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VCLS COVID-19 Update

We are closely monitoring the impact of COVID-19 on our industry and aim to bring you the very latest news from Regulatory Agencies around the world.  This page will be updated as soon as these updates are announced.

February 18th 2022

USA: FDA UPDATES

  • Treatments for COVID-19
    • On Dec 22, 2021, FDA authorized First Oral Antiviral for Treatment of COVID-19: FDA issued an emergency use authorization (EUA) for Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms or about 88 pounds) with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
    • On Dec 23, 2021, FDA authorized a second Oral Antiviral for Treatment of COVID-19: FDA issued an EUA for Merck’s molnupiravir for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate.
    • On January 21st, 2022, The FDA has expanded the approved indication for Veklury to include its use in adults and pediatric patients (12 years of age and older who weigh at least 40 kilograms, which is about 88 pounds) with positive results of direct SARS-CoV-2 viral testing, and who are not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.
    • On January 24th, 2022, the FDA revised the authorizations for two monoclonal antibody treatments – bamlanivimab and etesevimab (administered together) and REGEN-COV (casirivimab and imdevimab) – to limit their use to only when the patient is likely to have been infected with or exposed to a variant that is susceptible to these treatments. Because data show these treatments are highly unlikely to be active against the omicron variant, which is circulating at a very high frequency throughout the United States, these treatments are not authorized for use in any U.S. states, territories, and jurisdictions at this time. In the future, if patients in certain geographic regions are likely to be infected or exposed to a variant that is susceptible to these treatments, then use of these treatments may be authorized in these regions.
  • Vaccines/Prevention
    • New long-acting monoclonal antibodies for pre-exposure prevention of COVID-19 in certain individuals (link): FDA issued an emergency use authorization (EUA) for AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab and administered together) for the pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and pediatric individuals (12 years of age and older weighing at least 40 kilograms [about 88 pounds]). 2 requirements:
      • moderate to severely compromised immune systems due to a medical condition or due to taking immunosuppressive medications or treatments;
      • a history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines, therefore vaccination with an available COVID-19 vaccine.
    • On January 3rd, 2022, Amendment of the EUA for the Pfizer-BioNTech COVID-19:
      • Expand the use of a single booster dose to include use in individuals 12 through 15 years of age.
      • Shorten the time between the completion of primary vaccination of the Pfizer-BioNTech COVID-19 Vaccine and a booster dose to at least five months.
      • Allow for a third primary series dose for certain immunocompromised children 5 through 11 years of age.
    • On January 7th, 2022, FDA Shortens Interval for Booster Dose of Moderna COVID-19 Vaccine to Five Months
    • On January 31st, 2022, FDA approved the second COVID-19 vaccine: the vaccine has been known as the Moderna COVID-19 Vaccine; the approved vaccine will be marketed as Spikevax for the prevention of COVID-19 in individuals 18 years of age and older.

EUROPE: EMA UPDATES

  •  Treatments for COVID-19:
    • 7 treatments have been authorised by the EMA: Kineret, Paxlovid, Regkinora, RoActemra, Ronapreve, Veklury and Xevudy
    • 2 MAA have been submitted: Olumiant and Lagevrio
    • 1 MAA is currently under rolling review: Exusheld

October 19th 2021

USA: FDA UPDATES

  • Treatments for COVID-19
    • September 16th, 2021: The FDA revised the emergency use authorization (EUA) for bamlanivimab and etesevimab, administered together, to include emergency use as post-exposure prophylaxis (prevention) for COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death. Post-exposure prophylaxis with bamlanivimab and etesevimab, administered together, is not a substitute for vaccination against COVID-19.
  • Vaccines
    • Vaccine Booster:
      • August 8th, 2021: FDA Authorizes Additional Vaccine Dose for Immunocompromised People: FDA amended the emergency use authorizations (EUAs) for both the Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine to allow for the use of an additional dose in certain immunocompromised individuals, specifically, solid organ transplant recipients or those who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.
      • September 22nd, 2021: The FDA amended the EUA for the Pfizer-BioNTech COVID-19 Vaccine to allow for use of a single booster dose, to be administered at least six months after completion of the primary series in:
        • individuals 65 years of age and older;
        • individuals 18 through 64 years of age at high risk of severe COVID-19; and
        • individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.
      • August 23rd, 2021: the FDA approved the first COVID-19 vaccine, known as the Pfizer-BioNTech COVID-19 Vaccine, now marketed as Comirnaty (koe-mir’-na-tee), for the prevention of COVID-19 disease in individuals 16 years of age and older.
      • August 24th, 2021: The FDA updated the Pfizer-BioNTech emergency use authorization (EUA) to support the extension of shelf-life of the Pfizer-BioNTech COVID-19 Vaccine stored at -90 degrees to -60 degrees Celsius from 6 months to 9 months.

