Drug safety and pharmacovigilance are two faces of a coin

If one were to describe the relationship between drug safety and pharmacovigilance; the most concise way of describing it is by calling them as two sides of the same coin. The aspects of drug safety and pharmacovigilance are intricately and inseparably bound together. The whole purpose of pharmacovigilance is the assurance of drug safety. It is precisely to ensure drug safety, more than anything else, that pharmacovigilance has come into being as a discipline.

Pharmacovigilance (PV in drug industry parlance) is a means to ensuring drug surveillance across the entire process, right from procuring of raw materials to consumption and the effects of consumption. So, pharmacovigilance has to be implemented right across the chain of activities that go into drug manufacturing. It has to ensure compliance with regulation at all stages, namely before the product is manufactured, during the manufacture, and after it enters the market. It is an indispensable aspect of a Quality System, and plays a central role in inspections and audits.

Drug safety and pharmacovigilance are tied together at the level of regulatory bodies. There are different PV rules for different markets. For instance, while the FDA has its own set of PV guidelines; the EU has its own. A clinician or drug company involved in drug safety and pharmacovigilance has to be aware of the regulations in the markets into which the company's products are sold and has to abide by them.

In order to ensure drug safety, pharmacovigilance is carried out by agencies and governments across the globe in accordance with strict guidelines. Drug safety and pharmacovigilance pair together in a number of areas. These are some of them:

Clinical trial:The work of ensuring drug safety through pharmacovigilance starts at the stage of the clinical trial itself. Pharmacovigilance ensures that drug safety is built into the drug right at the clinical trial stage. PV sets out a number of processes and methods by which a pharmaceutical company involved in clinical trials has to go in order to ensure drug safety.

Marketing:PV is set out in the marketing stage of a drug, too. Drug safety brought about by pharmacovigilance is to be implemented at the marketing stage of the drug, including processes for its safe storage, handling and transit. Throughout all these stages, drug safety and pharmacovigilance guidelines are to be strictly implemented.

Governmental drug distribution:Drug safety and pharmacovigilance are also built in by governments in their interactions with each other. For instance, when the government of a country or an agency such as the UN is shipping drugs to another country to support a health program; utmost drug safety is ensured through the principles of pharmacovigilance.

Drug safety and pharmacovigilance in disease management:Several governments across the world, along with international agencies conduct disease control management or emergency handling across the globe, especially in developing countries. Pharmacovigilance is the means to ensure that the drugs administered at these programs are safe for human consumption.

Learn more on this topic by visiting: 

http://bit.ly/Safety-Reporting-in-Clinical-Trials-San-Diego

http://bit.ly/Validation-and-21-CFR-11-Compliance-of-Computer-Systems

http://bit.ly/During-an-Inspection

Orphan Drugs in the USA

Orphan drugs are drugs that are exclusively developed and used for treating rare diseases. Orphan drugs are not researched and developed for widespread use, since by their nature, they are meant only for rare diseases. Since by definition, a rare disease is not likely to have too many patients; orphan drugs are limited in their research, development and eventually, the market.

Situation governing orphan drugs in the USA

Different countries and markets have their own rules for how orphan drugs are developed and marketed. Orphan drugs in the USA have rules designated as to their application. Three major aspects mark out the rules relating to orphan drugs in the USA:

Liberal rules for clinical research

One, there are sufficient leniencies relating to the conduct of the clinical research for the orphan drugs in the USA. The requirement that non- orphan drugs in the USA need to make in relation to sample size does not apply to orphan drugs in the USA. This is natural, considering that fixing a sample size for the clinical research makes no sense, since in many cases, the full number of people suffering from the rare disease, that is, the people for whom the drug is being developed, could be quite nominal. In such instances, it will not be possible for the study to gather a big sample trial size.

Stresses the role of governments

Secondly, research and development of orphan drugs in the USA requires the intervention of the government, not-for-profit organizations that fund such activities, and philanthropy for support. In the case of non-orphan drugs in the USA; there are sufficient incentives for full-scale development and monetization. This is not so in the case of orphan drugs, since as noted, the population needing the drug could be miniscule.

Unencumbered approval process

As an offshoot of these two factors, the FDA has made the approval process of orphan drugs in the USA extremely easy and simple. Again, this is also based on the same logic that governs the entire nature of orphan drugs in the USA: their need in people who do not belong to the general population. To bring about incentives for orphan drugs in the USA; the federal government has passed The Orphan Drug Act.

The Orphan Drug Act

As a means to concretize the role of orphan drugs in the USA; the US administration passed the Orphan Drug Act in 1983. Aimed at encouraging firms to take up development of drugs for products with a very limited market, the Orphan Drug Act has the following features:

• It makes manufacturers of orphan drugs eligible for incentives such as a seven-year exclusivity
• It offers tax rebates of up to half of all their costs spent on research and development, and several other tax incentives for clinical trials of orphan drugs in the USA.

