Beyond the need to address the ongoing pandemic itself, regulators also must address the impacts to clinical trials as well as essential supplies of treatments and medicines for other diseases and conditions. In this final blog post of our series, we describe strategies to minimize disruption to ongoing clinical trials, drug manufacturing and essential supplies of blood and organs.
So far in our blog series, Monia Tumminello, Manager, Cortellis Regulatory Intelligence™, and Jaime Polychrones, Medical Writer, Cortellis Regulatory Intelligence, outlined:
- therapeutic development, helping to reduce the mortality rate and improve patient outcomes;
- the ongoing need for testing, contact tracing and personal protective equipment.
In this final blog post, we describe strategies to minimize disruption to ongoing clinical trials, drug manufacturing and essential supplies of blood and organs. Recognizing that this is unlikely to be the last infectious disease outbreak that the world will experience, governments have also outlined their plans for greater preparedness for the future.
Minimizing disruption to ongoing clinical trials
To address potential concerns about how clinical trials for other medications can continue amid the quarantines, site closures, travel limitations, interruptions to investigational product supply chains and potential personnel and participant infections occurring during the pandemic, the Food and Drug Administration (FDA) published and has since updated guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Pandemic. In addition,he European Commission (EC), European Medicines Agency (EMA) and national Head of Medicines Agencies (HMA) published the Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic. These challenges could impact trial conduct, such as completion of trial assessments, completion of trial visits and the provision of investigational medicinal products (IMPs).
With the FDA’s guidance, clinical trials conducted in the U.S. can continue with adjustments to conditions or protocols while still adhering to U.S. regulations and ensuring patient safety.
The guidelines include information about how to address protocol modifications or deviations, such as:
- assuring the safety of trial participants,
- maintaining compliance with Good Clinical Practice (GCP), and
- minimizing risks to trial integrity.
Trial participants should be kept informed about changes to any studies in which they are participating.
Since patient safety is the primary concern, sponsors should determine whether it is safer for patients to participate in safety assessments via phone, virtual visits or an alternative location, if acceptable for the trial.
Sponsors should notify institutional review boards (IRBs)/independent ethics committees (IECs) as soon as possible about changes in protocol. If participants’ wellbeing or lives are in jeopardy, such changes may be implemented without IRB approval but must be reported afterward. Sponsors should consult with the appropriate review division to discuss efficacy assessments if there are protocol modifications.
In addition, delays may be appropriate, or sponsors may choose to halt recruitment or withdraw participants. The agency recommends that sponsors should describe the following in appropriate study report sections or in a separate document:
- contingency measures implemented;
- a list of all participants affected by COVID-19–related study disruption and how their participation was affected; and
- analyses of the impact of contingency measures on the safety and efficacy results reported.
Practical considerations surrounding IMP include whether it can be administered and stored at the participant’s home, how the product stability will be maintained during transit, how safe custody of the product will be ensured and how IMP accountability and the evaluation of treatment compliance will be managed.
For clinical trials currently being established, the FDA recommends revising or creating policies and procedures to describe how participants will be protected during the pandemic and how trial conduct will be managed during possible disruption. This would include the impact on informed consent, study visits, data collection, study monitoring, adverse event reporting and possible changes to staff due to COVID-19 illness.
Approvals of medications include those for cancers, Alzheimer’s disease and HIV.
Beyond COVID-19, the regulatory agencies continued to review applications for the approval of other medications important for treating disease, such as:
- a new indication for avelumab for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy;
- PHESGO, a combination of pertuzumab, trastuzumab and hyaluronidase, that can be administered at home by a healthcare professional, injected under the skin for HER2-positive breast cancer;
- capmatinib, the first targeted treatment for adult patients with non-small cell lung cancer (NSCLC) that has spread to other parts of the body;
- flortaucipir for use with positron emission tomography (PET) imaging of the brain in adult patients with suspected Alzheimer’s disease;
- dolutegravir in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients;
- and more.
Substances of Human Origin (SoHO): maintaining a safe, sufficient and accessible supply
Safety measures related to COVID-19, including social distancing, resulted in a decrease in the donated supply of blood products and other Substances of Human Origin (SoHO). In addition, there was some concern about the presence of the COVID-19 virus in blood and bodily fluids that could be transmitted via transfusion or implantation.