EUROPE: EMA UPDATES

  • Treatments for COVID-19:
    • 1 treatment has been authorised by the EMA (via CMA): Veklury (remdesivir)
    • 5 treatments received positive EMA opinion following referral procedure (Art. 5(3) of Regulation 726/2004)
      • 2 of them are under rolling review by the EMA – for now, only a recommendation has been established by the EMA to support national advice on the possible use of those treatments before a marketing authorization is issued.
    • 5 treatments under evaluation: Olumiant, Kineret, Ronapreve, Regkirona, RoActemra

COVID-19 vaccines:

  • Clinical data of approved vaccines are available on EMA’s website (login with EMA account)
  • Efficacy updates:
    • EMA agrees that third doses of mRNA vaccines (Comirnaty and Spikevax) may be given to people with severely weakened immune system at least 28 days after the second dose (based on studies in patients taking immunosuppressant drugs after organ transplant).
    • EMA concluded that a booster dose of Comirnaty given at least 6 months after the second dose is safe and increase sharply antibody titre to higher levels compared to what was been seen after 2nd dose. Therefore, it might be considered in the ongoing vaccination campaigns. However, no firm recommendations can be made at this stage on when and for whom to implement a booster dose. As of today, vaccines developers and health agencies are still trying to figure out how long last the second dose.
  • Safety updates:
    • EMA released communication to healthcare professional on cases of thrombocytopenia reported after Vyxzevria  and Covid-19 Vaccine Jenssen

News:

  • The European medicines regulatory network extended until the end of 2022 the validity of good manufacturing practice (GMP) and good distribution practice (GDP) certificates, and time-limited manufacturing, import and wholesale authorisations.
  • EMA extended its fee waiver on scientific advice for COVID-19 treatments and vaccines.
  • EMA staff (main author: Marco Cavaleri, chair of the Covid 19 task force) published in The Lancet an article on shaping EU medicines regulation after COVID-19, article available here.

July 30th 2021

USA: FDA updates

  • General:
    • The FDA has leveraged various tools, such as expediting reviews, exercising enforcement discretion and publishing guidances, with the goal of increasing patient access to medications in shortage or preventing potential shortages. The FDA is also working to implement the drug shortage-related provisions of the Coronavirus Aid, Relief, and Economic Security Act.
    • On July 8, 2021, the FDA hosted a Grand Rounds lecture about regulatory science research funded by the FDA: SARS-CoV-2 Host-Pathogen Interaction, Vaccines & Variants of Concern.
    • July 19 to 23, at the FDA SBIA REdI Annual Conference, FDA leaders reflected on the FDA’s use of Emergency Use Authorizations (EUAs) and other resources in making drug, device and biological products available to support the public health response to the COVID-19 pandemic.

Europe: EMA updates

February 3rd 2021

USA: FDA updates

  • Vaccines
    • 2 EUA have been issued by the FDA in December for COVID-19 vaccines from Pfizer/BioNtech and Moderna companies.
  • Treatments for COVID-19:
    • New Guidance: Potency Assay Considerations for Monoclonal Antibodies and Other Therapeutic Proteins Targeting SARS-CoV-2 Infectivity. (Jan 15th, 2021).
      • Goal: Potency assays are usually discussed with the FDA “over a span of years”. Given the urgency, FDA provides recommendations with the goal to “facilitate more complete submissions”.
      • Scope: This guidance applies only to mAbs and other therapeutic proteins designed to bind to viral receptors on host cells, inhibit viral entry, and/or elicit Fc-mediated effector function. Vaccines, hyperimmune globulins, gene therapies, cell therapies, and convalescent plasma are not within the scope of this guidance.
      • The potency assays to be considered will depend on the proposed mechanism of action. Example of assays per MoA:
        • BINDING ASSAYS:
          •  Usually an ELISA or SPR assay.
          • Established early in development, usually helpful in the initial phase of development, they do not confirm the ability to inhibit the target protein’s activity. For products that inhibit SARS-CoV-2 spike protein to ACE2, FDA recommends an inhibition assay.
        • VIRAL NEUTRALIZATION ASSAYS
          • = a more comprehensive way to assess both mechanisms of action and potency.
          • In vitro neutralization assays should be established early in the development process. The guidance walks developers through the steps of SARS-CoV-2 virus entry into cells and addresses key considerations for several types of viral neutralization assays.
        • Fc-EFFECTOR FUNCTION ASSAYS
          • “FDA recommends including a FcγRIIIa-mediated/natural killer cell antibody-dependent cell-mediated cytotoxicity assay, as that appears to be the most sensitive to changes in glycosylation”.
      • Additional consideration: the virus isolate or spike proteins used in the potency assay should reflect the isolates prevalent in the US; sponsors should provide genome sequences or GenBank IDs, a master cell bank of producer cells should be maintained, and other considerations.
  • Other Guidance:
    • New Guidance: Manufacturing Considerations for Licensed and Investigational Cellular and Gene Therapy Products During COVID-19 Public Health Emergency (Jan 19th, 2021)
      • Scope: CGT products. It does not apply to human cells, tissues, and cellular- or tissue-based products (HCT/Ps) regulated solely under section 361 of the PHS Act & medical devices under the FD&C Act.
      • Goal: Provide manufacturing considerations for licensed and investigational CGT products during the COVID-19 pandemic.
      • Background: No information regarding SARS-CoV-2 contaminating CGT products or being transmitted via these products. However, because SARS-CoV-2 is a novel coronavirus, CGT manufacturers need to ensure compliance with CGMP requirements by determining if there are any new risks with the manufacturing process.
      • FDA recommends a risk assessment and mitigation strategy for CGT product manufacturing be submitted to the FDA. Supported with scientific justification and literature references. One key consideration is the potential for accidental expansion of the SARS-CoV-2 virus during cell culture.
      • Donor Assessment: FDA advises continuation of routine screening measures: manufacturers should assess whether in the last 28 days the donor was (allogeneic or autologous) in close contact with an individual diagnosed or suspected of having COVID-19; diagnosed or suspected of having COVID-19.; or positive test but never developed symptoms.
      •  Cellular and tissue source material: Manufacturers should consider the known characteristics of SARS-CoV-2, including tissue tropism and infection/propagation during the manufacturing process. SARS-CoV-2 is a respiratory virus; therefore, the manufacturer should mitigate the risk of infection by considering the organ system from which the donor cells are recovered from.
      • Material testing: No recommendations for testing of CGT material but can be added by the manufacturer to their risk mitigation strategy. Manufacturers’ quality unit should approve all evaluations and document them in the quality management system.
  • Added content in the Q&A of the guidance “Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency”