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Investigational New Drug Applications in the USA

Under current Federal law; any manufacturer wanting to market a drug in the US has to subject the drug to an approved marketing application before its transportation and/or distribution in the different States in the US. Since there is a strong possibility that the sponsor of a clinical trial may want to ship the investigational drug to clinical investigators across several states, the sponsor would ideally look to get exempted from this legal requirement. The mechanism through which this exemption issues to the sponsor from the FDA is the Investigational New Drug Applications in the USA.

That is, an Investigational New Drug Application is a request that the sponsor makes with the FDA for authorization to administer a biological product or an investigational drug to humans. This authorization needs to be secured before the product goes through interstate shipment. It also needs to happen before a drug that is not the same as an approved New Drug Application or Biologics/Product License Application is administered.

The logic behind filing Investigational New Drug Application

The entire idea behind filing an Investigational New Drug Application is to ensure the drug's safety for use in humans. This leads to the embarking of steps for its commercialization. The Investigational New Drug Application is often the first step that paves the way for further actions such as data collection to reinforce its safety factor. An Investigational New Drug Application is a sort of guarantee that when the drug that is at this stage of studies is administered on humans; they do not carry risks.

When does the FDA's role begin?

The FDA's role in the Investigational New Drug Application begins at the time when the sponsor wants to test the effect on humans of molecules that is identified earlier.

Types of INDs

There are three types of Investigational New Drug Applications:

What should an Investigational New Drug Application contain?

An Investigational New Drug Application should contain the following:

• Studies done to test animal pharmacology and toxicology
• Information concerning manufacturing
• Information about the Investigational New Drug Application's clinical protocols and investigator

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A word about the Drug Development Process

The heart of all the stages a drug undergoes is the drug development process. Within the drug development process lies a description of each and every step that goes into the development of the drug. The FDA describes five steps that the drug development process has to undergo:

One:The drug's discovery and development

Two:Preclinical research

Three:Clinical research

Four:FDA review

Five:Post Market safety monitoring by the FDA

Stage One:This stage is when the discovery and development that leads to the drug development process of the drug takes place. Innumerable compounds are tested for their ability to get developed into a drug at this stage. Scientists and researchers carry out this stage of the drug development and select a few of these for further study. Protocols of the selected compound are put in place to identify its viability for getting developed into a drug. Core aspects that go into this stage include the manner of its absorption and distribution in the body, side effects, the proper form and dosage, its reaction in varied demographic clusters such as gender, age, race and so on.

Stage Two:In vitro and in vivo tests are carried out at this stage for setting the requirements of the drug for complying with Good Laboratory Practices (GLP) and determining whether it does or not. An important reason for this stage of drug development process is that it offers information on critical aspects such as toxicity of the drug. These results lead scientists to determine if the drug can be, or has to be tested on humans.

Stage Three:Drug development process at this stage is done to decide the precise manner in which the drug needs to be tested on humans, and makes way for the investigational new drug process (IND).

Stage Four:Following the IND process; the drug has to start the New Drug Application (NDA) process. The NDA, which is the complete history of the drug from the earliest stage, opens up the drug for FDA approval. The FDA approval is the final benchmark that the drug needs if it is to be marketed. This is a very lengthy process and, depending on the type of drug, can take years.

Stage Five:Although this is formally the point at which the FDA approves the drug for marketing; the drug development process goes on. The FDA monitors the product much after its entry into the market.

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The FDA's requirements for Drug Applications and Submissions

The FDA's requirements for Drug Applications and Submissions

The FDA has set out requirements by which it accepts drug applications and submissions. It accepts drug applications and submissions through two formats, the New Drug Application (NDA) and Abbreviated New Drug Application (ANDA). The NDA and the ANDA are the mediums through which the FDA eventually approves drug applications and submissions.

The NDA process

The NDA is one the two mechanisms through which the FDA accepts drug applications and submissions. This application is available with the FDA. Any sponsor of a clinical study, be it an organization or an individual, can apply for the NDA and can submit the same, when it is convinced that it has sufficient evidence that its study meets the FDA' requirements for marketing approval.

The way to go about filing for an NDA as part of drug applications and submissions is this:

The ANDA process

The ANDA is the other method of drug applications and submissions to the FDA. Being the counterpart of the NDA; the ANDA is the application a company makes for getting a generic drug approved by the FDA for marketing. The ANDA also has to contain the same data as contained in the NDA drug applications and submissions, but is not required to be accompanied by the data of the clinical research. It is for this reason that they are called by their name.

In place of the clinical research data, the ANDA format of drug applications and submissions has to contain evidence that the product has the ability to perform the same functions of the original drug. This is called the drug's bioequivalent value. Like in the case of the NDA, the ANDA too is allocated a reference number as part of its drug applications and submissions.

Common factors taken into consideration

In either of these methods, the primary considerations for the FDA include the following:

• The safety and effectiveness of the drug
• Its ability to meet its intended use
• Its ability of its benefits to outweigh its risks
• The appropriateness of the drug's planned labeling and its contents
• The ability of the methods used in the manufacturing of the drug to meet Good Manufacturing Practice (GMP)
• The capacity of the drug to have to controls in place for maintaining its quality, purity, strength and identity

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