.2021

AVOIDING NEEDLESS SIDESTEPPING

Since May 2021, good preparation and a lot of stamina are important magic words when it comes to implementing the requirements of the German MPDG for clinical investigations under the MDR. To avoid any unpleasant surprises, seleon informs you.

vorgaben-mpdg-zur-klinischen-pruefung
vorgaben-mpdg-zur-klinischen-pruefung
vorgaben-mpdg-zur-klinischen-pruefung
vorgaben-mpdg-zur-klinischen-pruefung

The German Medical Device Law Implementation Act (Medizinprodukterecht-Durchführungsgesetz - MPDG)has now formally entered into force on 26.05.2021 and has replaced the former Medical Device Law (Medizinproduktegesetz MPG) - at least for medical devices that are not in vitro diagnostics. But how will the innovations of the German stipulations affect practice? And what do manufacturers need to bear in mind to avoid unpleasant surprises?

The new law is a complex piece of work with direct reference to European legislation and a new overall structure. It is not only the merging of the content with other former regulations such as the Regulation on Clinical investigations of Medical Devices (MPKPV) that has increased the scope. The restructuring and the larger scope have already been discussed in earlier articles.

The medical device manufacturer, as the central addressee of the law, is confronted with a series of changes. He must assess the effects of these in detail for his company, his products, their further development and his comprehensive innovation policy. For some highly innovative start-ups, this can also become a fundamental question. To make matters worse, some effects will probably only become apparent in the concrete implementation details. A close look and good planning are therefore advisable.

All regulatory and legislative efforts at European and national level focus on the safety and performance of devices in clinical use. Appropriate clinical data for the medical device in question are required for proof. Unfortunately, the inclusion of data from "similar" products is becoming increasingly rare due to the narrower equivalence approach in the MDR. This means that own clinical data must be generated for the own medical device. In addition, clinical data must continue to be collected for the period after the device has been placed on the market.

Clinical data is the magic word. And that is why clinical investigations that deliver precisely this required clinical data as efficiently as possible will increasingly become the focus of manufacturers. We already reported on the handling of clinical investigations in the last article. The MDR requires clinical investigations for class III products almost without exception. But also for all other medical devices, it will often only be possible to generate suitable data in a study. Increasingly, manufacturers will also enter the ring again for product developments and then have to contend with the regulations that apply to products with CE marking when conducting studies. Overall, the focus is on patient-relevant data sets.

Manufacturers should therefore address the issue of clinical data and trials sooner rather than later - especially for existing products.

It is therefore not surprising that a significant part of the MDR and now also of the MPDG concerns the topic of "clinical investigations". We would like to try to shed some light on this and in one of the next blog posts we will focus on the changes of the MPDG with regard to clinical investigations. In doing so, we will highlight some aspects that we think need our attention, as they could have an impact on the type or duration of the procedure and thus cost the manufacturer valuable time until approval.

The changes that we would like to address concern, on the one hand, the area of classification of various clinical investigations (keyword "other clinical investigations") and, on the other hand, the area of approval procedures.
 

Let us first look at the application procedures for clinical investigations according to
MDR Art. 62:

The most obvious change in the application procedure for a clinical investigation is the newly introduced sequential processing by the responsible institutions: First, the application is processed by the ethics committee and then by the BfArM.

The MDR only regulates the requirements at the beginning of a clinical investigation:

  • MDR Art. 62 (4) a) Authorisation by national authority
  • MDR Art. 62 (4) b) positive vote of the ethics committee

An order is not specified and is also not required; parallel processing is possible. Member States are even explicitly free to decide which procedure to adopt (MDR Annex XV, Chapter II, point 4.2).

In the MPDG it is stipulated in § 38 (1) sentence 2 that the vote of the ethics committee shall be part of the application for the procedure at the BfArM - and thus the entire procedure is stretched forward.
 

How is this sequential procedure regulated in detail by the MPDG on the basis of
the MDR?

