Webinar notes: Revision of EU pharmaceutical legislation

Today, I listened to a webinar, "Even spaceships need a launchpad" presented by Reuters that focused on the ongoing revision of EU pharmaceutical legislation. That legislation is currently 20 years old.

 

There were for 4 panelists:

Emer Cooke, EMA

Nathalie Molle, EFPIA

Florian Schmidt, European Commission

Cristian-Silviu Busoi, European Parliament

 

The background to the discussion was that the EU has been falling behind in several fronts related to bringing new therapies to patients compared to other countries, including:

• Regulations do not support well the newer therapies (e.g., cell and gene therapies)
• Newer therapies include device combinations (~25%) that require bridging communications with the agency responsible for devices (delivery and companion diagnostics) and the two different regulatory frameworks
• A question remains is EMA staffed adequately to deal with the current science and the volume of work
• Fewer expedited pathways
• Practices need to be harmonized more across the countries

 

Once therapies are approved by the EU (EMA), taking on average 466 days, each of the 27 member countries has to approve. Subsequent to the individual country approvals, is the actual process (i.e., access) for getting new therapies to patients that include the payer approvals.

 

Emer Cooke refocused the discussion getting new therapies to patients.  She noted that a focus on unmet medical need therapies could be a more impactful approach vs therapies that provide only minor improvements over existing therapies. Additionally, an ongoing approach for multi-national review teams is aimed improving the post-EU approvals with the country approvals.

 

Florian Schmidt wants to improve the communications between the pharmaceutical sponsors and regulators to ensure more guidance is provided during the therapy development.  In the end, making sure that right research is completed so that the final submission is can undergo a smooth review.  He also wants to change the regulations to bring the drug and device regulators together to meet with the pharmaceutical sponsors during development so that the sponsors understand the expectations and have guidance from the regulators.

 

Overall, it was an interesting and insightful discussion on the challenges for obtaining new therapy approvals in the EU. Collaboration amongst the pharmaceutical therapy ecosystem is central to the future success. Worthwhile hearing for those who are supporting new therapy approvals for the EU.

American Society for Mass Spectrometry Course is Offering 15 Short Courses of Interest to Bioanalysts and Biomarker Scientists

ASMS will be offering the Two-Day Short Courses, Saturday and Sunday, June 3 and 4, 2023

 

All of the following two-day short courses will be in-person only at the George R. Brown (GRB) Convention Center in Houston, TX.  Several short courses will now be offered ONLINE, asynchronous to the annual conference.

 

Course offerings:

01 Bioinformatics for Protein Identification

 

02 Clinical Biomarkers: Development and Validation

03 DMPK: Experimentation and Data Interpretation

04 Glycans and Glycoproteins in Mass Spectrometry

05 LC-MS: Practical Maintenance and Troubleshooting

06 LC-MS/MS: Practical Method Development (Saturday one-day course)
            AND Bioanalytical Method Validation (Sunday one-day course)

07 LC-MS/MS: Understanding, Optimizing and Applying Techniques using Electrospray, APCI and APPI                 to Develop Successful Methods for Qualitative and Quantitative Analysis

08 Machine Learning for Mass Spectrometry Data Analysis

09 Native Mass Spectrometry

10 Peptides and Proteins in Mass Spectrometry

 

11 Protein Therapeutics: Practical Characterization and Quantitation by Mass Spectrometry

12 Quantitative Mass Spectrometry

 

13 Quantitative Proteomics: Case Studies

 

14 R for Mass Spectrometry Data Analysis: Getting Started

15 Top-Down Proteomics (Saturday one-day course) 

        AND Top-Down MS Data Analysis and Visualization (Sunday one-day course)

Article: Researchers predict Alzheimer's progression 3.5 years early with unique blood test

Published in Brain, "Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum"

There is a long way to go before this cell-based is able to be used widely in assessing the general population, but further exploration of the factors that are affecting the hippocampal progenitors may produce a more simplified assay. My congratulations to the researchers who are furthering our understanding of this complex disease. 

 

Abstract:

Adult hippocampal neurogenesis is important for learning and memory and is altered early in Alzheimer’s disease. As hippocampal neurogenesis is modulated by the circulatory systemic environment, evaluating a proxy of how hippocampal neurogenesis is affected by the systemic milieu could serve as an early biomarker for Alzheimer’s disease progression. Here, we used an in vitroassay to model the impact of systemic environment on hippocampal neurogenesis. A human hippocampal progenitor cell line was treated with longitudinal serum samples from individuals with mild cognitive impairment, who either progressed to Alzheimer’s disease or remained cognitively stable. Mild cognitive impairment to Alzheimer’s disease progression was characterized most prominently with decreased proliferation, increased cell death and increased neurogenesis. A subset of ‘baseline’ cellular readouts together with education level were able to predict Alzheimer’s disease progression. The assay could provide a powerful platform for early prognosis, monitoring disease progression and further mechanistic studies.

