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The Phentermine Story - Pharmacist Review

From: Ron Males
Series: Popular Drugs in America
Length: 04:01

Phentermine's journey from its introduction in 1959 to its utilization in the present day has seen various ups and downs. Despite challenges and controversies, phentermine remains a valuable tool in weight loss management when used under the guidance of healthcare professionals. Phentermine has a long history of conflicts with FDA too, In the drug development and approval process, the drug manufacturer assumes responsibility for testing a new drug's safety and effectiveness. This involves conducting pre-clinical research, including animal testing, followed by three phases of clinical trials involving human subjects.

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When the FDA approves a drug, it signifies that they have determined the benefits of the drug to outweigh the risks when it becomes available to the general population. During the testing phase of a drug, around 3,000 individuals participate in the final stage of clinical trials. However, if a serious side effect occurs in, for example, one out of 10,000 people, the manufacturer and the FDA may not become aware of it until the drug is already on the market and hundreds of thousands or even millions of people have taken it.

I believe it is important for Americans to understand that every time they consume a pill, especially a new one they have never taken before, it's essentially an experiment. These drugs go on the market with only about 3,000 patients ever having used them. We will never know all the potential toxicity that can occur, particularly the rare cases of one in 10,000 or one in 20,000 individuals who may be seriously harmed. Our ability to detect such cases only happens after the drug has been exposed to a significant number of patients.

Who is responsible for drug safety within the FDA?

The FDA's Center for Drug Evaluation and Research (CDER) is the branch responsible for overseeing drug safety and regulation. With a staff of approximately 1,800 individuals, CDER reviews drug applications submitted by pharmaceutical companies, monitors drugs once they are on the market, and keeps the public informed through updates. Currently, Steven Galson is serving as the acting director of CDER, while Paul Seligman is the acting director of CDER's Office of Drug Safety.

Where does the FDA receive funding for drug safety?

Under the Prescription Drug User Fee Act, CDER collects fees from drug manufacturers to support the drug approval process. The fee amount is determined by law and adjusted annually to account for inflation. As reported in a financial report for Fiscal Year 2002, the FDA collected fees totaling $143.3 million. CDER's total operating cost for reviewing drugs during that year was $209.8 million.

What is considered an "adverse event," and how common are they?

The FDA defines an "adverse event," commonly known as a "side effect," as any negative experience associated with the use of a medical product in a patient. An adverse event should be reported if it results in death, disability, hospitalization, poses a life-threatening situation, causes a congenital anomaly, or requires treatment to prevent permanent damage. According to Paul Seligman, director of the Office of Drug Safety in CDER, the FDA receives approximately 278,000 reports of adverse events each year, with 30,000 of them classified as serious. Drug-related adverse events account for an estimated 100,000 deaths annually. More than a dozen drugs have been withdrawn since 1997.

Why is drug phentermine controversial ?

The drug Phentermine has generated controversy due to several reasons. Here are a few factors contributing to its controversial nature:

  1. Side Effects: Phentermine is a stimulant and appetite suppressant that affects the central nervous system. It can lead to various side effects, including increased heart rate, elevated blood pressure, insomnia, dry mouth, irritability, and potential dependence or addiction. These side effects can be concerning, particularly for individuals with underlying health conditions or those prone to substance abuse.

  2. Short-Term Use: Phentermine is typically prescribed for short-term use, usually up to 12 weeks, due to its potential for dependence and tolerance. Extended use can result in reduced effectiveness and an increased risk of adverse effects.

  3. Controlled Substance: Phentermine is classified as a controlled substance in many countries, including the United States. It is regulated due to its potential for abuse and addiction, which limits its availability and requires a prescription from a healthcare professional.

The controversies surrounding Phentermine have led to an increased interest in natural alternatives. People seeking weight loss solutions may prefer natural alternatives due to the following reasons:

  1. Safety: Natural alternatives are often perceived as safer since they are derived from natural ingredients and are typically not associated with the same level of side effects and risks as pharmaceutical drugs.

  2. Long-Term Use: Natural alternatives may offer the advantage of long-term use without the concerns of dependence or reduced effectiveness over time. They are often seen as a sustainable solution for maintaining weight loss goals.

  3. Holistic Approach: Natural alternatives tend to promote a holistic approach to weight loss, focusing on lifestyle modifications, including diet and exercise, in addition to supplement support. This comprehensive approach is appealing to individuals seeking overall well-being and sustainable weight management.


