Top stories: ICH welcomes new members and previews upcoming guidelines. European Commission starts consultation on supply chain changes and legislation. India looks to speed access to vaccines with foreign data. MHRA offers a pathway for 3D printed devices for COVID-19. Remdesivir’s global debut underway.
By Alexander Gaffney, MS, RAC and Charles Friend
Welcome to AgencyIQ’s International Brief. We know that international regulatory agencies can have a profound impact on both global life sciences companies and the FDA, and we want to make sure we’re regularly highlighting some of the biggest actions taking place outside of the US. We intend to publish every Thursday to start, and potentially more frequent coverage soon after. We’re thinking of this as a work in progress, so please send along your thoughts, wishes and tips to firstname.lastname@example.org.
1) ICH expands, with new guidelines on the way
By Alexander Gaffney, MS, RAC
The International Council for Hamonisation (ICH) this week announced that its membership has grown by one official regulator and one observer, and that it is moving ahead on a new guidelines.
- New additions to the ICH include the Turkish Drug and Medical Device Institution (TITCK) and Lebanon’s Ministry of Public Health (MOPH). TITCK is being added as a full regulatory member, while Lebanon’s MOPH is being added as a regulatory observer.
- ICH also noted that it has two guidelines that have reached Step 4 in the development process in the last two months: A Q&A document intended to supplement its M8 guideline on eCTD submissions under the v4.0 standard, and a new S11 guideline on nonclinical safety testing in support of development of pediatric medicine. The EMA has already released the S11 document and plans to adopt it in September 2020. The FDA has not yet released any update to its 2019 draft guidance based on the guideline.
- The next guidelines to be worked on include a new guideline on structured product quality submissions, as well as a revision to the M4Q(R1) document on the Common Technical Document. ICH’s leadership also supported development work on its E4 guideline on dose response information to support drug registration, and a separate guideline on considerations for model-informed drug development.
- New dictionary terms to support COVID-19. The ICH is also in charge of a regulatory dictionary called MedDRA, which is used to standardize the way in which medical information is conveyed by companies. The MedDRA has been updated to include approximately 70 new terms related to COVID-19, the ICH said.
2) European Commission looks into drug supply chain issues and legislative reforms
By Alexander Gaffney, MS, RAC
The US isn’t the only country where legislators are furiously looking into reforms that could help countries be ready for the next public health crisis following COVID-19. The European Commission now says it’s launched an initiative to “address all levels of the value chain,” as well as lessons learned from the current outbreak.
- The roadmap is the result of concern about drug shortages, affordability and access, the commission wrote in an accompanying document. COVID-19 has “demonstrate the serious exposure of … the EU health and pharmaceutical sectors,” it explained. “The EU’s growing depending on imports of medicines and active pharmaceutical ingredients due to manufacturing outside the EU may result in shortages in case it is not counterbalanced by a sufficient level of diversification of EU supply chains.”
- The argument is similar to ones happening around the world, including in the US, where legislators have called for study of the US’ reliance on foreign manufacturers and in some cases pressed for decreased reliance on specific trading partners, including China. The commission also expressed concern that some of their investments in research are “not always translated into commercially exploited innovation,” and are instead “captured elsewhere.”
- The goal of the initiative is to “examine the need for legislative and non-legislative actions and EU investments,” the notice explained. “Legislative actions may encompass follow up to the initiatives which are already in preparation, such as the review of the legislation on medicines for rare diseases and children (Orphan and Paediatric Regulations), the legislation on fees for the European Medicines Agency. It could also include a targeted evaluation and subsequent review of the basic pharmaceutical legislation, and to the extent necessary, other legislative acts.”
- The comment period is open until July 7th, and the commission intends to adopt recommendations during the fourth quarter of this year.
3) India’s CDSCO says it will consider international data in support of vaccine approvals
By Alexander Gaffney, MS, RAC
India’s medical products regulator, the Central Drugs Standard Control Organization (CDSCO), issued new regulatory guidance last week indicating that it will consider both preclinical and clinical data generated outside of India in support of marketing approvals for COVID-19 vaccines.
