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How FDA is preparing for wave of change to personalized medicine?
The cost of DNA sequencing is dropping continuously. In very future, majority of the population will have access to their genetic background and they will be able to take it their doctor and will expect to receive personalized treatment rather than a drug that has worked for millions of people but not guaranteed to work for them. Pharmaceutical industry will eventually have to change their business model and transition to personalized medicine. I am wondering how this impacts the regulatory affairs in pharmaceutical industry. How the FDA is preparing itself and evolving to address this trend of change to personalized medicine?
The "one-size-fits-all medicines" description has been used by Mr. Carotenuto as a criticism. There is no need to be so negative; in fact, one-fits-all is perfectly fine for example for antibiotics, as long as physicians are willing to determine what particular organism / bacteria has infected the particular patient.
Somewhat incorrectly termed "personalized medicine" - a better term is "precision medicine" approach does something similar, by first determining the actual cause of disease and then applying appropriate therapy. It is not intended to be tailored to individual patients but simply to a subset of patients that possess the appropriate genetic / other relevant biological background.
I think that FDA will have time to decide in early stages of personalizing medicine, because the main thing that needs adjustment is the quantity of drug a person should take to be effective.
If some existing drug is not effective, the second approach should be changing the drug, combining two drugs or using enhancers.
In the future, and taking on account the evolution of CRISP-like methods and gene therapies, the framework should change to include this as a new genome driven medicine.
Juan Pablo Allocati
Some one from the FDA can no doubt answer this question.
Let's step back and verbalize what we anticipate the "personslized" medicine will actually look like in practice. I anticipate that the main change will be in terms of disease diagnosis, for example based on gene analysis determining what drug would be most effective for an individual patient. No drugs will specifically be made for individual patients. The current Precision Medicine Initiative does not include developing personalized precision drugs, hence the treatment will still use the existing therapies.
First of all we have to define the needs of personalized medicine in specific and only then it can be applied efficiantly.second, it should include building a personal profile of ones needs as for the all taken drugs inpot and address also the interaction infuance between all the drugs input because now it is very much can cause more harm then help if not taking this issue into consideration . - ORIT
The biggest cost of drug development is not in drug discovery and development (this cost being under the control of pharmaceutical companies), but in the clinical-trial phase (the cost of this is driven by clinical investigators and their institutions). Further, an average cost of drug development is high because only few percent of drugs entering development reach the market (due to failure of clinical studies to reach the desired outcomes).
It would be very useful to come up with ideas as to how to implement the "One by one, painfully, there can be quality driven improvements along with efficiencies that ultimately will trim down costs of care" approach could be applied to clinical studies...
I see that my answer is providing a lot of comments, that's great!!! Thanks to Pietro to provide such an input in the personal medecine field. That's good to know at raise a question, how many patients are treated yearly per such specific needs? What are the manufacturers doing to meet that demand? That's the question I raised by telling that such manufacturing demand is not in line with big factories...
This answer is tipical from research specialist who are defenetly looking to discover molecules or treatment which aims to solve specific therapies. Once this has been done, you can't move your product to market simply because it is considered accurate, you have to comply with a bunch of regulatory items which are far from the benchtop studies in order to insure not only the accuracy of the treatment but also the safety of the product and the reproduibility of the manufacturing. Nevertheless, I will be mild in my conisderation and will let you think the way you do. Unfortunately, I have experienced many discovery which have been left at research stage because of this lack of understanding of the regulatory issues to move the product to market.
The Personalized Medicine is just an ongoing practice fro FDA. I'm describing a briefly report to reply to the main question.
In 2016, for the third year in a row, personalized medicines accounted for more than 20 percent of all new
molecular entities (NMEs) approved by the U.S. Food and Drug Administration (FDA). FDA’s Center for Drug
Evaluation and Research (CDER) approved 22 NMEs, new drugs, agents or
therapeutic biologics, in 2016. Of the 22, the Personalized Medicine Coalition (PMC) classified six of them — more
than 25 percent — as personalized medicines, continuing a trend that PMC first documented in 2014 when it pointed out that nine of 41 NMEs approved that year are personalized medicines. The analysis underlines that nearly one of every four drugs the agency approved from 2014 to 2016 is a personalized medicine. That ratio is a sharp increase from 2005, when personalized medicines accounted for just 5 percent of NME approvals. When evaluating NMEs, PMC categorizes personalized medicines as those therapeutic products for which the label includes reference to specific biological markers, identified by diagnostic tools, that help guide decisions and/or procedures for their use in individual patients.
Newly Approved Medicines
The six personalized medicines approved in 2016 include:
- Rubraca (rucaparib) for the treatment of advanced ovarian cancer. The decision to use this product
is informed by the BRCA1/2 biomarker status in patients.
- Exondys 51 (eteplirsen) for the treatment of Duchenne muscular dystrophy. The decision to use
this product is informed by the DMD mutation biomarker status in patients.
- Epclusa (sofosbuvir and velpatasvir) for the treatment of chronic hepatitis C infection. The decision
to use this product is informed by the HCV genotype status of the viral infection in patients.
- Tecentriq (atezolizumab) for the treatment of advanced or metastatic urothelial cancer and
metastatic non-small cell lung cancer. The decision to use this product is informed by PD-L1
expression levels in the tumors of patients.
- Venclexta (venetoclax) for the treatment of chronic lymphocytic leukemia. The decision to use this
product is informed by the chromosome 17p deletion biomarker status in patients.
- Zepatier (elbasvir and grazoprevir) for the treatment of chronic hepatitis C infection. The decision
to use this product is informed by the HCV genotype 1 and 4 biomarker status of the viral infection
Reading this informative comment it occurred to me that the term "personalized medicine" is somewhat of an exageration. To some extent it matches the definition that designation as "personalized" "meets someone's individual requirements".
