The new pharmacovigilance policy has been introduced intensively, and those who are good at it are protected from falling!

On April 18, CDE's official website released the "Notice on Publicly Soliciting Comments on the Technical Guiding Principles of Drug Clinical Dependence Research (Draft for Comment)" (for details, click "Read the original text " at the bottom of the article )

In fact, in the process of aligning with ICH, China has intensively issued a series of supporting documents on pharmacovigilance

Pharmaco vigilance (PV) was first proposed by French scientists in 1974; in 2002, the World Health Organization further refined the relevant definition, defining pharmacovigilance as the discovery, evaluation, understanding and prevention of adverse drug effects or any other drug-related problems science and activities

In this definition, the adverse drug reactions mentioned are more familiar to everyone, and some people even mistake pharmacovigilance as another term for monitoring adverse drug reactions

Not so

Pharmacovigilance is a comprehensive drug safety supervision system covering the entire life cycle of drugs.

In 2019, the new Drug Administration Law formally proposed the pharmacovigilance system, and Article 12 clarified that “the state shall establish a pharmacovigilance system to monitor, identify, evaluate and control adverse drug reactions and other harmful reactions related to drug use”

A series of policies and regulations issued subsequently accelerated the construction of China's pharmacovigilance-related systems
.

Including the "Measures for the Supervision and Administration of Drug Production" in 2020, which requires that "drug marketing license holders shall establish a pharmacovigilance system"; "Requires that "the sponsor should adjust the clinical trial protocol, suspend or terminate the clinical trial in a timely manner", and also propose that "those who cannot fulfill the responsibility for continuous inspection of drug quality, efficacy and adverse reactions" will not be re-registered
.

In 2021, the State Food and Drug Administration issued the "Quality Management Practice for Pharmacovigilance" (GVP), and this year issued the "Guidelines for Pharmacovigilance Inspection"
.
At this point, pharmacovigilance has a separate quality management specification, as well as supporting inspection guidelines
.

In terms of drug research and development , in the process of aligning with ICH, a series of supporting documents on pharmacovigilance have been intensively issued, such as the "Standards for the Evaluation and Management of Safety Information During Drug Clinical Trials (Trial)", "Standards for the Administration of Safety Update Reports During the Research and Development Period ( Trial Implementation)", "Case Safety Report E2B (R3) Regional Implementation Guidelines",
etc.
This year, CDE first released the "Technical Guidelines for Drug Non-clinical Dependence Research" in January, and now it has begun to solicit opinions on the "Technical Guidelines for Drug Clinical Dependence Research"
.

The key to different "life" with the same drug

As the country pays more and more attention to pharmacovigilance, pharmaceutical companies must also elevate pharmacovigilance to an important position, even a strategic one
.

However, at present, many domestic pharmaceutical companies and consumers seem to have misunderstandings about pharmacovigilance, especially when it comes to adverse drug reactions, they think it is not good, which affects the listing and sales of products
.
Therefore, in the instructions of many medicines, adverse reactions and prohibitions are mentioned in one go, and even "unclear" is written
.

However, the effects of adverse drug reactions are controllable, and pharmacovigilance is not only a "stumbling block" on the way to the market and sales of drugs, but an important "protection"
.

Thalidomide:

When it comes to this drug, everyone's first reaction may be the famous "respiratory arrest event", which is also the beginning of the regulatory authorities' attention to adverse drug reactions
.
However, after the withdrawal of thalidomide from the market, the matter actually has a follow-up
.

First, some doctors found that thalidomide can effectively reduce fever and night sweats in patients, and improve the skin lesions of patients with erythema nodosum leprosy
.
And more than 30 years after the "respiratory arrest event", the FDA again approved the listing of thalidomide for the treatment of erythema nodosum leprosy; 8 years later, an indication for the treatment of multiple myeloma was added
.

Of course, the relaunched thalidomide has a comprehensive program to control prescribing, dispensing, and drug use—the thalidomide prescribing safety education system to ensure that pregnant women are not exposed to thalidomide
.

It is the role and significance of pharmacovigilance to detect and prevent adverse drug reactions and other drug safety problems
.

Merck's rofecoxib and Pfizer's celecoxib:

Both drugs are COX-2 selective inhibitors, and both have similar clinical and market performance
.
However, the former was withdrawn from the market in 2004, that is, five years after its listing due to serious adverse cardiovascular reactions, not only the annual sales of 2.
5 billion US dollars were wiped out, but Merck paid a huge compensation of about 5 billion US dollars; In contrast, celecoxib, which is still popular today
.

There's a key difference between the two -- the label for celecoxib mentions cardiovascular risk
.

"In the beginning, the pharmaceutical company thought that too many adverse reactions were written on the instructions, which would affect the sales after the market
.
But if the warning was not given to the patients, once a similar adverse reaction problem occurred, it would be difficult to escape legal responsibility
.
If the writing clearly informs the possible risks, at least it is not easy to be accused
.
" Dr.
Li Hao, a pharmacovigilance expert, commented on this case
.

New vigilance measures help drug development

Pharmacovigilance runs through the entire life cycle of a drug.
What adverse events will occur in this process with almost no clear observation end point? How likely is it to appear? Under what circumstances will it appear? Which adverse events are drug-related? These are the difficulties and the key points of pharmacovigilance
.

A common approach is to collect, analyze and monitor adverse drug information, and then take countermeasures
.
Of course, this method is more passive, while pharmacovigilance emphasizes actively carrying out various evaluations related to drug safety
.

For example, before the start of clinical research, actively collect all kinds of literature related to the product under study, predict the possible adverse reactions of the product in the future, and follow up directionally
.
Now there are teams that apply big data to pharmacovigilance and help pharmacovigilance through data intelligence technology
.

Adverse reactions can also be warned in advance through biomarkers in the patient's body
.
Some drugs bind to specific biomarkers, causing adverse effects, but these biomarkers may only be present in specific genetic subtype populations
.
If this can be clarified in advance, coupled with gene sequencing of patients, patients with these biomarkers will be excluded in advance to avoid adverse reactions
.

All in all, in the process of drug research and development, the role of pharmacovigilance should be brought into full play, and the risks of drugs should be clarified and prevented before they occur, so as to truly remove the "stumbling blocks" on the road and make drugs more promising
.