 

Europe: EMA updates

  • COVID-19 treatments:
    • 2 treatments have been authorized in the EU, 1 treatment is under evaluation by the EMA.
Treatment Status
Dexamethasose Use endorsed following referral procedure
Veklury (remdesivir) Conditional marketing authorization (CMA) granted
REGN-COV2 antibody combination (casirivimab/ imdevimab) Rolling review started on Feb. 1

 

  • COVID-19 vaccines:
    • 3 COVID-19 vaccines have been authorized in the EU (via CMA), 1 rolling review is ongoing:
Vaccine Vaccine developer Stage
Comirnaty (BNT162b2) BioNTech, in collaboration with Pfizer CMA granted (1st safety update published)
mRNA-1273 Moderna Biotech Spain, S.L. CMA granted
ChAdOx1-SARS-CoV-2 AstraZeneca, in collaboration with the University of Oxford CMA granted
NVX-CoV2373 Novavax CZ AS Rolling review started on Feb. 3

 

  • Guidance:
    • Pharmaceutical quality: EMA published guidance for developers of COVID-19 vaccines and treatments on where to find the standards and requirements related to pharmaceutical quality that are applicable in the EU.
    • Packaging and labelling: EMA published a Q&A guidance on flexibilities to help developers of COVID-19 vaccines prepare and roll out packaging and labelling for their vaccines quickly.

 

November 25th, 2020

USA: FDA updates

  • Treatments for COVID-19:
    • On October 22, 2020, the FDA approved the first treatment for COVID-19: Remdesivir (Veklury®) for use in adult and pediatric patients 12 years of age and older for the treatment of COVID-19 requiring hospitalization.
    • On November 9, 2020, the FDA authorized monoclonal antibody for treatment of COVID-19, through an emergency use authorization (EUA) for bamlanivimab.
    • On November 19, 2020, the FDA issued an EUA for the drug baricitinib, in combination with remdesivir, for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
  • Diagnostic / Medical Device:
    • On November 6, 2020, the FDA authorized the first serology test that detects neutralizing antibodies from recent or prior SARS-CoV-2 Infection. The FDA issued an emergency use authorization (EUA) for the cPass SARS-CoV-2 Neutralization Antibody Detection Kit, which specifically detects this type of antibody.
    • On November 17, 2020, the FDA authorized the first COVID-19 Test for self-testing at Home with an EUA for Lucira COVID-19 All-In-One Test Kit (nasal swab samples).

Europe: EMA updates:

  • EMA Public Meeting:
    • EMA will organise a public meeting on 11 December 2020 to inform European citizens about the EU regulatory processes for the approval of COVID-19 vaccines. You will find more information on the EMA website.
  • COVID-19 treatments:
    • 2 treatments have been authorised in the EU, 1 treatment is under evaluation by the EMA.

Covid-19 treatment

  • COVID-19 vaccines:
    • 3 rolling reviews are currently ongoing:

  • Guidance:
    • EMA and the national competent authorities have prepared a safety monitoring plan for COVID-19 vaccines. Guidance is also available on preparing risk management plans for COVID-19 vaccines.
    • EMA published guidance for developers of potential COVID-19 vaccines on the clinical evidence to include in their MAA.

October 8th, 2020

The FDA just released a guidance on the emergency use authorization for vaccines to prevent COVID-19.

A few highlights:

  • The criteria for an EUA and recommendations for regulatory, CMC, safety and effectiveness information. FDA is expecting in an EUA request
  • Clarifications about the circumstances under which the issuance of an EUA would be appropriate
  • Requirements to continue the sponsor’s phase III studies after requesting the EUA and continue to collect placebo-controlled data in any ongoing trials

October 1st, 2020

USA: FDA updates

  • New Q&A from the FDA related to Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency in August 2020. FDA is issuing this guidance to provide answers to frequently asked questions about regulatory and policy issues related to inspections, pending drug applications, and changes in manufacturing facilities for approved pharmaceutical products.
  • The FDA has issued an Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment.
  • On Sept 11, FDA issued a temporary guidance, “Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency,”  to help drug and biological product manufacturers (including animal drug manufacturers) transition from operations impacted by the COVID-19 public health emergency to normal manufacturing operations. This guidance provides recommendations to help manufacturers prioritize products as they resume normal operations and as they remediate current good manufacturing practice (CGMP) activities that were necessarily delayed, reduced, or otherwise modified during the public health emergency in order to maintain production and the drug supply.
  • FDA News release on Aug 28: FDA Broadens Emergency Use Authorization for Veklury (remdesivir) to Include All Hospitalized Patients for Treatment of COVID-19.
  • Press Release on Aug 28: FDA Announces Advisory Committee Meeting to Discuss COVID-19 Vaccines. The U.S. Food and Drug Administration announced that a public meeting of the Vaccines and Related Biological Products Advisory Committee will be held on Oct. 22, 2020, to discuss the general matter of the development, authorization, and/or licensure of vaccines indicated to prevent COVID-19.