How does Phentermine work?

Phentermine is a medication commonly prescribed for short-term weight loss treatment. Its mechanism of action involves appetite suppression, increased energy expenditure, activation of the sympathetic nervous system, and stimulation of dopamine release. These effects collectively contribute to reduced calorie intake, enhanced metabolism, and improved focus on weight loss goals.

It's important to note that Phentermine should only be used under the guidance of a healthcare professional, and its use is typically recommended for a limited duration due to potential side effects and the risk of dependence. If you are considering Phentermine or any weight loss medication, consult with a healthcare provider to determine if it is suitable for your individual circumstances and to ensure its safe and effective use.

It is classified as a sympathomimetic amine and acts as an appetite suppressant. More insights into its mechanism of action and the effects it has on the body-

How Does Phentermine Work?

Phentermine primarily works by targeting the central nervous system (CNS) to reduce hunger cravings and increase feelings of fullness. Here's a breakdown of its key mechanisms:

  1. Appetite Suppression: Phentermine stimulates the release of norepinephrine, a neurotransmitter that affects hunger signals in the brain. By increasing norepinephrine levels, Phentermine helps suppress appetite and reduce food cravings.

  2. Increased Energy Expenditure: Phentermine also activates the release of adrenaline, which leads to an increase in energy expenditure. This effect can enhance metabolism and promote calorie burning, aiding in weight loss efforts.

  3. Sympathetic Nervous System Stimulation: As a sympathomimetic amine, Phentermine activates the sympathetic nervous system, which regulates various bodily functions. This activation can result in increased heart rate and blood pressure, leading to heightened alertness and energy levels.

  4. Dopamine Release: Phentermine additionally stimulates the release of dopamine, a neurotransmitter associated with reward and motivation. This effect may help individuals stay motivated and focused on their weight loss goals.

Links to Relevant Sources:

  1. Phentermine Overview - Mayo Clinic
  2. How Does Phentermine Work? - Medical News Today
  3. Phentermine Mechanism of Action - PubMed
  4. Sympathetic Nervous System - National Institute of General Medical Sciences
  5. Dopamine and Motivation - Psychology Today
  6. Outlook article on Generic phen alternatives

How does the FDA become aware of adverse events?

Typically, doctors and healthcare professionals report adverse events to the drug companies, who are then legally obligated to forward serious reports to the FDA within 15 days. For the first three years after a drug's approval, the manufacturer must also provide quarterly reports of all adverse event information to the FDA, followed by annual reports after three years.

The FDA also maintains a voluntary system called Medwatch, where consumers and healthcare professionals can directly report adverse events to the Office of Drug Safety. The FDA receives around 1,000 such reports per day, handled by a team of approximately 50 staff members. These reports are then directed to evaluators with the relevant expertise, who may reach out to the reporter for additional information.

Since adverse event reporting is voluntary, it becomes challenging for the FDA to accurately determine the number of injuries or deaths associated with a specific drug. Obtaining these figures requires a Freedom of Information Act request for the adverse event records pertaining to the particular drug.

What actions does the FDA take upon learning about a drug's adverse effects?

The FDA's response to adverse effects varies based on the severity of the side effects and the significance of the drug for the treated condition, considering the availability of alternative treatments in the market. The FDA may implement risk management strategies, such as modifying the drug's labeling to include a "black box" warning. Additionally, the FDA may issue a "Dear Doctor" letter to healthcare professionals, providing them with information about the identified additional risks associated with the drug. These matters are discussed with the drug manufacturer, and an advisory committee may be convened to seek external opinions on the appropriate course of action.

How does the FDA determine if a drug should be withdrawn from the market?

If it becomes evident that the risks of a drug outweigh its benefits, and prior warnings have not sufficiently mitigated the danger to the public, a drug company may voluntarily withdraw the drug or comply with the FDA's request for its withdrawal from the market. Furthermore, the FDA possesses the authority, as mandated by law, to enforce a mandatory recall of the drug. Since 1997, more than a dozen drugs have been withdrawn from the market.