- The move could help to accelerate the development of, and access to, vaccines in the country. Many countries generally require vaccines and medical products to be tested within their local populations before being approved, since genetic differences can result in differences in drug metabolization or present unique safety issues.
- Under the 2019 Clinical Trial Rules, while local trials for a new drug already approved outside of India are required, they may be waived by the Drugs Controller General of India (DCGI). However, the waivers are generally only given for drugs that have no major unexpected serious adverse event, or if several other criteria are met, such as a commitment to a Phase IV trial following marketing authorization.
- “Data generated outside India will be considered and examined and an abbreviated pathway may be considered for COVID 19 vaccine based on scientific rational and level of completeness of data in human trials in addition to satisfactory preclinical data,” CDSCO wrote.
- The guidance also includes a checklist for all additional pre-clinical information required for vaccine studies, including characterization of the vector, the expression levels of the protein, purification processes, and more.
4) UK’s MHRA issues guidance on 3D printing medical devices during COVID-19 pandemic
By Charles Friend
On Thursday the UK’s Medicine and Healthcare products Regulatory Agency (MHRA) issued guidance on using 3D printing to manufacture medical devices or component parts during the COVID-19 pandemic.
- Currently, devices manufactured in the UK must comply with current EU/EEA standards for medical devices. Devices in the UK are required to hold a CE mark, a certification mark indicating compliance with EU standards. This includes devices manufactured using additive manufacturing methods, such as 3D printing.
- The MHRA differentiates between 3D printed medical devices and PPE and has different requirements for each. The MHRA considers products intended to protect the wearer as personal protective equipment (PPE), while products intended to protect a patient are considered medical devices. 3D printed medical devices must meet requirements detailed in the Medical Devices Directive whereas 3D manufactured PPE must meet the requirements of PPE Regulation 2016/425. Products intended to protect both patients and healthcare workers also must meet PPE requirements.
- Firms and manufacturers using 3D printing to produce non-CE marked medical devices in the UK must apply to for an exceptional use authorization.
- Manufacturers are encouraged to use original parts when possible and meet the same safety standards as devices manufactured using normal manufacturing processes. The guidance detailed that manufacturers of medical devices should try to use original parts or those with the same specifications when possible. It also acknowledged that differences in material processing and processing requirements may introduce new risks, and stated that compliance with existing biological safety standards were essential.
5) Countries roll out emergency authorizations for COVID-19 drug remdesivir
By Alexander Gaffney, MS, RAC
The FDA isn’t the only global regulator offering speedy reviews and authorizations for investigational drugs for COVID-19.
- India approved the emergency use of Gilead’s remdesivir on June 1. South Korea approved emergency use of the drug on June 3. Japan had given approval to remdesivir under the country’s “exceptional approval pathway” back on May 7th. The US FDA issued an emergency use authorization for the drug on May 1st. The drug’s manufacturer, Gilead Sciences, has also granted distribution licenses to allow the drug to be distributed to 127 countries, assuming local regulatory approval.
- Other regulators like the European Medicines Agency (EMA) haven’t yet taken action. EMA head Guido Rasi said on May 18th that he expected that conditional authorization could be coming in “days” after initiating a rolling review of the drug on May 15th, but the Committee for Medicinal Products for Human Use (CHMP) has not yet released any authorization decision.
- For countries, the risk is being first—or last—to take action on a drug for COVID-19. A country that acts too early to authorize use of a drug could unwittingly subject their citizens to side effects associated with the drug’s use. If a regulator acts too late, they could be accused of withholding access to a drug out of an over-abundance of caution. The local needs of each country as their fight COVID-19 may also influence their tolerance for risk.
“A lot of companies seem under the impression that the move of the date of application means that all the other subsequent deadlines at the end moved up with one year too. Wrong! The other deadlines of May 2024 and May 2025 did not move at all.”
– Erik Vollebregt, a medical device-focused attorney with Axon lawyers, explaining how the delay in the Medical Device Directive due to COVID-19 has not have an effect on long-term deadlines associated with the directive, which was to have gone into effect last week.