Europe: EMA updates

  • Treatments and vaccines for COVID-19
    • As of September 2, EMA had finalised 17 scientific advice procedures for potential medicines to treat COVID-19, with a further 22 ongoing. It had also been in contact with the developers of 158 potential COVID-19 treatments and 38 potential COVID-19 vaccines.
    • EMA has endorsed the use of dexamethasone for the treatment of hospitalised adults and adolescents patients with COVID-19 who are receiving respiratory support.
  • EMA’s governance during COVID-19 pandemic
    • EMA decided to continue holding its committee and working-party meetings and its stakeholder events virtually until the end of 2020.

August 10th, 2020

USA: FDA updates

  • Vaccines for COVID-19: The FDA took important action to help facilitate the timely development of safe and effective vaccines to prevent COVID-19 by providing guidance with recommendations for those developing COVID-19 vaccines for the ultimate purpose of licensure. This guidance provide requirements for CMC, NC and Clinical considerations. To ensure that a widely deployed COVID-19 vaccine is effective, the primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at least 50%.
  • The FDA released an ‘update’ on the CTAP program on July 14th
  • Diagnostic tests: On July 31, FDA authorized the first tests that estimate a Patient’s Antibodies from Past SARS-CoV-2 Infection. Both tests from Siemens, the ADVIA Centaur COV2G and Atellica IM COV2G, are what are known as “semi-quantitative” tests, meaning that they do not display a precise measurement, but estimate the quantity of a patient’s antibodies produced against infection with the virus that causes COVID-19.
  • FDA Insight podcast : FDA share some insights into issued facing the agency on the COVID-19 pandemic, including discussion around vaccines and treatments.

Europe: EMA updates

  • Treatments and vaccines for COVID-19
    • EMA is applying exceptional transparency measures for treatments and vaccines against COVID-19 that are approved or are under evaluation, to address the high interest in information on COVID-19 medicines and to support global research.
    • As of July 31, EMA had finalised 17 scientific advice procedures for potential medicines to treat COVID-19, with a further 15 ongoing. It had also been in contact with the developers of 154 potential COVID-19 treatments and 38 potential COVID-19 vaccines.
    • The European Commission granted a conditional marketing authorisationfor Veklury (remdesivir), for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. Veklury is the first treatment against COVID-19 in the EU.
  • Guidance for medicine developers and companies on COVID-19
    • The European Medicines Agency (EMA) is providing guidance for medicine developers and pharmaceutical companies to help speed up medicine and vaccine development and approval for COVID-19, and on how they should address the regulatory challenges arising from the COVID-19 pandemic.
    • EMA urged researchers to adhere to the latest revision of the ENCePP Guide on methodological standards in pharmacoepidemiology. The foreword highlights chapters relevant to COVID-19 and examples of good practice.
    • Regulators have agreed on acceptable clinical-trial endpoints to facilitate rapid and consistent clinical trials for COVID-19 treatments (see report from the International Coalition of Medicines Regulatory Authorities).

Europe: National authorities updates

  • For product related to COVID-19, BfArM offers free scientific advice procedures for pharmaceuticals and medical devices, free applications for approval of clinical trials of drugs and medical devices and free applications for special approval of medical devices. All Scientific advices are conducted via conference calls.
  • The ANSM will issue their decisions electronically.

June 29th, 2020

After a 3-month public consultation, the EMA and Biostatistics Working Party (BSWP) published on June 26th the final version of its guidance titled “Points to consider on methodological aspects of ongoing trials impacted by Covid-19”.

In this guidance, the BSWP, acknowledging the impact of the coronavirus disease (COVID-19) on trial participants as well as on the methodological aspects of ongoing trials, raises major points for consideration to Sponsors whose ongoing trials are or might be affected.

Those major points are related to the capture of systematic deviations due to COVID-19, the data collection and the risk-assessments to be made regarding the impact of the COVID-19 potentially affecting trial participants directly as well as the COVID-19 related measures affecting the clinical trial conduct on trial integrity and interpretability. The guidance also advises on the potential follow-ups based on the risk-assessments that may lead to substantial changes in the design or conduct of the concerned trials.

A summary of  responses to questions raised by stakeholder during this consultation presented by common themes along with a brief outline on how BSWP addressed the comments in the updated version of the guidance is also available.

June 2nd, 2020

The FDA published today a new guidance titled Institutional Review Board (IRB) Review of Individual Patient Expanded Access Requests for Investigational Drugs and Biological Products During the COVID-19 Public Health Emergency Guidance for IRBs and Clinical Investigators. 