History of Phentermine with FDA

Phentermine, a drug widely recognized for its role in medically managed weight loss plans, has a fascinating history in the pharmaceutical industry. Since its initial introduction in 1959, physicians have relied on phentermine to help reduce the appetite of their obese patients and promote calorie reduction. Despite its efficacy, phentermine has faced certain challenges throughout its history, resulting in its classification as a controlled substance in most countries. So, what is the story behind phentermine and how is it utilized today?

First Available in 1959:

In the late 1950s, phentermine made its debut in the market. The U.S. Food and Drug Administration granted approval for the use of phentermine resin as a treatment for obesity. This drug was considered a safer alternative to the "Rainbow pills" that were previously employed—an amalgamation of amphetamine, thyroid hormone, digitalis, and diuretics—which often led to severe complications.

Weight Loss Trends of the 1970s:

During the 1970s, phentermine gained prominence when combined with two other FDA-approved drugs. One such combination was the popular cocktail known as Fen-Phen, which consisted of phentermine along with fenfluramine, a serotonin-releasing agent. Although the FDA did not officially approve the mixture of these drugs, doctors prescribed them together for weight loss patients. In 1996 alone, approximately 6.6 million prescriptions were written for the Fen-Phen cocktail.

Another combination, known as Dexfen-Phen, paired phentermine with dexfenfluramine to manage obesity. Dexfenfluramine, approved by the FDA in 1996, also reduced appetite. When combined with phentermine, patients experienced reduced food intake while maintaining high energy levels. However, both drug cocktails lost popularity swiftly due to health concerns associated with the combination of different medications.

In 1997, scientists at the Mayo Clinic discovered a link between the use of the Fen-Phen cocktail and heart valve disease. Further connections were made between fenfluramine, dexfenfluramine, and heart valve complications. In fact, their research revealed that 30 percent of evaluated patients had taken one of these drugs in combination with phentermine. Consequently, in July of 1997, the FDA issued an advisory reporting the relationship between the Fen-Phen cocktail and heart valve disease. The Mayo Clinic published their findings in the New England Journal of Medicine shortly thereafter. As a result, the FDA requested pharmaceutical companies to voluntarily remove fenfluramine and dexfenfluramine from the market. However, phentermine remained available for use.

The Introduction of Phen-Pro:

In present times, physicians have a new weight loss combination to offer, known as Phen-Pro. This regimen involves pairing an antidepressant such as Prozac, Zoloft, or Effexor with phentermine. The antidepressant allows the benefits of phentermine to last longer since the effect tends to diminish when taken alone. Although the FDA has not officially approved the combined use of these drugs, there is no evidence suggesting that they cause the health problems associated with previous "phen" cocktails.

The Popularity of Phentermine and Imitations:

The popularity of phentermine as an appetite suppressant has led to the emergence of several imitations, many of which turn out to be scams. Nonetheless, there are a few non-prescription formulas similar to phentermine available in the market that boost metabolism and increase energy levels.

Phentermine's journey from its introduction in 1959 to its utilization in the present day has seen various ups and downs. Despite challenges and controversies, phentermine remains a valuable tool in weight loss management when used under the guidance of healthcare professionals.

In the realm of weight loss, physicians now have a new option to consider—a weight loss cocktail that combines an antidepressant such as Prozac, Zoloft, or Effexor with phentermine. The inclusion of an antidepressant enhances the longevity of the benefits derived from taking phentermine. When used alone, the effects of phentermine tend to diminish relatively quickly, resulting in a shorter duration of effectiveness. Although the FDA has not granted approval for the combined use of these drugs, there is currently no evidence to suggest that their combination leads to the health problems associated with previous "phen" cocktails.

The popularity of phentermine as an appetite suppressant has given rise to numerous imitations, although caution is advised as many of these alternatives are fraudulent scams. Nevertheless, a few non-prescription formulas similar to phentermine are available on the market, designed to boost metabolism and increase energy levels.

 

What role does the FDA play in the drug development and approval process?

In the drug development and approval process, the drug manufacturer assumes responsibility for testing a new drug's safety and effectiveness. This involves conducting pre-clinical research, including animal testing, followed by three phases of clinical trials involving human subjects. The gathered data is compiled into a "new drug application" (NDA), which is submitted to the FDA for review.