Article: AI has designed bacteria-killing proteins from scratch – and they work

Unfortunately, the article is behind a pay wall, but what is visible is tantalizing:

An AI was tasked with creating proteins with anti-microbial properties. Researchers then created a subset of the proteins and found some did the job

An AI has designed anti-microbial proteins that were then tested in real life and shown to work. The same approach could eventually be used to make new medicines.

Proteins are made of chains of amino acids. The sequence of those acids determine the protein’s shape and function.

Ali Madani at Profluent, a biotechnology start-up in California, and his colleagues used an AI to design millions of new proteins, then created a small sample of those to test whether they worked.

The potential to use AI to target proteins and pathways in bacterial disease may keep us apace of the changes that nature builds continues to build into bacteria, and may ultimately produce new antibiotics. It will be interesting to see whom the company partners with to screen these compounds for safety and efficacy before entering animal and human trials.
 

 

First oral selective estrogen receptor degrader (SERD) approved by FDA

 From the article:

Italian drugmaker Menarini has succeeded where three European Big Pharmas have failed, pushing the first oral selective estrogen receptor degrader (SERD) to treat breast cancer across the FDA finish line.

The agency has signed off on Orserdu (elacestrant) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

 AZ released an injectable SERD in 2002, and Roche, AZ and Sanofi had failed trials of their oral SERD.  The approval for Menarini also comes with an approval for a companion diagnostic. 

In an age where biologics, gene and cell therapies are growing, it is nice to see that oral drugs are still achieving approvals.  The companion diagnostic also shows the continued value of targeting the right patients to achieve success and not treat patient who will not respond.

Publication: Commutability assessment of human urine certified reference materials for albumin and creatinine on multiple clinical analyzers using different statistical models

 I first heard about "communtability" from Russ Grant (Labcorp) at either a CPSA or AAPS Crystal City conference during discussions of biomarkers.  The discussion furthered my enlightenment on the practices in clinical laboratories that support medical practice. These practices, while in some cases similar to the FDA Bioanalytical Method Validation guidance, are different; as would be expected for the differences in intended use of the data. John Allinson (Immunologix Laboratories), Steve Piccoli (SPARC) and Erica Troksa (Labcorp) subsequently challenged my notions on the application of BMV to biomarkers measured in clinical laboratories and helped me realize that clinical laboratory practices are many times superior to bioanalytical labs when it comes to measuring biomarkers; especially when considering the intended use of the data.

In this case, the authors of the article explore albumin and creatinine reference materials tested across several clinical analyzers to assess the comparability/comparability of the devices and their assays for these analytes (measurands) in urine.  There are numerous publications that discuss the challenges in achieving comparable (note not equivalent) results across clinical laboratories. This article explores one lab-based approach and 2 statistical approaches to demonstrate that the data from the different instruments and assays are similar enough to result in a common outcome (i.e., medical determination):

Abstract

Urine albumin concentration and albumin–creatinine ratio are important for the screening of early-stage kidney damage. Commutable urine certified reference materials (CRMs) for albumin and creatinine are necessary for standardization of urine albumin and accurate measurement of albumin–urine ratio. Two urine CRMs for albumin and creatinine with certified values determined using higher-order reference measurement procedures were evaluated for their commutability on five brands/models of clinical analyzers where different reagent kits were used, including Roche Cobas c702, Roche Cobas c311, Siemens Atellica CH, Beckman Coulter AU5800, and Abbott Architect c16000. The commutability study was conducted by measuring at least 26 authentic patient urine samples and the human urine CRMs using both reference measurement procedures and the routine methods. Both the linear regression model suggested by the Clinical and Laboratory Standard Institute (CLSI) guidelines and log-transformed model recommended by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Commutability Working Group were used to evaluate the commutability of the human urine CRMs. The commutability of the human urine CRMs was found to be generally satisfactory on all five clinical analyzers for both albumin and creatinine, suggesting that they are suitable to be used routinely by clinical laboratories as quality control or for method validation of urine albumin and creatinine measurements. [Analytical and Bioanalytical Chemistry volume 415, pages 787–800 (2023)]

AI writing bots - what are your thoughts on their use in writing sceintific research articles?

The Verge published an article on "ChatGPT can’t be credited as an author, says world’s largest academic publisher":

“Springer Nature, the world’s largest academic publisher, has clarified its policies on the use of AI writing tools in scientific papers. The company announced this week that software like ChatGPT can’t be credited as an author in papers published in its thousands of journals. However, Springer says it has no problem with scientists using AI to help write or generate ideas for research, as long as this contribution is properly disclosed by the authors.”