The FDA is issuing this guidance because of the substantial increase in the number of requests by physicians seeking to treat their patients with investigational drugs under the agency’s individual patient expanded access (EA) pathway during the COVID-19 public health emergency.  The agency also is aware that IRBs seek clarity regarding the key factors and procedures to consider when they review requests for individual patient EA — including reviews conducted by a single member of the IRB — to fulfill obligations under 21 CFR Part 56.

The recommendations in the guidance address establishing procedures for single IRB member review in response to physician waiver requests for exemption from full IRB review, as well as factors to consider when assessing benefits and risks for a particular patient being treated under expanded access.

The FDA takes steps to streamline development of tests with at-home sample collection, by including a voluntary EUA template for at-home sample collection kits to its website.

April 20th, 2020

The National Institutes of Health (NIH) announced on April 18th a new initiative to accelerate the development of treatments for COVID-19 involving the US Food and Drug Administration (FDA) and other US health agencies, the European Medicines Agency (EMA) and 16 drugmakers in order to develop a coordinated research strategy & coordinate clinical trials and regulatory processes. More info here.

The American Medical Association (AMA) has also issued recommendations to address COVID-19 pandemic, such as:

  • Expand telemedicine, by allowing coverage of telemedicine, permit telemedicine for first-time visits and providing coverage and payment for COVID-19 related telemedicine visits.
  • Expand Medicaid coverage, by establishing special enrolment periods to any uninsured state resident with COVID-19 related diagnoses or symptoms and by requiring insurers/employers to continue coverage for employees under group policies even if the employee would others be ineligible due to decrease in hours worked.
  • Access to medication, by waiving time restriction on prescription refills and authorize payment to pharmacies for up to 30 days’ supply, by removing restrictions on the Medicaid preferred drug lists to help avoid medication shortage
  • Reduce patient out of pocket regarding access to care for treating COVID-19 symptoms, by ensuring coverage for the cost of care related to COVID-19 (diagnostic testing and care), by covering the costs of vaccination with no cost-sharing when vaccines will be available

April 16th,2020

FDA updated the COVID-19 related Guidance Document that includes Guidance for Industry, Investigators, and IRBs today 16 April 2020.

From what we can tell, the body of the text was maintained with only minor editorial changes including change of the term “Pandemic” to “Public Health Emergency” and some additional abbreviations were defined.

7 Questions and Answers were added to the document beginning on page 16 – Pasted below for your quick scan of applicability to your projects:

  • Q11. How do I obtain informed consent from a patient unable to travel to a clinical trial site where electronic informed consent is not an option?
  • Q12. What factors should sponsors consider when deciding whether to implement remote performance outcome (PerfO) assessments or interview-based clinician-reported outcome (ClinRO) assessments during the COVID-19 public health emergency?
  • Q13. I am a study monitor and am unable to conduct on-site monitoring visits due to the COVID-19 public health emergency. May I remotely perform the site monitoring visit? What recommendations does FDA have for how I can remotely perform source document review?
  • Q14. I am a sponsor of commercial INDs and electronic common technical document (eCTD) requirements cannot be met due to the COVID-19 public health emergency. Who do I contact for assistance?
  • Q15. During the COVID-19 public health emergency, certain patients may no longer be able to travel to a central location for protocol-based treatment that is scheduled on a recurring basis. Can the investigational product intend for infusion to be shipped to a local health care provider who is not a sub-investigator to administer the infusion to a patient while still maintaining the integrity of the trial? If so, what else would be needed regarding trial monitoring and institutional review board (IRB) oversight?
  • Q16. If a subject is unable to receive the investigational drug from the trial site but the product is FDA-approved for other uses, can the patient or health care provider secure the product commercially or is this considered the sponsor charging for the investigational drug under 21 CFR 312.8? Can the sponsor reimburse trial subjects for their out of pocket expenses in getting the drug commercially?
  • Q17. Throughout the guidance, FDA recommends that sponsors consult with the review division for certain changes to ongoing clinical trials. For drugs and biologics, is this a reference to scheduling a Type A meeting? How should sponsors contact the FDA regarding device clinical trials?

More info here: https://www.fda.gov/media/136238/download

April 09, 2020

How does COVID-19 impact payers and HTA decision-making processes around the world? What are the consequences for companies currently developing drugs that undergo pricing and reimbursement appraisals?

Here is a summary of the latest updates for HTA and pricing assessments from key international markets:

EU 27: EunetHTA The European HTA network will prioritize the needed resources to be used in their various national settings in order to respond to the current emergency on COVID-19.

Therefore, Assessments or Early Dialogues might face delays or suspension of new requests.

https://eunethta.eu/eunethta-response-to-covid-19/

France: Haute Autorité de Santé (HAS), Ministry of Health

The HAS will prioritize COVID-related drug and medical devices assessments for its HTA assessment and continues review of other products based on the criteria of importance to patient care.

When it comes to new product pricing, the French government’s Economic Committee for Health Products (CEPS) ensures the continuity of its pricing activities and economic regulation of health products.

Germany: Gemeinsamer Bundesausschuss (G-BA), Ministry of Health

The G-BA has not announced any prioritisations or limitations to early benefit assessment processes (drugs & devices) – virtual meetings and written decision making are employed to support continuity.

