Drug Development and Approval Process: From FDA

URL:

"http://www.fda.gov/Drugs/DevelopmentApprovalProcess/default.htm"

Here is the introduction and a few summaries:

Development & Approval Process (Drugs)

American consumers benefit from having access to the safest and most advanced pharmaceutical system in the world.

The main consumer watchdog in this system is the U.S. Food and Drug Administration's Center for Drug Evaluation and Research (CDER). The center's best-known job is to evaluate new drugs before they can be sold. The center's evaluation not only prevents quackery, but also provides doctors and patients the information they need to use medicines wisely. CDER ensures that drugs, both brand-name and generic, work correctly and that their health benefits outweigh their known risks.

Drug companies seeking to sell a drug in the United States must first test it. The company then sends CDER the evidence from these tests to prove the drug is safe and effective for its intended use. A team of CDER physicians, statisticians, chemists, pharmacologists, and other scientists reviews the company's data and proposed labeling. If this independent and unbiased review establishes that a drug's health benefits outweigh its known risks, the drug is approved for sale. The center doesn't actually test drugs itself, although it does conduct limited research in the areas of drug quality, safety, and effectiveness standards.

Before a drug can be tested in people, the drug company or sponsor performs laboratory and animal tests to discover how the drug works and whether it's likely to be safe and work well in humans. Next, a series of tests in people is begun to determine whether the drug is safe when used to treat a disease and whether it provides a real health benefit.

Guidance Documents for Drug Applications

Guidance documents represent the Agency's current thinking on a particular subject. These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products.   They also establish policies intended to achieve consistency in the Agency's regulatory approach and establish inspection and enforcement procedures.  Because guidances are not regulations or laws, they are not enforceable, either through administrative actions or through the courts.  An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.

For the complete list of CDER guidances, please see the Guidance Index.

• The Investigational New Drug Application Process web page has an updated list of all guidances to help in the preparation of IND applications.

Guidance Document for Emergency INDs

• The Guidance for Institutional Review Boards and Clinical Investigators contains information on: Obtaining an Emergency IND, Emergency Exemption from Prospective IRB, Approval Exception From Informed Consent, and Requirement Planned Emergency Research, Informed Consent Exception.

• The New Drug Application Process web page has an updated list of all guidances to help in the preparation of NDA applications.

• The Abbreviated New Drug Application Process web page has an updated list of all guidances to help in the preparation of ANDA applications.

   

Laws, Regulations, Policies and Procedures for Drug Applications

The mission of  FDA is to enforce laws enacted by the U.S. Congress and regulations established by the Agency to protect the consumer's health, safety, and pocketbook.  The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S. With numerous amendments it is the most extensive law of its kind in the world.  The law is intended to assure the consumer that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.

Code of Federal Regulations for Investigational New Drugs (INDs), New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs)

The following  sections provide regulations for INDs and NDAs.  All parts of section 21 of the Code of Federal Regulations are also available.

• CFR Sections for INDs

• CFR Sections for NDAs

• CFR Sections for ANDAs

Manual of Policies and Procedures ().

The following MaPPs provide official instructions for internal practices and procedures followed by CDER staff to help standardize the IND and NDA review process. All CDER MaPPs are available from the MaPP Index webpage.

How Drugs are Developed and Approved

The Center for Drug Evaluation and Research's (CDER) job is to ensure that drugs are safe and effective. CDER does not test drugs, although the Center's Office of Testing and Research does conduct limited research in the areas of drug quality, safety, and effectiveness.

CDER is the largest of FDA's five centers.   It has responsibility for both prescription and over-the-counter drugs. For more information on CDER activities, including performance for drug reviews,  post-marketing risk assessment, and other highlights, please see the CDER Update: Improving Public Health Through Human Drugs The other four FDA centers have responsibility for medical and radiological devices, food, and cosmetics, biologics, and veterinary drugs.

It is the responsibility of the company seeking to market a drug to test it and submit evidence that it is safe and effective. A team of CDER physicians, statisticians, chemists, pharmacologists, and other scientists reviews the sponsor's new drug application (NDA) containing the data and proposed labeling.