Blood products and other Substances of Human Origin (SoHO) have been in short supply due to stay-at-home orders and concerns about presence of SARS-CoV-2 virus in blood and bodily fluids.
To address the short supply of SoHO, the FDA issued guidance revising the recommendations about the risk of transfusion-transmitted HIV and malaria and describing alternative procedures for blood and blood components, such as reducing the required quarantine time, to improve availability while helping to ensure adequate protections for donor health and maintaining a safe blood supply for patients. In addition, given the reported presence of the virus in fecal matter, the FDA also provided safety precautions for fecal microbiota transplantation in clinical trials and patient care.
The European Centre for Disease Prevention and Control (ECDC) also published a guidance document on COVID-19 and SoHO that aims to provide risk assessment and management options for the safe and sustainable supply of SoHO. This guidance analyzes the risks posed by COVID-19 to blood and organ transplant recipients, to the sufficiency and sustainability of SoHO supply and consider precautionary actions to mitigate the microbial safety of SoHO.
As convalescent plasma emerged as a potential therapeutic for COVID-19 patients, both agencies developed and released guidance on the donation, collection, testing, processing, storage, distribution and monitoring of convalescent COVID-19 plasma (FDA guidance; EC guidance).
Minimizing the impact on drug manufacturing and supply
An ongoing concern during the pandemic has been the potential impacts on the medical product supply chain, potentially leading to supply disruptions or shortages of drug and biological products. To help prevent or mitigate shortages of such products, the FDA issued guidance to assist manufacturers in providing FDA timely, informative notifications about changes in the production of certain drugs and biological products. Similarly, the EMA quickly began reviewing manufacturing information to identify the medicines most at risk of shortages and disruptions, to prioritize them for remedial actions. EU Member States shared models currently in use to forecast the future demand of crucial medicines, discussed ways to improve their forecasting capacities and looked at best practices regarding data modelling.
To minimize future disruptions to drug manufacturing, companies are reviewing their supply chains to determine if they can be diversified in geography and capacity.
are also starting to review their supply chains for opportunities to diversify in terms of geographic location and capacity, hoping to minimize the impact of a disruption in one area and ensure at least a partial supply.
The pandemic has highlighted potential weaknesses in more than just medication supply—in the entire ecosystem. Governments and regulators have taken this opportunity to review and strengthen processes and procedures to avoid the same ldisruption and public health impact in the case of a future outbreak.
The Pharmaceutical Strategy for Europe includes an agenda of legislative and non-legislative actions for the coming years:
- Revision of the basic pharmaceutical legislation to make it future-proof and innovation friendly
- Proposal for an EU Health Emergency Response Authority
- Structured dialogue with and between all actors in the pharmaceutical manufacturing and public authorities to identify vulnerabilities in the global supply chain and shape policy options to strengthen supply continuity and security
- Improved affordability and cost-effectiveness of medicines and health system’s sustainability;
- Robust digital infrastructure
- Support of research and innovation
- Promotion of innovative approaches to R&D and public procurement for antimicrobials and their alternatives and measures to restrict and optimize their use
To reduce serious cross-border threats to health, the EC also proposed a new framework to strengthen preparedness, reinforce surveillance, improve data reporting of health systems indicators, and stockpile and procure crisis-relevant products.
To help develop resilient health and social care, the EC published an Expert Panel opinion, which reviews the following recommendations:
- Create adaptive surge capacity
- Invest in primary care and mental health
- Disaggregate patient data to ensure equity-driven decision making
- Evaluate strategies to monitor and reduce disinformation
- Link databases across systems and sectors, in line with an integrated whole-of-society approach
- Provide specific training on dealing with socially deprived and minority groups
- Develop a resilience test toolkit and implementation methodology for health systems
Collaboration is key
COVID-19 continues to be a rapidly evolving situation, and regulatory authorities must overcome challenges across the entire health care spectrum. Responses should remain coordinated, rapid and collaborative globally. The pandemic has reminded us that our wellbeing and health outcomes are linked with those of our neighbors and their capacity. We are all in this together.
To stay up to date on regulatory requirements and save time during submissions, visit clarivate.com/cortelliscmc, and continue checking our blog for additional updates and late-breaking news related to COVID-19.
To read the rest of the blog series, visit clarivate.com/cortellis/tag/covid-regulatory-response/.