However, potential capacity problems to review and set up pre-AMNOG early advice sessions for manufacturers have been identified:

  • Potential for delays for new applications
  • G-BA is aiming to keep all scheduled sessions (via teleconference)

At the same time, the Ministry for Health is planning to push ahead of the introduction of the digital health reimbursement process as scheduled for this summer.

Italy: Agenzia Italiana del Farmaco (AIFA)

The Italian Medicines Agency keeps to its scheduled committee meetings including pricing and reimbursement meetings (Price and Reimbursement Committee [CPR], Comitato Tecnico Scientifica ([CTS]). The meetings will be schedule remotely, and a Coronavirus crisis committee with CTS support will prioritize the COVID-19 appraisals (guidance, treatment, etc).

The minutes of the latest Price and Reimbursement Committee (CPR) meeting of April 1st have just been made available this week

Spain: Agencia Espanola de Medicamentos y Productos Sanitarios  (AEMPS), Ministerio de Sanidad

The AEMPS Coordination group for therapeutic positioning assessment (IPT group) does not report delays or cancellations of meetings to review a new product or indication use at this moment.

The AEMPS has also established a series of special measures to speed up and prioritize the evaluation procedures for biocide products. These measures aimed at simplifying the authorization procedure respond to the need to avoid the shortage of this type of hydroalcoholic solutions in the health centers of our country

Equally, to support continuity, the Ministry of Health pricing commission (Comisión Interministerial de Precios de Los Medicamentos [CIPM]) does not report any delays or cancellations for the pricing/reimbursement.

UK: National Institute for Health and Care Excellence (NICE)

NICE has announced that only therapeutically critical assessment, COVID 19 diagnostic or therapeutic and cancer medicine will be undertaken. The technology appraisal committee meeting is continuing to be held virtually.

The agency also provides free fast track scientific advice for companies developing novel diagnostics or therapeutics for COVID-19.

US

ICER assessment is still ongoing but with timelines delayed by 3 months due to external stakeholders involved in the COVID-19 pandemic. Some public meetings are postponed indefinitely (Sickle Cell Disease and Cystic Fibrosis).

To support appropriate care in the COVID19 crisis, CMS puts in place various waivers and flexibilities for hospitals, other healthcare facilities, providers enrollment (advance payment), state Medicaid agencies (1135 waivers), 1915 (c) Appendix K Waivers.

April 08, 2020

EMA:

Since the end of March and the beginning of April, the EMA continues to perform discussions with medicines developers on potential treatments and on vaccines against COVID-19. EMA encourages industries to launch clinical trials to generate conclusive evidence in order to market as quickly as possible an effective treatment in Europe. In the same logic, still, to become more efficient in the management of the sanitary crisis, a new coordination group named COVID-19 EMA pandemic Task Force (COVID-ETF) was created. This Task Force group is helping the EU Member States and the European Commission to take quick and coordinated regulatory action on the development, authorization and safety monitoring of treatments and vaccines intended for the treatment and prevention of COVID-19. This working group will also assist the EMA’s scientific committees or take part on behalf of the scientific committee’s discussion with drug developers. The main functions of COVID-ETF are the following:

  • the review of available scientific data on COVID-19 medicinal products and identify promising candidates;
  • the request data from developers and engage with them in preliminary discussions;
  • to be the scientific support in collaboration with the CTFG to facilitate clinical trials conducted in the EU for the most promising medicinal products for COVID-19;
  • to provide feedback on development plans of COVID-19 medicinal products when formal rapid scientific advice is not feasible;
  • to act as an advisor to the Scientific Advice Working Party (SAWP) or the CHMP for formal scientific advice and product-related assessment and contribute to the PRAC activities on emerging safety issues related to COVID-19;
  • to ensure close cooperation with stakeholders and relevant European and international organizations.

In addition to the different reflection and working groups put in place, the EMA keeps releasing strong recommendations at the attention of developers regarding the conduction of clinical trials and compassionates uses. After the Guidance on the management of clinical trials during the COVID-19 (coronavirus) already highlighted by VCLS in a previous post, the new guidance on the conduction of the compassionate use of remdesivir for COVID-19 is a first relevant example which shows how the common approach regarding the criteria and use conditions is essential for driving a study.  In another vein, as the pandemic affects the issue of printed certificates for human and veterinary medicines by the authority, the EMA decided to provide electronic and authenticated certificates. With its efforts to digitalize its administrative processes for all documents requiring a signature, the European agency is considering whether the electronic signature should be implemented instead of keeping the handwritten signature. In conclusion, we would like to reassure you, EMA decided to stay available during EMA’s Easter break from 9 to 13 April 2020.

FDA:

From the US side, since April the FDA is really focused on the development of recommendations for keeping safe the blood collection/transfusion and derived blood product supply. The American agency published new guidance regarding blood Supply in the US: Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency. This guidance proposes to ensure adequate protections for donor health and maintaining a safe blood supply. In the same line, specific recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19 are available. Indeed, the guidance for industry named: Investigational COVID-19 Convalescent Plasma raises and answers to the following points:

  • which IND regulatory pathways should implement for Use of Investigational COVID-19 Convalescent Plasma;
  • the different criteria which need to be fulfilled in term of patient eligibility;
  • which information about COVID-19 Convalescent Plasma should be collected and reflected in IND application;
  • how records for the COVID-19 convalescent plasma unit must be maintained.