With regard to the application procedure and the processing of the application, the MDR provides a deadline of 10 days for the BfArM to check the competence and completeness of the submitted application (MDR Art. 70 [1] sentence 1). If documents have to be submitted, the manufacturer/sponsor is given a maximum of 10 days to provide them (according to MDR Art. 70 [3]). Thereafter, the BfArM has a further 5 days to again determine completeness. Since only one subsequent request is possible, this results in a maximum duration of 25 days until the start of the substantive examination of the application - if all regular deadlines are exhausted.

The MDR also provides for an extension of the deadline for the submission of documents from 10 to up to 30 days at national level. Furthermore, the MDR offers a further extension of all deadlines mentioned so far (MDR Art. 70 [4]) by up to 5 days each. The latter does not seem to us to be formulated precisely, because it would only make sense to refer to this 5-day extension for the examination deadlines of the BfArM, since the deadline for submission of subsequent documents has already been taken into account with the 20-day extension.

If the competence and completeness are determined by the BfArM, the applicant is notified - or not. According to MDR Art. 70 (5), the so-called validation date is set at the latest with the expiry of the above-mentioned deadlines, even if the BfArM does not react.

The deadline for the next phase of the authorisation process - the actual substantive examination of the application - begins with the above-mentioned validation. MDR Art. 70 (7) b) specifies 45 days for this period, which can be extended by 20 days at national level if external experts are still consulted by the BfArM. However, this only applies to certain higher risk classes. Clinical investigations for products of lower risk classes can already be started immediately after validation (MDR Art. 70 (7) a) (assuming a positive vote of the ethics committee). More on this later.

If the BfArM requires additional information from the applicant when reviewing the application, the 45-day period is suspended until the information is received (MDR Art. 70 [6]) - and without any limit on the number or other restrictions. Here, only practice can show whether this opening clause leads to non-calculable approval procedures.
 

How are the requirements of the MDR implemented in the MPDG in the Federal Republic of Germany, how are the design options provided by the MDR exploited?

Here already MPDG § 31 is surprising:

  • An additional 10-day "objection period" is introduced for clinical investigations that may already be started after the validation date (§31 (1) 1.). It remains unclear what will be examined by the BfArM during this period, which could then lead to an objection by the BfArM. This is because completeness has already been confirmed (=validation) and a substantive check is not provided for under MDR and under MPDG only for the correct application of the classification rule (MPDG §39 (3)). In the case of the latter, it can be discussed from our point of view whether this should not be checked beforehand. However, it is more problematic that it is currently not explained what happens after such a objection.
  • In addition, the division of the risk classes for which a substantive examination is to take place is amended: While the MDR only requires validation for class IIb (non-invasive), the MPDG requires a full approval process for clinical investigations on such devices.

In the MDR, which deliberately leaves this to the member states, there are no procedural instructions for the review of the application by the ethics committee. In the MPDG, this is extensively made up for.

As the sequential arrangement of the two application examinations has been established for the Federal Republic, the Ethics Committee (EC) must inevitably first examine the completeness and regularity of the application. The MPDG (§34 [1]) does not specify a time limit for this. It merely states that in the event of a subsequent request for documents, the applicant is granted a period of 10 days (§34 [2], first sentence).

Section 34(2), second sentence, unfortunately also states that the 10-day period for the Ethics Committee to notify completeness does not start until after the last document received, resulting in regularity. In practice, there will probably always be subsequent requests. With regard to the overall duration of the review by the Ethics Committee, this is another unknown.

A time limit for the actual review and consultation by the ethics committee is created by Section 36 of the MPDG in conjunction with Section 35 (3): The regular period until the vote is 30 days. This period is suspended if the applicant requests additional documents. An individually determined deadline is set for the applicant, which can, however, be a maximum of 45 days. A clear limit is set by the fact that the Ethics Committee can only request documents once. The consultation of experts by the EC also has a prolonging effect, but here we are talking about a maximum of 15 days.

