Great advances have been made in the knowledge of development and regulatory approval of medicinal product containing genetically modified cells. Although a guideline has been available in the EU since 2012, the current updated version provides a useful guide to developers and professionals involved in the regulatory process of these medicines. This article presents the main issues communicated in that guidance, the regulators\' insights and a commentary from the academic developers\' point of view.

The establishment of core indicators for assessment plays an important role in carrying out the lifecycle value assessment of Chinese patent medicine, which are developed based on the concepts such as clinical value oriented, paying attention to the human use experience, and whole process quality control. To this end, the Specialty Committee of Data Monitoring and Decision Making of the World Federation of Chinese Medicine Societies organized experts to draft the Expert Consensus on Core Indicators for Lifecycle Value Assessment of Chinese Patent Medicine based on the research including Chinese Medicine Registration Review Evidence System in Combination of Traditional Chinese Medicine Theory, Human Use Experience, and Clinical Trials(GZY-FJS-2022-206) by National Administration of Traditional Chinese Medicine. This consensus proposed 92 core indicators from four stages, including new drug R&D project approval, pre-clinical research, new drug marketing authorization, and post-marketing, combining the assessment purposes and needs of different stakeholders from different dimensions such as clinical needs, clinical positioning, human use experience, effectiveness, safety, quality control, innovation, accessibility, and suitability. This consensus also interpreted the indicators to clearly elucidate the core elements of the value assessment of Chinese patent medicine in different R&D stages and guided the stakeholders to identify, analyze, and assess the value of Chinese patent medicine in the R&D and use process based on the core indicators in a scientific, objective, and standardized approach. This consensus is expected to play an important role in the high-quality new drug development, drug pricing and compensation of Chinese patent medicine, the development of clinical pathways, and rational clinical application.

In the European Union, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) develop guidelines to guide drug development, supporting development of efficacious and safe medicines. A European Public Assessment Report (EPAR) is published for every medicine application that has been granted or refused marketing authorisation within the EU. In this work, we study the use of text embeddings and similarity metrics to investigate the semantic similarity between EPARs and EMA guidelines. All 1024 EPARs for initial marketing authorisations from 2008 to 2022 was compared to the 669 current EMA scientific guidelines. Documents were converted to plain text and split into overlapping chunks, generating 265,757 EPAR and 27,649 guideline text chunks. Using a Sentence BERT language model, the chunks were transformed into embeddings and fed into an in-house piecewise matching algorithm to estimate the full-document semantic distance. In an analysis of the document distance scores and product characteristics using a linear regression model, EPARs of anti-virals for systemic use (ATC code J05) and antihemorrhagic medicines (B02) present with statistically significant lower overall semantic distance to guidelines compared to other therapeutic areas, also when adjusting for product age and EPAR length. In conclusion, we believe our approach provides meaningful insight into the interplay between EMA scientific guidelines and the assessment made during regulatory review, and could potentially be used to answer more specific questions such as which therapeutic areas could benefit from additional regulatory guidance.

UNASSIGNED: Many cancer drugs are approved under the US Food and Drug Administration (FDA) accelerated approval pathway based on preliminary evidence. It is unclear how this limited evidence is integrated into the National Comprehensive Cancer Network (NCCN) guidelines, which are common references for clinicians and are used by public and private payers to determine reimbursement for oncology treatments.
UNASSIGNED: To analyze the NCCN guidelines\' assessments for cancer drug indications that received FDA accelerated approval compared with cancer drug indications that received FDA regular approval.
UNASSIGNED: This cross-sectional study analyzes FDA-approved indications for cancer drugs that were granted accelerated approval from program inception in 1992 to June 30, 2022. For each drug, the FDA-approved labeling was reviewed to identify all indications. All analyses were performed at the drug-indication level.
UNASSIGNED: The exposure was FDA regulatory status as of October 2022, including regular approval, accelerated approval, accelerated approval converted to regular approval, and withdrawn accelerated approval.
UNASSIGNED: The level of evidence and consensus (category 1, 2A, 2B, and 3) and treatment preference (preferred, alternative preferred, other recommended, and useful in certain circumstances) ratings assigned by NCCN committees as of February 2023.
UNASSIGNED: A total of 315 oncology indications for 100 drugs were analyzed. These indications included 156 (50%) with regular approval, 60 (38%) with accelerated approval, 78 (49%) with accelerated approval that was converted to regular approval, and 21 (13%) with withdrawn accelerated approvals. Among all indications, 105 (33%) were rated by the NCCN as having category 1 evidence, 185 (59%) with category 2A, 6 (2%) with category 2B, and 2 (1%) with category 3 evidence. Compared with indications with regular approval, those with accelerated approval were less frequently assigned category 1 evidence (47% vs 3%; P < .001) and were less often listed as preferred treatment options (58% vs 40%; P = .008). Among the 21 withdrawn accelerated approval indications, 8 (38%) remained in the NCCN guidelines, with most having level 2A evidence ratings.
UNASSIGNED: This study found that cancer drug indications with accelerated approval were less likely to be assigned high-level evidence ratings and preferred status in the NCCN guidelines compared with indications with regular approval; most accelerated and regular approval drugs had low-quality evidence ratings but high levels of consensus among oncologists on NCCN committees. Greater clarity on the thresholds and definitions of evidence levels would make the NCCN guidelines more useful to clinicians, patients, and payers.