In another topic, FDA issued as other agencies around the world, a policy to oversee serological tests development and to remind that developers must perform the appropriate evaluation to determine that their tests are accurate and reliable. In the emergency situation, no prior FDA review before marketing tests is mandatory certain conditions outlined in the guidance document are met.

Many other guidance to facilitate the availability of drugs and devices in specific areas was released. Regarding the repurposing of medicines, the FDA is the first agency that approved a marketing application for Hydroxychloroquine Sulfate in COVID-19. This first approval demonstrated that the repurposing of drugs should not be left out for the only benefit of new drugs development, but also be taken into account and used as a weapon in the COVID-19 fight.

Stronger together: International Coalition of Medicines Regulatory Authorities

VCLS also wants to underline that regulators have published a report highlighting their considerations on the development of potential COVID-19 therapeutics, clinical trials, and compassionate use programs. The report provided international positioning on progress on COVID-19 medicine development with a focus on the clinical trials and compassionate use ongoing and especially the availability of potential COVID-19 treatments. The complete report is available here.

April 1, 2020:

FDA updated the Guidance on Conduct of Clinical Trials of Medicinal Products during COVID-19 Pandemic on March 27, 2020 with an informative Q&A Appendix on clinical trial conduct, including questions and answers such as:

  • What are some of the key factors that a sponsor should consider when deciding whether to suspend or continue an ongoing study or to initiate a new study during the COVID-19 pandemic?
  • What key factors should sponsors consider when deciding whether to continue administering or using an investigational product that appears to be providing benefit to the trial participant during the COVID-19 pandemic?
  • How should a sponsor submit a change in protocol that results from challenges related to the COVID-19 pandemic?

FDA has also created a special emergency program for possible therapies, the Coronavirus Treatment Acceleration Program (CTAP). It uses every available method to move new treatments to patients as quickly as possible. There is no equivalence in the EU yet, but some countries such as the ANSM proposed some dedicated pathways to expedite new treatment against COVID-19.

March 30, 2020:

FDA has released a FAQ document (March 24th) regarding the investigational use of COVID-19 Convalescent Plasma in emergency INDs. From the FDA website:

“One investigational treatment being explored for COVID-19 involves the use of convalescent plasma collected from recovered COVID-19 patients. It is possible that convalescent plasma that contains antibodies to SARS-CoV-2 (the virus that causes COVID-19) might be effective against the infection.”

“FDA is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections through the process of single patient emergency Investigational New Drug Applications (eINDs) for Individual patients under 21 CFR 312.310.”

Learn more about our Regulatory solutions.

Impact on ongoing clinical trials

If you are currently conducting clinical trials in the EU, please be informed that the EMA, in collaboration with the Clinical Trials Expert Group (CTEG) of the European Commission, the Clinical Trials Facilitation and Coordination Group (CTFG)  and the GCP Inspectors’ Working Group, has published a harmonized guidance document on how to manage clinical trials during the COVID-19 pandemic, available here. In addition to this guidance document, Competent Authorities have already published specific instructions on how to conduct clinical trials in their countries during this time. In some cases, these national guidelines will take priority over the European harmonized recommendations.

Several Competent Authorities are asking sponsors to perform a risk assessment and prepare a mitigation plan for their ongoing studies, taking into consideration the following points:

  • Initiation of new clinical trials or inclusion of new patients in ongoing clinical trials should be critically assessed
  • Changes to the shipment of the IMP: shipment to the patient’s home when possible and allowed by national legislation and data protection regulations
  • Changes to the treatment administration and study assessments
  • Changes to monitoring: postponing source data verification, remote monitoring if no additional burden to the sites, etc.
  • Temporary suspension of recruitment or treatment (when the sites are closed due to the quarantine measures, for instance).
  • Discontinuation of study subjects, if they cannot complete the key evaluations or adhere to critical mitigation steps etc.
  • Protocol deviations (which may occur more often in this period) should be thoroughly documented: some authorities have asked for a summary report on all deviations that occurred during the COVID-19 pandemic
  • The circumstances in which the implementation of an Urgent Safety Measure may be deemed necessary.

Delays should be expected in the review timelines of initial applications and amendments not related to COVID-19 (which do not impact the safety of the subjects) due to the staff limitations in most of the Competent Authorities and Ethics Committees. Furthermore, some of them have started to accept and encourage electronic submissions in the context of the COVID-19 pandemic.

As the situation is evolving rapidly, VCLS is keeping an up-to-date list of the Competent Authorities and Ethics Committees having published specific recommendations both in Europe (EU and non-EU countries) and worldwide (USA, Canada, Israel, South-Africa, etc.). Most of these guidelines have been issued without prior public consultation, therefore some specific issues encountered by sponsors may not be covered. Our team at VCLS is ready to take a close look at your needs and create tailored solutions for preserving patient safety and data integrity on your studies in these challenging circumstances.

Learn more about our Clinical Submission and Operation capabilities.

Call for new treatments for COVID-19

At the same time, many authorities worldwide have emphasized the need to prioritize the development of new treatments against this public health threat, advising on including COVID-19 related endpoints to ongoing clinical trials or pooling research resources into large multi-center, multi-arm clinical trials to generate sound evidence (see EMA call here).

