Medical device startups are mainly combining latest technologies (i.e., interconnectivity of medical devices, software and machine learning diagnosis with the help of Big Data). In doing so they demand highly skilled resources in each field of it. EUMEDIQ is often asked by startups for support in regulatory consulting during design & development stages. The experience shows that startups are often do not know the impact of a regulatory strategy to its project plans, shareholders & investors. While scoping the regulatory framework EUMEDIQ is often facing following challenges:
First of all, a prerequisite for a competent regulatory strategy is a well-defined intended purpose including clear defined medical claims/indications and contraindications supported by clinical investigation/evaluation (for IVD products: Performance study/evaluation), defined use scenarios and user groups. This is that much important, as every time it will change, the whole baseline for a sufficient regulatory strategy could get obsolete.
- Which are the markets to be entered with the medical device?
The type of product affects registration and submission of a technical dossier. As different markets have different submission pathways (i.e., combination products in US vs medical devices containing medicinal products in EU) and in addition the markets requiring different specific standards for presumption (EU) or attestation of conformity with its regulation.
Especially, after first successful market authorisation manufactures could face challenges which are avoidable with a solid regulatory planning. Aftern an initial EU market authorisation such challenges could be:
a) The chosen notified body is not part of Accredited Person program of FDA.
b) The accredited test laboratory has issued test reports according scope of harmonised standards but without global country-specific deviations and/or is not certified to ANSI/UL standards (i.e., electrical safety standards).
c) Conformity assessment according MDR Annex X and XI limiting flexibility of changes to the product after market authorisation.
d) Other countries might require ISO 13485 certification under Annex IX to market a CE device.
e) Canada require MDSAP certification.
f) Clinical evidence is not fitting the target user group in other countries.
g) Involvement and designation of economic operators like Importers and Authorised Representatives.
h) Business Plan schedule with inappropriate registration timelines.
There are a lot of things to be considered and it is emphasizing the importance of involvement of competent regulatory personnel in the earliest design & development stages. If not, considerable investments and resources (time & money) is required to “clean-up” the neglection of a solid regulatory strategy. Re-testing of country-specific deviations may require full test scope and accredited test laboratories have no short time capacities. Imagine investors and their expectations once a market authorisation was successful and startup manager need to tell them that the global supply requires additional notable investments and changes to the whole project/business plan.
2. Why written agreements are important for outsourced processes (i.e., contract manufacturing)
Often startups acting as so-called design developer companies by using the competence and resources of so-called contract manufacturers. Written agreements between the parties often lacking of know how regarding
a) Responsibilities, i.e., validation (master) plans & reports and product release.
b) Differences between contract manufacturer’s QMS and the QMS of the (legal) manufacturer.
c) Registration of establishments and roles as economic operators.
d) Notified body impact of the (legal) manufacturer to the contract manufacturer.
First, get everybody on the same page regarding the difference of a contract manufacturer and a (legal/regulatory) manufacturer. Responsibility can never be delegated. This means the product release is something the manufacturer needs to conduct on its own. Clearly defined product acceptance criteria, also required by ISO 13485 and 21 CFR 820, support the (legal) manufacturer in its goods incoming process to conduct a documented product release. Until then, the product needs to be quarantined at contract manufacturer premises and may never be shipped to 3rd parties which are not under control of the (legal) manufacturer.
Also, it should be noted that critical services like contract manufacturing requires the documented selection and evaluation of the supplier performance as required by ISO 13485. From the beginning the initial supplier performance could be demonstrated via supplier audit assessment. Therefor it is helpful to know the critical design parts, derived from Design Risk Analysis. In the audit assessment the capabilities of the respective contract manufacturer to these (critical) requirements & parts could be demonstrated properly and the decision is documented.
3. Feasibility projects: Aim to proof the design feasibility as a first step
Startups often dealing with challenging technologies & environments. Therefor, they often just focus to realize the product as a sample and demonstrate product conformity in order to ask for next investment approval. It should be clearly noted that in EU a proof of concept via type examination (MDR Annex X) approach in combination with product conformity verification (MDR Annex XI) might be the fastest way. But for type examination a representative product should be presented (as required for design validation by ISO 13485). Once successful, manufacturers often want to scale-up production and want to switch from handcrafted assembly processes to automated processes because the representative sample was not supported by statistical techniques. On top they need to think about substantial changes, depending on the competent authority the product was authorised, which are also limiting the flexibility and requiring massive time & resources. Prepared (drafted) regulatory strategy will show opportunities to investors after seeing first samples and let them balancing their risks and strategies.
In the end nothing is more normal than continuance of change but it can’t be neglected that startup managers should focus to be prepared with regulatory strategy questions in order to have valid answers for investors (board) regarding market access, timelines, opportunities and strategic partners.
Written by Mike Seidenberg, Senior Consultant
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