The World Health Assembly resolution on access to biotherapeutics in 2014 urges WHO and Member States to facilitate access to biotherapeutics while ensuring their quality, safety, and efficacy. While efforts to date have contributed to increased availability and better access to biotherapeutics, including biosimilars, huge gaps still remain, with lack of product access identified as a problem in many countries. A thorough review of the WHO guidelines on biosimilars issued in 2009 in view of technical developments, accumulated and emerging scientific evidence as well as experience in biosimilar evaluation since the release of the guidelines provided an opportunity to introduce greater flexibility and to reduce regulatory requirements in biosimilar development where possible. Based on the identification, draft revisions of the WHO guidelines were prepared with input from extensive consultation with various stakeholders and the broader public. The move toward a greater emphasis on quality and functional in vitro assessment enables the reduction of cost and timelines of development and supports streamlined regulatory approval as a first critical step toward product availability. This article includes the key updates that have been incorporated in the revised guidelines but are not restricted to these alone and should be read in conjunction with the guidelines.

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey. Consensus statements were developed based on the findings of a published, peer-reviewed systematic review. Participants evaluated statements in two survey rounds, following the Delphi method. The expert panel achieved consensus on 7 of 21 recommendations regarding the use of randomized clinical trials. The endorsed recommendations were: (i) Results from placebo-controlled trials are the most reliable and (ii) are necessary despite the growing placebo-effect; (iii) it is ethical to enroll patients in placebo-arms when established treatment is available, if there is no evidence of increased health risk; (iv) There is a need to approve new drugs with the same efficacy as existing treatments, but with different side-effect profiles; (v) Non-inferiority trials incur an increased risk of approving ineffective medications; (vi) The risk of approving an ineffective drug justifies trial designs that incur higher costs, and (vii) superiority trials incur the risk of rejecting potentially efficacious treatments. The endorsed recommendations inform the choice of trial-design appropriate for approval of psychopharmacological drugs. The recommendations strongly support the use of randomized clinical trials in general, and the use of placebo-controlled trials in particular.

OBJECTIVE: Molnupiravir is a newer oral antiviral drug that has recently received emergency use authorization (EUA) in USA, UK and India. We aim to conduct an update on our previous systematic review to provide practical clinical guideline for using molnupiravir in patients with COVID-19.
METHODS: We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar until January 5, 2022, using key MeSH keywords.
RESULTS: Final result of phase 3 study in 1433 non-hospitalized COVID-19 patients showed a significant reduction in composite risk of hospital admission or death (absolute risk difference, -3.0% [95% confidence interval {CI}, -5.9 to -0.1%]; 1-sided P = 0.02) although with a non-significant 31% relative risk reduction (RRR). RRR for death alone was 89% (95% CI, 14 to 99; P-value not reported). Number needed to treat to prevent 1 death or 1 hospitalization or death composite appears to be closely competitive to other agents having EUA in people with COVID-19. However, cost-wise molnupiravir is comparatively cheaper compared to all other agents.
CONCLUSIONS: Molnupiravir could be a useful agent in non-pregnant unvaccinated adults with COVID-19 who are at increased risk of severity including hospitalization. However, it is effective only when used within 5-days of onset of symptoms. A 5-days course seems to be safe without any obvious short-term side effects.

OBJECTIVE: It is unknown whether and to what degree trials submitted to the US FDA to support drug approval adhere to NCCN guideline-recommended care in their baseline and surveillance CNS imaging protocols.
OBJECTIVE: We sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging.
METHODS: Retrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling).
METHODS: Estimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging.
RESULTS: A total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations.
CONCLUSIONS: The trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.