FDA Guidance on Covid-19 Vaccine Dosing

FDA Statement on Following the Authorized Dosing Schedules for COVID-19 Vaccines The following statement is attributed to FDA Commissioner Stephen M. Hahn, M.D. and Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research Two different mRNA vaccines have now shown remarkable effectiveness of about 95% in preventing COVID-19 infection in adults. As the first round of vaccine recipients become eligible to receive their second dose, we want to remind the public about the importance of receiving COVID-19 vaccines according to how they’ve been authorized by the FDA in order to safely receive the level of protection observed in the large randomized trials supporting their effectiveness. We have been following the discussions and news reports about reducing the number of doses, extending the length of time between doses, changing the dose (half-dose), or mixing and matching vaccines in order to immunize more people against COVID-19. These are all reasonable questions to consider and evaluate in clinical trials. However, at this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19. The available data continue to support the use of two specified doses of each authorized vaccine at specified intervals. For the Pfizer-BioNTech COVID-19 vaccine, the interval is 21 days between the first and second dose. And for the Moderna COVID-19 vaccine, the interval is 28 days between the first and second dose. What we have seen is that the data in the firms’ submissions regarding the first dose is commonly being misinterpreted. In the phase 3 trials, 98% of participants in the Pfizer-BioNTech trial and 92% of participants in the Moderna trial received two doses of the vaccine at either a three- or four-week interval, respectively. Those participants who did not receive two vaccine doses at either a three-or four-week interval were generally only followed for a short period of time, such that we cannot conclude anything definitive about the depth or duration of protection after a single dose of vaccine from the single dose percentages reported by the companies.  Using a single dose regimen and/or administering less than the dose studied in the clinical trials without understanding the nature of the depth and duration of protection that it provides is concerning, as there is some indication that the depth of the immune response is associated with the duration of protection provided. If people do not truly know how protective a vaccine is, there is the potential for harm because they may assume that they are fully protected when they are not, and accordingly, alter their behavior to take unnecessary risks. We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster. However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health. We have committed time and time again to make decisions based on data and science. Until vaccine manufacturers have data and science supporting a change, we continue to strongly recommend that health care providers follow the FDA-authorized dosing schedule for each COVID-19 vaccine. The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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Disturbing Discovery by FDA that Chocolate often has undeclared Milk

Since I have a son with food allergies, I was appalled by this story that FDA has determined that chocolate often has undeclared milk. Click the link below to the full story for more information.

What FDA Learned About Dark Chocolate and Milk Allergies

Note: This Consumer Update sheds further light on the results of an FDA study on milk in dark chocolate shared in an earlier story. For more detail, read the study results.

If you’re allergic to milk and you love dark chocolate, how do you know whether you can indulge in a candy bar without having an allergic reaction? That’s what the Food and Drug Administration (FDA) wanted to learn, especially after receiving reports that consumers had harmful reactions after eating dark chocolate.

~TJK

FDA FY 2010 Inspectional Observation Summaries

The FDA has recently updated their published  483 inspection results here. This is really a great resource as it breaks the findings down by regulation and how often it was cited. The link is to the 2010 483 that I stumbled upon. The parent site has multiple years and in sortable formats:

http://www.fda.gov/ICECI/Inspections/ucm250720.htm

~TJK

 

21 CFR part 11 Update

Folks, it looks like some of our US regulations and guidance documents have been flagged for update by FDA….including everyone’s favorite, 21 CFR part 11 (source Cerulean’s email newsletter). I don’t anticipate major changes, just clarification on their intent.  Everyone enjoy your Friday.

New Guidance Agenda for 2009 Released by FDA

The FDA’s CDER has published its list of expected guidance documents and revised regulations to be issued this year (2009).

Readers of our 2009 forecast will find many items on the list familiar:

· 21 CFR Part 11

· Process Validation

· Adaptive Clinical Trial Design

· Contract manufacturing

· Various marketing, promotional and labeling guidance

· “Dear Healthcare Professional Letters” for recalls

TJK

Ignorance on the Placebo Effect

I was reading some blog posts over at Wellsphere when I saw the following thoughts on the placebo effect from Seth Roberts

What Should Double-Blind Placebo-Controlled Trials Be Replaced With?