The filed NDA undergoes evaluation by the FDA's Center for Drug Evaluation and Research (CDER). FDA scientists, including doctors, statisticians, microbiologists, pharmacologists, and chemists, review the evidence presented by the drug company. They assess the drug's efficacy, safety, and whether the benefits outweigh any risks. If additional information is required, the CDER may consult with the drug company or seek input from external experts through the formation of an advisory committee. After evaluating the labeling information and assessing the manufacturer's facility quality, the application enters the "NDA action" phase, where the division director reviews the CDER evaluation and makes the final decision.

Piece Description

When the FDA approves a drug, it signifies that they have determined the benefits of the drug to outweigh the risks when it becomes available to the general population. During the testing phase of a drug, around 3,000 individuals participate in the final stage of clinical trials. However, if a serious side effect occurs in, for example, one out of 10,000 people, the manufacturer and the FDA may not become aware of it until the drug is already on the market and hundreds of thousands or even millions of people have taken it.

I believe it is important for Americans to understand that every time they consume a pill, especially a new one they have never taken before, it's essentially an experiment. These drugs go on the market with only about 3,000 patients ever having used them. We will never know all the potential toxicity that can occur, particularly the rare cases of one in 10,000 or one in 20,000 individuals who may be seriously harmed. Our ability to detect such cases only happens after the drug has been exposed to a significant number of patients.

Who is responsible for drug safety within the FDA?

The FDA's Center for Drug Evaluation and Research (CDER) is the branch responsible for overseeing drug safety and regulation. With a staff of approximately 1,800 individuals, CDER reviews drug applications submitted by pharmaceutical companies, monitors drugs once they are on the market, and keeps the public informed through updates. Currently, Steven Galson is serving as the acting director of CDER, while Paul Seligman is the acting director of CDER's Office of Drug Safety.

Where does the FDA receive funding for drug safety?

Under the Prescription Drug User Fee Act, CDER collects fees from drug manufacturers to support the drug approval process. The fee amount is determined by law and adjusted annually to account for inflation. As reported in a financial report for Fiscal Year 2002, the FDA collected fees totaling $143.3 million. CDER's total operating cost for reviewing drugs during that year was $209.8 million.

What is considered an "adverse event," and how common are they?

The FDA defines an "adverse event," commonly known as a "side effect," as any negative experience associated with the use of a medical product in a patient. An adverse event should be reported if it results in death, disability, hospitalization, poses a life-threatening situation, causes a congenital anomaly, or requires treatment to prevent permanent damage. According to Paul Seligman, director of the Office of Drug Safety in CDER, the FDA receives approximately 278,000 reports of adverse events each year, with 30,000 of them classified as serious. Drug-related adverse events account for an estimated 100,000 deaths annually. More than a dozen drugs have been withdrawn since 1997.

Why is drug phentermine controversial ?

The drug Phentermine has generated controversy due to several reasons. Here are a few factors contributing to its controversial nature:

  1. Side Effects: Phentermine is a stimulant and appetite suppressant that affects the central nervous system. It can lead to various side effects, including increased heart rate, elevated blood pressure, insomnia, dry mouth, irritability, and potential dependence or addiction. These side effects can be concerning, particularly for individuals with underlying health conditions or those prone to substance abuse.

  2. Short-Term Use: Phentermine is typically prescribed for short-term use, usually up to 12 weeks, due to its potential for dependence and tolerance. Extended use can result in reduced effectiveness and an increased risk of adverse effects.

  3. Controlled Substance: Phentermine is classified as a controlled substance in many countries, including the United States. It is regulated due to its potential for abuse and addiction, which limits its availability and requires a prescription from a healthcare professional.

The controversies surrounding Phentermine have led to an increased interest in natural alternatives. People seeking weight loss solutions may prefer natural alternatives due to the following reasons:

  1. Safety: Natural alternatives are often perceived as safer since they are derived from natural ingredients and are typically not associated with the same level of side effects and risks as pharmaceutical drugs.

  2. Long-Term Use: Natural alternatives may offer the advantage of long-term use without the concerns of dependence or reduced effectiveness over time. They are often seen as a sustainable solution for maintaining weight loss goals.

  3. Holistic Approach: Natural alternatives tend to promote a holistic approach to weight loss, focusing on lifestyle modifications, including diet and exercise, in addition to supplement support. This comprehensive approach is appealing to individuals seeking overall well-being and sustainable weight management.


How does Phentermine work?

Phentermine is a medication commonly prescribed for short-term weight loss treatment. Its mechanism of action involves appetite suppression, increased energy expenditure, activation of the sympathetic nervous system, and stimulation of dopamine release. These effects collectively contribute to reduced calorie intake, enhanced metabolism, and improved focus on weight loss goals.