Some of the Competent Authorities and Ethics Committees are proposing a rapid assessment of clinical trial applications related to the prevention of the infection or to the management of COVID-19 patients.

Our experts are here to help you guide the planning, design, conduct and reporting of clinical trials in order to accelerate the development of potential COVID-19 treatments.

March 23, 2020:

Many of you may be concerned about the impact of COVID-19 in the testing for human cells, tissues, or cellular and tissue-based products (HCT/Ps). The FDA has released a Q&A document that can be beneficial to understand their recommendations at this time. At VCLS, we are monitoring the situation closely and we are providing recommendations to our clients based on our most recent experiences. We strongly advise following FDA’s recommendations on implementing screening measures as a precaution to patients and healthcare providers. Please see below the extracted information from the Agency:

Q: Can COVID-19 be transmitted through human cells, tissues, or cellular and tissue-based products (HCT/Ps)?

A: Respiratory viruses, in general, are not known to be transmitted by implantation, transplantation, infusion, or transfer of human cells, tissues, or cellular or tissue-based products (HCT/Ps). The potential for transmission of COVID-19 by HCT/Ps is unknown at this time. There have been no reported cases of transmission of COVID-19 via HCT/Ps.
Routine screening measures are already in place for evaluating clinical evidence of infection in HCT/P donors.

Q: Is the FDA recommending that establishments implement screening measures for the deferral of HCT/P donors of who may be at risk of having COVID-19?

A: The HCT/P establishment’s responsible person must evaluate a prospective donor and determine eligibility (21 CFR 1271.50). Based on the limited information available at this time, establishments may wish to consider the following donor history in the 28 days prior to HCT/P recovery for persons who have:

  • traveled to areas with COVID-19 outbreaks, as defined by CDC
  • lived with individuals diagnosed with or suspected of having COVID-19 
  • been diagnosed with or suspected of having COVID-19

More details are available here: FDA emergency preparedness and response to COVID-19

March 19, 2020

The FDA released a guidance for industry, investigators and institutional review boards conducting clinical trials during the coronavirus (COVID-19) pandemic.

From the Clinical Trials perspective:

If you are currently conducting clinical trials in the EU and especially in the UK, Italy and the Netherlands, please be informed that Authorities have recently released communications on recommendations to follow in clinical trials’ submissions and conduct.

Please see links from MHRA and HRA in the UK, AIFA in Italy (English rough translation attached) and the CCMO in the Netherlands.

We recommend our clients to take consideration of putting the following measures in place, and in many cases will need to be reported/submitted to Competent Authorities/Ethics Committees in a timely manner:

  • IMP shipped to the patient’s home;
  • Administrations performed at home;
  • Visits/ assessments performed at home, including recording in source documentation;
  • Modifications in monitoring (potentially remote);
  • Temporary suspension of recruitment or treatment (e.g. if sites are entirely closed);
  • Discontinuation of study subjects, if they cannot complete key evaluations or adhere to critical mitigation steps; etc.

Competent Authorities and Ethics Committees are progressively sharing information on the conduct of clinical trials during this period, and which submissions are required for the exceptional measures put in place.

At VCLS, we are monitoring the situation daily, including communications from the Competent Authorities/Ethics Committees on this topic, and its potential impact on your ongoing activities.

Learn more about our Clinical Trial Operation capabilities.

March 18, 2020

From the EU perspective:

  • EMA has said as a precautionary measure, all EMA committee meetings and working parties will be held virtually until the end of April 2020. In addition, stakeholder events hosted by EMA which were planned to take place at the Agency’s premises in Amsterdam in March and April will either be held virtually or postponed until later in the year. Participants of these meetings will be informed directly about this decision.
  • EU Regulatory Stakeholders may also adjust their activity accordingly. Further country-specific information can be found via the country specific links.
  • Most EMA staff are working remotely, and this is expected to last until the end of April. These measures do not impact the EMA’s core activities so far. We shall keep you posted on any development on this front.

From the USA perspective:

  • The FDA is postponing most foreign inspections through April, effective immediately. Inspections outside the U.S. deemed mission-critical will still be considered on a case-by-case basis. The FDA based this decision on a number of factors, including State Department Level 4 travel advisories in which travel is prohibited for U.S. Government employees, Centers for Disease Control and Prevention travel recommendations, access restrictions being imposed on foreign visitors by certain countries, guidance from the Office of Personnel Management and the importance of the health and safety of its employees.
  • No one is traveling to the FDA for meetings. The meeting format was changed late last week to teleconferences call only. Our understanding is that most, if not all of FDA staff are working remotely. Our recent experience is that the FDA staff is calling from one line although they are all participating remotely. It gives them the possibility to conference call prior to calling the Sponsor and the option to put the Sponsor on hold, so they can have an internal discussion if needed.

March 13, 2020

Current events around the spread of the COVID-19 virus and its impact on the global economy continue to evolve. Voisin Consulting Life Sciences (VCLS) would like to reassure you that we continue to provide the same high-quality service during this difficult period.

We are monitoring the situation closely and constantly take appropriate actions to protect our employees to ensure business continuity. Please keep us informed of any steps or business restrictions your company takes that will impact the way we work with you so that we can make any necessary adjustments to our plans to stay on track.

Our focus, dedication and support are unwavering and we hope you and your closed ones remain safe and healthy.

 

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