Since the MPDG itself does not provide any further details on the time frame for the application procedure at the BfArM, it can be assumed that the above sequence according to the MDR - including a renewed check for completeness - will be implemented in practice by the BfArM.

As an interim summary, it remains to be stated from our point of view that the deadlines for processing by the ethics committee of 60 days and by the BfArM of 30 days, which were previously regulated in the MPG, have in part been shortened in the MPDG - but now with sequential processing. Although the processing times have changed, it is possible that the processing time will be considerably longer than before, in particular due to the almost unlimited possibility of requesting additional documents or information. It remains to be seen to what extent ethics committees in the preliminary review or the BfArM in the main review will make use of the current right to make several additional requests for information. It is to be hoped that important components and aspects of the application will, if possible, only be reviewed by one institution, which is indicated by Section 39 (1), and that therefore there may not be any excessive loss of time overall in the sequential execution. It is also to be hoped that not all deadlines will be exhausted.

The shift of products of risk class IIb (non-invasive) into the full application review will probably trigger discussions about the classification. Together with the possibility of objection by the BfArM in case of a different opinion regarding the risk classes chosen by the manufacturer with unclear legal consequences, resentment is pre-programmed.

A great deal of patience is required from the manufacturer of highly innovative medical devices anyway, since the complete technical file, including all test reports, must be available before the application for the test can be submitted, and the clinical investigation is still to be carried out after its approval. And this is followed by the processing time of the Notified Body of currently 6 to 12 months for certification. In this respect, it would (have been) desirable that no further stumbling blocks are placed in the way of a clinical investigation during the approval process. A conscientious examination of the content of all aspects required in the MDR is undoubtedly a sensible measure and leads to confidence among patients and users. But hurdles of a more formal nature should not be erected.


Does the new German law fulfil its intended purpose of implementing the EU regulations for clinical investigations at national level? Were clarifications and interpretations provided at the points required by the MDR that are prudent and conducive to innovation? Or have detailed regulations even created additional hurdles for medical device manufacturers and their products?

We definitely see some things in the practical implementation as critical. However, it remains to be seen how this will play out in actual approval life. After all, there is not yet much experience with the new regulations, not only among the medical device manufacturers, but also among the higher federal authority and then subsequently the notified bodies. It also remains to be seen whether innovations or changes will also occur in practice at the level of the ethics committees.

Here at seleon, we are concerned with even more aspects of the topic “clinical data”. We observe the new regulations in the daily field and what trends can be identified. You can therefore already look forward to our follow-up article on "Other Clinical investigations", which will then be dedicated to specific issues, so that you know what's going on.

 

Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.

Every product is unique – the mandatory tasks and measures for entering the market need to be specified individually. seleon advises you on your individual questions without any obligation.

CONTACT YOUR SELEON SPECIALIST

Further entries from the "Clinical Affairs" category

Clinical Affairs
25.10.2021

Since May 2021, good preparation and a lot of stamina are important magic words when it comes to implementing the requirements of the German MPDG for clinical investigations under the MDR. To avoid any unpleasant surprises, seleon informs you.

Clinical Affairs
07.07.2021

The manufacture of medical devices must comply with the latest scientific data and regulations, including the MDR. Clinical trials and evaluations form the basis for this. And on the far side, constantly adapted input brings about innovations, which in turn benefit the...

Clinical Affairs
13.04.2021

What are you actually facing during a clinical investigation of your medical devices? What do you need to know for the sake of your patients? Which standards and laws form the basis for this? seleon tells you!

Regulatory Affairs

Gaining approval for medical devices is complex and quite often also confusing. We bring clarity…

 

> Regulatory Affairs

Quality Management

Medical devices are governed by stringent requirements on quality assurance. We know the details …

 

> Quality Management

Development Excellence

Product development of medical devices is subject to its own rules. We bring light into the darkness …

 

> Development Excellence