However, to be more exact, the "personalized" medicines in the current context simply add more definition, specification about what group of patients the drug should be used.
Every FDA-approved drug comes with a package insert that clearly describes its INDICATIONS AND USAGE. Adding to this information more specific description relating to the mode of drug action does not make it "personalized". It simply narrows the size of the population for which the drug may be effective...
Yes, the new era is just started:
THE PHARMACEUTICAL industry makes billions of dollars a year selling one-size-fits-all medicines. But now the race is on to come up with tailor-made drugs that will treat people based on their individual genetic makeup.
Drug companies hope to create a map of genetic landmarks that will become a potent new tool for uncovering the minute inborn differences that make some individuals particularly susceptible to certain diseases. With that knowledge, the drug makers hope to develop safer, more potent drugs that can more precisely target the variety of biological quirks that underlie each major disease. Their goal: a cornucopia of personalized medicines that will produce huge profits into the next century.
Given the politics in Wash DC these days, its confusing with mixed signals as to trend or speed of change. However, the direction for change and easing regulatory burdens is now becoming much clearer. FDA speeding up drug approvals, CMS reducing administrative burdens, and some Executive Orders to-date by Trump clearly support allowing progress to be made while embracing new technologies in a safe manner.
Let me make few points.
Cost of DNA analysis is of little significance in the current care for patients. 1. physician is unlikely to know what the heck the analysis means in relation to the patients condition, and 2. if he does, appropriate specific, "precision" medicines are not yet available.
Further, personalized medicines are unlikely ever to be made to fit individual patients. As it is now, medicines are developed for groups of patients with the same disease and a similar biological / genetic / etc. background.
Two government programs are currently under way - Precision Medicine Initiative to generate new information about the nature / mechanisms / of diseases and life-style effects on disease, and Accelerating Medicines Partnership to generate knew knowledge so that clinical srudies could be designed to fail less often. Neither of these projects aims to develop new drugs; that task is being left to pharmaceutical industry.
Easing regulatory burden will not cut it. We first need more knowledge about diseases and consequently better drugs. Making regulations easier is likely to achieve only one thing - more bad drugs will be made faster!
Good point about continuing bad drugs, however, there are costs associated with everything that is done in research, development, production, marketing and sales. One by one, painfully, there can be quality driven improvements along with efficiencies that ultimately will trim down costs of care.
Perhaps the biggest savings actually comes in contracting with 3rd parties and middleman during marketing phase of the drug.
I'm reporting below a briefly summary of a paper on Nature of April 2015 higliting the "great promise" of the Precision Medicine.
Every day, millions of people are taking medications that will not help them. The top ten highest-grossing drugs in the United States help between 1 in 25 and 1 in 4 of the people who take them (see 'Imprecision medicine'). For some drugs, such as statins — routinely used to lower cholesterol — as few as 1 in 50 may benefit1. There are even drugs that are harmful to certain ethnic groups because of the bias towards white Western participants in classical clinical trials2.
Recognition that physicians need to take individual variability into account is driving huge interest in 'precision' medicine. In January, US President Barack Obama announced a US$215-million national Precision Medicine Initiative. This includes, among other things, the establishment of a national database of the genetic and other data of one million people in the United States. Classical clinical trials harvest a handful of measurements from thousands of people. Precision medicine requires different ways of testing interventions. Researchers need to probe the myriad factors — genetic and environmental, among others — that shape a person's response to a particular treatment.
Studies that focus on a single person — known as N-of-1 trials — will be a crucial part of the mix. Physicians have long done these in an ad hoc way. For instance, a doctor may prescribe one drug for hypertension and monitor its effect on a person's blood pressure before trying a different one. But few clinicians or researchers have formalized this approach into well-designed trials — usually just a handful of measurements are taken, and only during treatment.
If enough data are collected over a sufficiently long time, and appropriate control interventions are used, the trial participant can be confidently identified as a responder or non-responder to a treatment. Aggregated results of many N-of-1 trials (all carried out in the same way) will offer information about how to better treat subsets of the population or even the population at large.
Formalizing and scaling up the N-of-1 approach means solving various practical problems. These include exploiting the diversity of health-monitoring devices, developing new ones and identifying appropriate disease biomarkers, such as tumour DNA circulating in the bloodstream. It will also require a cultural shift on many levels — in regulatory agencies, in pharmaceutical companies and, most of all, in the clinic.
Manufacturers aren't clear in describing what they are doing to meet the demand for personalized medicine. Such new technology demand clearly is not in line with traditional manufacturing and most likely could lead to unique collaborations with hospitals or clinics for joint "manufacturing" of individualized therapies.
The issue of personalized medicine / precision medicine (PM) is not to "...adapt the manufacturing equipment and technology to the needs in order to address such specific demand." In order for PM to work, by the time the general population of patients will have access to information on their genetic background, clinical studies for drug approval will need to be performed with subjects for which genetic backround is fully documented, and drugs will need to be approved only for populations of patients for which the drug has therapeutic efficacy.
All this of course depends on the validity of assumption that genetic background is the only factor that determines drug efficacy. This assumption is unlikely to be true in all cases...
You either did not read my text correctly, or you did not understand it. I WAS CLEARLY TALKING ABOUT APPROVED DRUGS, for which all you talk about (safety, tox, manufacturing validation, etc. and CLINICAL STUDIES have been done to the FDA satisfaction. I am not talking about an R&D but about the whole drug development and approval process. PM - precision medicine - needs to be precise. Such task will include manufacturing but will not be solved by manufacturing. Pharma industry has a long way to go ...