It's important to note that Phentermine should only be used under the guidance of a healthcare professional, and its use is typically recommended for a limited duration due to potential side effects and the risk of dependence. If you are considering Phentermine or any weight loss medication, consult with a healthcare provider to determine if it is suitable for your individual circumstances and to ensure its safe and effective use.

It is classified as a sympathomimetic amine and acts as an appetite suppressant. More insights into its mechanism of action and the effects it has on the body-

How Does Phentermine Work?

Phentermine primarily works by targeting the central nervous system (CNS) to reduce hunger cravings and increase feelings of fullness. Here's a breakdown of its key mechanisms:

  1. Appetite Suppression: Phentermine stimulates the release of norepinephrine, a neurotransmitter that affects hunger signals in the brain. By increasing norepinephrine levels, Phentermine helps suppress appetite and reduce food cravings.

  2. Increased Energy Expenditure: Phentermine also activates the release of adrenaline, which leads to an increase in energy expenditure. This effect can enhance metabolism and promote calorie burning, aiding in weight loss efforts.

  3. Sympathetic Nervous System Stimulation: As a sympathomimetic amine, Phentermine activates the sympathetic nervous system, which regulates various bodily functions. This activation can result in increased heart rate and blood pressure, leading to heightened alertness and energy levels.

  4. Dopamine Release: Phentermine additionally stimulates the release of dopamine, a neurotransmitter associated with reward and motivation. This effect may help individuals stay motivated and focused on their weight loss goals.

Links to Relevant Sources:

  1. Phentermine Overview - Mayo Clinic
  2. How Does Phentermine Work? - Medical News Today
  3. Phentermine Mechanism of Action - PubMed
  4. Sympathetic Nervous System - National Institute of General Medical Sciences
  5. Dopamine and Motivation - Psychology Today
  6. Outlook article on Generic phen alternatives

How does the FDA become aware of adverse events?

Typically, doctors and healthcare professionals report adverse events to the drug companies, who are then legally obligated to forward serious reports to the FDA within 15 days. For the first three years after a drug's approval, the manufacturer must also provide quarterly reports of all adverse event information to the FDA, followed by annual reports after three years.

The FDA also maintains a voluntary system called Medwatch, where consumers and healthcare professionals can directly report adverse events to the Office of Drug Safety. The FDA receives around 1,000 such reports per day, handled by a team of approximately 50 staff members. These reports are then directed to evaluators with the relevant expertise, who may reach out to the reporter for additional information.

Since adverse event reporting is voluntary, it becomes challenging for the FDA to accurately determine the number of injuries or deaths associated with a specific drug. Obtaining these figures requires a Freedom of Information Act request for the adverse event records pertaining to the particular drug.

What actions does the FDA take upon learning about a drug's adverse effects?

The FDA's response to adverse effects varies based on the severity of the side effects and the significance of the drug for the treated condition, considering the availability of alternative treatments in the market. The FDA may implement risk management strategies, such as modifying the drug's labeling to include a "black box" warning. Additionally, the FDA may issue a "Dear Doctor" letter to healthcare professionals, providing them with information about the identified additional risks associated with the drug. These matters are discussed with the drug manufacturer, and an advisory committee may be convened to seek external opinions on the appropriate course of action.

How does the FDA determine if a drug should be withdrawn from the market?

If it becomes evident that the risks of a drug outweigh its benefits, and prior warnings have not sufficiently mitigated the danger to the public, a drug company may voluntarily withdraw the drug or comply with the FDA's request for its withdrawal from the market. Furthermore, the FDA possesses the authority, as mandated by law, to enforce a mandatory recall of the drug. Since 1997, more than a dozen drugs have been withdrawn from the market.

History of Phentermine with FDA

Phentermine, a drug widely recognized for its role in medically managed weight loss plans, has a fascinating history in the pharmaceutical industry. Since its initial introduction in 1959, physicians have relied on phentermine to help reduce the appetite of their obese patients and promote calorie reduction. Despite its efficacy, phentermine has faced certain challenges throughout its history, resulting in its classification as a controlled substance in most countries. So, what is the story behind phentermine and how is it utilized today?