The section below entitled From Fish to Pharmacies: The Story of a Drug's Development, illustrates how a drug sponsor can work with FDA's regulations and guidance information to bring a new drug to market.

Development

Osteoporosis, a crippling disease marked by a wasting away of bone mass, affects as many as 2 million American, 80 percent of them women, at an expense of $13.8 billion a year, according to the National Osteoporosis Foundation.,  The disease may be responsible for 5 million fractures of the hip, wrist and spine in people over 50, the foundation says, and may cause 50,000 deaths. Given the pervasiveness of osteoporosis and its cost to society, experts say it is crucial to have therapy alternatives if, for example, a patient can't tolerate estrogen, the first-line treatment.

Enter the salmon, which, like humans, produces a hormone called calcitonin that helps regulate calcium and decreases bone loss.  For osteoporosis patients, taking salmon calcitonin, which is 30 times more potent than that secreted by the human thyroid gland, inhibits the activity of specialized bone cells called osteoclasts that absorb bone tissue.  This enables bone to retain more bone mass.

Though the calcitonin in drugs is based chemically on salmon calcitonin, it is now made synthetically in the lab in a form that copies the molecular structure of the fish gland extract.  Synthetic calcitonin offers a simpler, more economical way to create large quantities of the product.

FDA approved the first drug based on salmon calcitonin in an injectable. Since then, two more drugs, one injectable and one administered through a nasal spray were approved.  An oral version of salmon calcitonin is in clinical trials now.  Salmon calcitonin is approved only for postmenopausal women who cannot tolerate estrogen, or for whom estrogen is not an option.

How did the developers of injectable salmon calcitonin journey "from fish to pharmacies?"

After obtaining promising data from laboratory studies, the salmon calcitonin drug developers took the next step and submitted an Investigational New Drug (IND) application to CDER.  The IND Web page explains the need for this application, the kind of information the application should include, and the Federal regulations to follow.

Once the IND application is in effect, the drug sponsor of salmon calcitonin could begin their clinical trials.  After a sponsor submits an IND application, it must wait 30 days before starting a clinical trial to allow FDA time to review the prospective study.  If FDA finds a problem, it can order a  "clinical hold" to delay an investigation, or interrupt a clinical trial if problems occur during the study.

Clinical trials are experiments that use human subjects to see whether a drug is effective, and what side effects it may cause.  The Running Clinical Trials Webpage provides links to the regulations and guidelines that the clinical investigators of salmon calcitonin must have used to conduct a successful study, and to protect their human subjects.

The salmon calcitonin drug sponsor analyzed the clinical trials data and concluded that enough evidence existed on the drug's safety and effectiveness to meet FDA's requirements for marketing approval.  The sponsor submitted a New Drug Application (NDA) with full information on manufacturing specifications, stability and bioavailablility data, method of analysis of each of the dosage forms the sponsor intends to market, packaging and labeling for both physician and consumer, and the results of any additional toxicological studies not already submitted in the Investigational New Drug application.  The NDA Web page provides resources and guidance on preparing the NDA application, and what to expect during the review process.

New drugs, like other new products, are frequently under patent protection during development. The patent protects the salmon calcitonin sponsor's investment in the drug's development by giving them the sole right to sell the drug while the patent is in effect.   When the patents or other periods of exclusivity on brand-name drugs expire, manufacturers can apply to the FDA to sell generic versions. The Abbreviated New Drug Applications (ANDA) for Generic Drug Products Webpage provides  links to guidances, laws, regulations, policies and procedures, plus other resources to assist in preparing and submitting applications.

Drug sponsors from small businesses can take advantage of special offices and programs designed to help meet their unique needs. The Small Business Assistance Webpage provides links to FDA laws, regulations and guidances that affect small business. Information is also provided on financial assistance and incentives that are available for drug development.

In addition to My Gather Network: Quidnunc Simcha, I am a Guest-Editor and "Conversation Starter" at Conversations for a Better World, Chris Harding, which is a shared blog on population, gender and health, and provided by United Nations Population Fund Website.

Your Gather

Conversations for a Better World

You should consider contribution to Conversations for a Better World as well! The more diverse the discussions the better the results in most instances. Although time to a solution will increase significantly, the final result is usually better for humanity.