 

Interesting points from the article are raised about the quality of some of the writing:

"If there is broad consensus on crediting AI as an author, though, there is less clarity on the use of AI tools to write a paper, even with proper acknowledgment. This is in part due to well-documented problems with the output of these tools. AI writing software can amplify social biases like sexism and racism and has a tendency to produce “plausible bullshit” — incorrect information presented as fact."

The recent explosion of these AI tools for writing and their apparent use already in the peer-reviewed literature was a bit of a surprise to me.  It took many years for me to improve my writing skills, and I've worked with many people to improve their skills. Good clear writing, especially scientific writing, is a mixture of knowing punctuation, grammar, vocabulary, and planning; not to mention practice. Reading well-written articles is also helpful in improving one's skills. Clarity and brevity have long been my problem - they need to be balanced to get the message across to the reader without making them read long-winded tomes.

 

Having peer-reviewed 100's of articles, I've seen the spectrum of writing - from good to bad, and have been surprised at what can slip through the publishing company's editors and made it into print.  The allure of the AI is understandable to achieve a better written outcome, but as the article notes - may frequently generate "plausible bullshit" - something we need to keep out of scientific articles.

So what is your view on using AI; whether it is for e-mails or scientific publications?

FDA Center for Devices and Radiological Health releases 2022 Annual Report

 

You may wonder why I would post about CDRH activities. Since they are involved in approving devices and assays/tests for clinical laboratories (i.e., biomarker tests), they play an important part in delivering medical care to patients.

 

 From the announcement:

The FDA’s Center for Devices and Radiological Health (CDRH) released its 2022 Annual Report to highlight the Center’s programmatic accomplishments through December 31, 2022, including the Pandemic Response, the Medical Device User Fee Amendment (MDUFA) V, Device Innovation, Over-the-Counter (OTC) Hearing Aid Final Rule, and Device Safety.

 

Topics covered in the report include:

• CDRH By the Numbers
• Pandemic Response
• COVID-19
• Mpox
• MDUFA V
• Device Innovation
• Novel Devices
• Upstream Innovation
• Expediting Premarket Submissions
• Marketing Authorizations for Novel Devices
• Digital Health
• OTC Hearing Aid Final Rule
• Device Safety
• Recalls
• Cybersecurity
• Material Safety
• Health of Women Strategic Plan
• Real World Evidence / Real World Data

Article: CRISPR technology one step closer to approval in a new therapy

EMA validates Vertex's CRISPR application, clearing barrier on road to landmark approval

FierceBiotech published an article yesterday noting:

“The candidate, exagamglogene autotemcel (exa-cel), is an autologous cell therapy treatment for sickle cell disease and transfusion-dependent beta thalassemia. By using CRISPR-Cas9 to edit a patient’s own hematopoietic stem cells, the partners modify cells to produce high levels of fetal hemoglobin. One-time treatment with exa-cel has freed patients from transfusions and vaso-occlusive crises.

…

Exa-cel, formerly known as CTX001, has PRIME designation from the EMA, making it eligible for a priority review that usually takes 150 days, rather than the typical 210 days. The timeline suggests exa-cel could win approval in Europe later this year and become the first marketed CRISPR-Cas9_treatment."

Article: New Report: More than 160 medicines in development for mental illness

PhRMA released a report and a list of new therapies under development for mental illnesses.  The article notes:

• 54 for depression, which affects 8.4% of adults and 17% of adolescents aged 12 to 17 in the U.S.
• 35 for schizophrenia, which affects less than 1% of U.S. adults.
• 35 for anxiety disorders. More than a third of adults in the U.S. report experiencing anxiety during their lifetime.
• 33 for substance use disorders. Over 40 million Americans ages 12 and older—or 14.5% of the U.S. population—reported having a substance use disorder in 2020.
• 13 for bipolar disorder which affects about 2.8% of adults and 2.9% of adolescents in the U.S.
• 8 for attention-deficit/hyperactivity disorder (ADHD) which is one the most common childhood disorders with a lifetime prevalence of 11.0% in children ages four to 17 and 8.7% in adolescents ages 13 to 18. ADHD also affects 4.4% of adults in the U.S.
  

The report can be accessed here and the list of new therapies here.

Welcome

In past positions, sharing information to staff and collaborators that was of interest or essential to their success was a daily priority for me. I look to continue that practice with this blog.  I'll post a variety of information, including:

- science related to developing new therapeutics

- updates on bioanalytical news

- updates on biomarkers and diseases

- regulatory news (new draft and final regulations, workshops, webinars) covering GLP, GCP, CLIA, and IVDR

-  interesting topics 

I plan to post a few times a week and look forward to hearing your comments on the post topics. Please follow me to receive notification of new posts.