For a sick person, which is worse?

1. Getting better for the wrong reason.

2. Wasting a lot of money.

It sounds like a joke — #1 isn’t even harmful, whereas the cost of health care is a very serious problem. Yet the FDA and legislators with FDA oversight have been given this choice — and chosen #1. They have chosen to protect us against #1 but not #2.

If you get better from a placebo effect, that’s the wrong reason. How dare you! The requirement that drugs be better than placebo controls prevents this from happening. The requirement might have been — but isn’t — that a new drug be better than pre-existing alternatives. Many aren’t but they are always more expensive — not to mention more risky.

Now Seth has a Ph.D. in psychology, blogs on science-related topics, and seems like a smart enough guy, but his post is a bit misguided.

1) The reason that drugs are required to perform better than a placebo is because the placebo effect tends to only occur in a small set of patients. That is that the mental makeup of a specific patient is the cause of a placebo response (irregardless of the treatment). It is also not clear whether a placebo respondee is “actually getting better”. It is just as likely that they were not actually sick in the first place (or as sick as they thought).

2) Those patients who are not predisposed toward exhibiting placebo responses need to be given an actual effective treatment to “get better” and therefore deserve medications that exhibit “better than placebo” characteristics. Giving such a sick patient a sham treatment (rather than one that can actually work) can be very harmful in that the person’s condition can actually worsen.

3) There is a requirement from FDA (and regulatory agencies worldwide) that new drugs be as good or better than existing medications; or that they provide some sort of unique benefit (or reduced risk).

4) The expense of new medications is largely due to the high cost of research to make those medications (and fund future research). The low-hanging fruit is largely gone.

Best,

TJK

Roles for QA

I was scanning through my email subscriptions today and noted an interesting item in my FDA News Drug Daily Bulletin (from the company “FDA News”) advertising one of their publications. Now, most of the time these “industry best practice” white papers are information that is common-sensical or freely available from another source (e.g., compilations of FDA Warning Letters that are available on the www.fda.gov website) so I typically ignore them. However, the tone and posturing of this one caught my eye:

 

Lower Your Site Risk Potential (SRP) Score
Lower Your Site Risk Potential (SRP) Score zeroes in on what this risk-ranking model is and how FDA is using it to classify manufacturing plants and prioritize enforcement. This new management report also goes a vital extra step, showing you how to implement practical strategies that can reduce your score, limit inspections and unlock a host of valuable new business benefits.
To order, go to http://www.fdanews.com/store/product/detail?productId=23141.

 

To me, that is marketing to the worst of us. It doesn’t offer help to actually improve one’s processes, systems, or products so as to have more successful inspections. It implies that by doing certain things, a manufacturer can place themselves “below FDA’s radar” and thereby reduce the number of inspections to which one is subject. That is not to say that the advertisement is selling a lousy or unethical document. I wouldn’t know since I haven’t read it.

The ad did get me thinking about the various roles I play as a QA Auditor though. I was born an optimist, but through my work in QA, I’ve become somewhat of a reluctant realist. There are always those who will seek out “the quick and easy path” rather than the high road. That being said, my role varies depending upon with what I’m dealing:

 

1) In my opinion, most people I meet and with whom I’ve worked are genuinely interested in doing a good job, the right thing, etc.; and for that I am thankful. And as a QA professional, my primary job is to help them do just that. By serving as a fresh pair of eyes, as an uninvolved outsider, I can help those who may be by necessity focused on the trees, see the forest. This is the role I like best, that of an internal consultant.

 

2) In other instances, there are those who are very ready to make what a former mentor of mine liked to call “overly pragmatic decisions”. For situations like this, my role tends to be more akin to that of a traffic cop. Almost everybody slows down when they see a parked patrol car. My presence lets people know that “someone is looking”.

 

3) In the worst cases, I’m there to catch the most aggregious offenders, those who totally disregard ethical or moral considerations; or who are just so sloppy in their practice that they pose a major risk to their subjects, the public, or the research itself. I play the role of the enforcer in these cases. I like this role the least. However, I try to remember that it is because of this minority situation that there will always be a role for Quality Assurance.

 

~TJK