Illumina Is Minding Its Ps and Qs for IVDR Compliance

Illumina seems to be crossing all its t's and dotting all its i's when it comes to compliance with the new IVDR regulations in Europe.

The company recently issued a press release announcing that it has obtained a CE mark under the new IVDR for the Illumina DNA Prep with Enrichment Dx. Yet, the company didn't seem all that concerned about pleasing the European Commission last year when Illumina acquired Grail during an ongoing investigation of the merger.

“Illumina is expanding its CE-marked IVD instrument and application offerings to help our customers achieve compliance with new regulations, underpinning our commitment to meeting the highest industry standards in improving the quality, safety, and reliability of IVDs,” said Paula Dowdy, senior vice president and general manager at Illumina for Europe, the Middle East, and Africa. “Illumina DNA Prep with Enrichment Dx offers clinical laboratories content flexibility and is fast and easy to implement.”

According to the company, the Illumina DNA Prep with Enrichment Dx marks the addition of a critical component in the transition of NGS workflows from inhouse assays built with research use only (RUO) components to in-house assays with IVDR-compliant components, with minimal workflow and service disruption. Compatible with existing CE-marked Illumina platforms, Illumina DNA Prep Dx with Enrichment Dx ensures scalability from low throughput to high throughput, the company said. It will also be compatible with Illumina’s future high-throughput IVD sequencing platform, planned to launch later this year.

IVDR, which came into effect on May, is enforceable by all EU member states for all IVD devices sold in Europe. CE-marking is mandatory for Class A (low personal risk, low public health risk) IVD devices, and IVDR certification from a notifying body is required for existing CE-IVD, Class C (high personal risk, mid-low public risk) products.

Illumina noted that it was one the first companies to apply for IVDR certification, presenting timely technical submissions for two Class C products. In November 2021, the company’s first IVDR certification was granted for VeriSeqTM NIPT Solution v2, a non-invasive prenatal test, and some existing IVDs, such as MiSeq Dx and NextSeq 550Dx have now moved to IVDR, with TruSight Cystic Fibrosis expected later this year.

The company also said its high-throughput diagnostic sequencing platform, which combines Illumina's top-of-the-range sequencer and genomics analysis server, is also on track for IVDR readiness.

After enduring much regulatory scrutiny, Illumina reported in August 2021 that it had gone ahead and acquired Grail, but that it would hold Grail as a seperate company during the European Commission's ongoing regulatory review. The European Commission wasn't happy with either company, considering the move a breach of the standstill obligation under the EU Merger Regulation. That led to a Statement of Objections informing Illumina of the interim measures the European Commission intended to adopt for the alleged breach.

“Illumina and Grail completed their merger, while our investigation is still ongoing,” Margrethe Vestager, executive vice president of the European Commission, said in September 2021. “Under our rules, companies have to wait for the Commission's clearance before implementing deals that are subject to our review. The standstill obligation is a cornerstone of our ex-ante merger control regime which aims at preventing harmful effects to competition while our review is ongoing. This is the first time companies openly implemented their deal while we are carrying out an in-depth investigation.”

Illumina argued that the European Commission didn't have jurisdiction to review the merger because Grail does not conduct business in the European Union. The company also said at the time that if it didn’t close the acquisition, it would be locked into a situation where the deal terms would expire before there was a chance for a full review.

"The decision to make the acquisition and hold the companies separate permits the regulatory processes to proceed while safeguarding the life-saving, pro-competitive benefits of this vertical transaction without the deal expiring,” said Charles Dadswell, general counsel at Illumina. "We will abide by any outcome ultimately reached by the courts.”

IVDR isn't as intimidating as previously feared

While the EU Commission's new Medical Device Regulation (MDR) has drawn considerable criticism from industry, complying with the EU IVDR might be less burdensome than previously thought.

RQM+, a regulatory, quality, and clinical consulting firm, published a white paper earlier this year spotlighting synergies between the IVDR requirements and the requirements of FDA in the United States.

“The EU Commission’s recent approved proposal means a sigh of relief for some IVD manufacturers with existing directive products on the market. It does not change the date of application, but allows for a progressive roll-out to the IVDR based on device classification, with a shorter timeframe for higher risk devices," said Carlos Galamba, vice president of IVD intelligence and innovation at RQM+, and author of the paper.

However, there is no room for complacency, he warns.

"Notified Bodies will not engage with companies unless their technical documentation, including performancedata is complete. I cannot stress enough how important it is for IVD manufacturers to review whether they have enough clinical evidence, to give themselves enough time to take remedial action," Galamba said. "We hope that this new paper will help manufacturers to plan efficiently for compliance, by making full use of what is already available.”

The RQM+ paper, "Performance Data and EU IVDR: Improving operational efficiencies through compliance," can be found here.