You are NOT ALONE!

• Some Information about: Wikileaks and "What is a Whistleblower"?

I love my country, but we have a problem. Spoiled Americans will kill for sport and bullying is an example. Another term for bullying is "gang stalking", which may be more appropriate, but the legal term may be the defined term of "bullying". Some corporate employees and "friends of organizations" use harassment, "bullying or stalking", and believe it is not that bad, but, in truth, it is considered emotional torture-adults and children should refrain. If an adult "bullies", a child will follow their example.

As many know, a Multi-national Study by World Health Organization (1) reports that abused women and men believe "emotional abuse" is worse than physical abuse because it causes life-long psychological trauma and is virtually impossible to prove. The inability to "prove" is why many "pillars" will engage. In fact, corrupt societies are breeding grounds for such activity.

With that said, I would like to add the following links to all of my posts. I hope others will copy and paste the same into their posts as well. The best way to end corruption is to discuss corruption. At the root of most criminal enterprises are corrupt police, citizens, and politicians. The latter are grandmas, grandpas, fathers, mothers, police, church deacons, etc. Be warned, the corrupt people in your environment could begin harassing you.

References:

STOP SEX Trafficking! and Meth!

Support Senator Ron Wyden in his fight against sex-trafficking. Although the Pacific Northwest is the worse US location, it is an American problem and probably associated with the Meth network. Tell me corrupt police do not know about this activity.

Corruption Resources

Buscaglia, Edgardo, & van Dijk, Jan. (2005). UC Berkley: Berkley Program in Law and Economics. Controlling Organized Crime and Corruption in the Public Sector. University of California eScholarship[online]. Jan 2005. Available from: eScholarship. University of California About the New eScholarship

Oregon

Schwartz, Susan P. State of Oregon Criminal Justice Commission. Lane County Criminal Justice Report. Oregon.gov[online]. May 2009. Available from: Report. Oregon Criminal Justice Commission.

Indiana

Long, Billy; Yerington, Courtney. Police Administrators in Indiana: A Descriptive Study of Attitudes, Perceptions, and Stressors. Internet Journal of Criminology[online]. 2006. Available from: Internet Journal of Criminology: Article.

Bullying, Harassment, and Gang Stalking Resources

Bochenek, Michael; Brown, Widney, A.; Breen, Melanie; Campbell, Rook; David, Sam; Henkle, Derek R.; Jesrani, Tejal; Lnzertti,Rachel; McArthur, Kerry; Rozario, Shalu; Zea, Sadie. Hatred in the Hallways, Violence and Discrmination Against Lesbian, Gay, Bsexual, and Transgender Students in U.S. Schools. Human Rights Watch [online].2001. Available from: HRW, Article Database.

Can sarcasm be a form of bullying? These documents say yes if sarcasm is included in a certain contextual relationship to other activity. 
• http://family.samhsa.gov/teach/middleschool_bullies.aspx?printid=1
• http://attorneygeneral.delaware.gov/schools/bullypack.pdf
• http://www.cde.ca.gov/ls/ss/se/documents/bullyingatschool.pdf

Cook, Dane. bullying. Dane Cook's Youtube Channel. 2010. Available from: Youtube

Suicide Resources

National Suicide Prevention Lifeline. Are you in a crisis? Please call 1-800-273-8255 (TALK). Suicide Prevention.

Suicide Awareness Voices Education. SAVE "Doctors, Firefighters and Others SAVE Lives, You Can Too!"

The Trevor Project is a great example of "realizing" the need to remind ourselves of the beauty around us! The World is beautiful! That blade of grass is amazing! The butterfly is magical! If needed, take a walk! If you cannot walk, visit Trevor! In my experiences, Pandora Internet Radio is a life savior as well.

itgetsbetterproject.com,
• "For too long, LGBT youth have been forced to struggle through their formative years suffering from bullies in their schools, churches and homes — and with no support system to provide them any help."
• "Justin Aeberg. Billy Lucas. Cody Barker. Asher Brown. Seth Walsh. Raymond Chase. Tyler Clementi. All the names of American teenagers who in recent months have taken their own lives after being bullied in school."