First Available in 1959:

In the late 1950s, phentermine made its debut in the market. The U.S. Food and Drug Administration granted approval for the use of phentermine resin as a treatment for obesity. This drug was considered a safer alternative to the "Rainbow pills" that were previously employed—an amalgamation of amphetamine, thyroid hormone, digitalis, and diuretics—which often led to severe complications.

Weight Loss Trends of the 1970s:

During the 1970s, phentermine gained prominence when combined with two other FDA-approved drugs. One such combination was the popular cocktail known as Fen-Phen, which consisted of phentermine along with fenfluramine, a serotonin-releasing agent. Although the FDA did not officially approve the mixture of these drugs, doctors prescribed them together for weight loss patients. In 1996 alone, approximately 6.6 million prescriptions were written for the Fen-Phen cocktail.

Another combination, known as Dexfen-Phen, paired phentermine with dexfenfluramine to manage obesity. Dexfenfluramine, approved by the FDA in 1996, also reduced appetite. When combined with phentermine, patients experienced reduced food intake while maintaining high energy levels. However, both drug cocktails lost popularity swiftly due to health concerns associated with the combination of different medications.

In 1997, scientists at the Mayo Clinic discovered a link between the use of the Fen-Phen cocktail and heart valve disease. Further connections were made between fenfluramine, dexfenfluramine, and heart valve complications. In fact, their research revealed that 30 percent of evaluated patients had taken one of these drugs in combination with phentermine. Consequently, in July of 1997, the FDA issued an advisory reporting the relationship between the Fen-Phen cocktail and heart valve disease. The Mayo Clinic published their findings in the New England Journal of Medicine shortly thereafter. As a result, the FDA requested pharmaceutical companies to voluntarily remove fenfluramine and dexfenfluramine from the market. However, phentermine remained available for use.

The Introduction of Phen-Pro:

In present times, physicians have a new weight loss combination to offer, known as Phen-Pro. This regimen involves pairing an antidepressant such as Prozac, Zoloft, or Effexor with phentermine. The antidepressant allows the benefits of phentermine to last longer since the effect tends to diminish when taken alone. Although the FDA has not officially approved the combined use of these drugs, there is no evidence suggesting that they cause the health problems associated with previous "phen" cocktails.

The Popularity of Phentermine and Imitations:

The popularity of phentermine as an appetite suppressant has led to the emergence of several imitations, many of which turn out to be scams. Nonetheless, there are a few non-prescription formulas similar to phentermine available in the market that boost metabolism and increase energy levels.

Phentermine's journey from its introduction in 1959 to its utilization in the present day has seen various ups and downs. Despite challenges and controversies, phentermine remains a valuable tool in weight loss management when used under the guidance of healthcare professionals.

In the realm of weight loss, physicians now have a new option to consider—a weight loss cocktail that combines an antidepressant such as Prozac, Zoloft, or Effexor with phentermine. The inclusion of an antidepressant enhances the longevity of the benefits derived from taking phentermine. When used alone, the effects of phentermine tend to diminish relatively quickly, resulting in a shorter duration of effectiveness. Although the FDA has not granted approval for the combined use of these drugs, there is currently no evidence to suggest that their combination leads to the health problems associated with previous "phen" cocktails.

The popularity of phentermine as an appetite suppressant has given rise to numerous imitations, although caution is advised as many of these alternatives are fraudulent scams. Nevertheless, a few non-prescription formulas similar to phentermine are available on the market, designed to boost metabolism and increase energy levels.

 

What role does the FDA play in the drug development and approval process?

In the drug development and approval process, the drug manufacturer assumes responsibility for testing a new drug's safety and effectiveness. This involves conducting pre-clinical research, including animal testing, followed by three phases of clinical trials involving human subjects. The gathered data is compiled into a "new drug application" (NDA), which is submitted to the FDA for review.

The filed NDA undergoes evaluation by the FDA's Center for Drug Evaluation and Research (CDER). FDA scientists, including doctors, statisticians, microbiologists, pharmacologists, and chemists, review the evidence presented by the drug company. They assess the drug's efficacy, safety, and whether the benefits outweigh any risks. If additional information is required, the CDER may consult with the drug company or seek input from external experts through the formation of an advisory committee. After evaluating the labeling information and assessing the manufacturer's facility quality, the application enters the "NDA action" phase, where the division director reviews the CDER evaluation and makes the final decision.