“As a nation we’re founded on the belief that all of us are equal and each of us deserves the freedom to pursue our own version of happiness; to make the most of our talents; to speak our minds; to not fit in; most of all, to be true to ourselves. That’s the freedom that enriches all of us. That’s what America is all about. And every day, it gets better.”
– President Obama in a video message for the nationwide campaign focused on young people who are being bullied because of their actual or perceived sexual orientation. Video Resources: http://wh.gov/3nn.

Department of Defense. Restoring Hope, You Can Help Save A Life. Restoring Hope. "More Focus Needed to End Suicides", Mullens.

Wise, Terry L. Waking Up: Climbing Through the Darkness. Available from: Amazon.

Wise, Terry. terrywise.com. A National Mental Health Award Winner. Available from: Terry Wise.

Harding, Chris. Suicide: What is your keyword? Gather.com [online]. Available from: Chris Harding's Gather Network.

Dumais, A., B.Sc.; Lesage, A.D., M.D, M.Phil.; Alda, M., M.D; Rouleau, G., M.D., PhD; Dumont, M., R.N.; Chawky, N., M.Ps.; Roy, M., M.D; Mann, J.J., M.D; Benekelfat, C. M.D; Turecki, Gustavo, Turecki, M.D., PhD. Risk Factors for Suicide Completion in Major Depression: A Case-Control Study of Impulsive and Aggressive Behaviors in Men. The American Journal of Psychiatry [online]. 2005, vol.162(11) pp. 2116-2124. Avialable from: Am. J Psychiatry. doi: 10.1176/appi.ajp.162.11.2116.

 

Goldsmith, SK; Pellmar, TC; Kleinman, AM; Bunney, WE; Editors. Committeee on Pathophysiology and Prevention of Adolescent and Adult Suicide Reducing Suicide, A National Imperative. National Academies Press[online]. 2002. pp. xvi, 512. Available from: National Academies Press. ISBN-10: 0-309-08321-4. ISBN-13: 978-0-309-08321-8.

Abuse

1. World Health Organization, Department of Gender and Women's Health. WHO Multi-country Study on Women's Health and Domestic Violence against Women: summary report of initial results on prevalence, health outcomes and women's responses.(Bangladesh, Brazil, Ethiopia, Japan, Namibia, Peru, Samoa, Serbia and Montenegro, Thailand, and United Republic of Tanzania). WHOLIS. 2005. Available from: WHOLIS. ISBN: 9241593512.

Rape and Sexual Assault: Rape and sexual assault,WHO 1997

Wong Fo Lo, Sylvie; Wester, Fred; Mol, Saskia; Romkens, Renee; Hezemans, Door; Lagro-Janssen, Toine. Talking matters: Abused women's views on disclosure of partner abuse to the family doctor and its role in handling the abuse situation. Patient Educ and Couns. 2008, vol.70(3), pp.386-394. Available from: Author's personal copy ISSN 0738-3991

Office of the US Global AIDS Coordinator. The President's Emergency Plan for AIDS Relief Report on Gender-Based Violence and HIV/AIDS. PEPFAR[online].2006. pp.16. Available from: PEPFAR: Reports. PEPFAR Reports: Report on Gender-Based Violence and HIV/AIDS PDF.

Harassment and Bullying (i.e "emotional abuse") can lead to:

National Institute of Health.NIMH. The Numbers Count: Mental Disorders in America. 2010. Available from: Article.

Why engage in activity that can increase the numbers? By the way, the numbers cause increased "disability" claims in the USA and Canada. Does the average individual in society truly want the human race to environmentally evolve to "the greatest emotional abuser" wins the prize? As we know, women have a tendency to lust after the "bad boy" mentality, but most don't want to marry the "bad boy".

In addition to My Gather Network: Quidnunc Simcha, I am a Guest-Editor and "Conversation Starter" at Conversations for a Better World, Chris Harding, which is a shared blog on population, gender and health, and provided by United Nations Population Fund Website.

Your Gather

Conversations for a Better World

You should consider contribution to Conversations for a Better World as well! The more diverse the discussions the better the results in most instances. Although time to a solution will increase significantly, the final result is usually better for humanity.