Tag Archives: FDA guidance

How the Pharmaceutical Industry became into existence?

The Birth of the Pharmaceutical Industry can be traced back to 1850 – 1875 where the first “authentic” drug was developed by extracting agents from plants.

In those years, there were also developed the microbial theory of disease, medicines and homoeopathy patent and there heavy use of powerful purgatives and cathartics medicines.

By 1875, the Drug Development becomes a science and the first synthetic drug was introduced. By 1900, vaccines and antitoxins form the basis of the new pharmaceutical industry.

From 1900 to 1925, began what is now known as the pharmaceutical century. The U.S. Pure Food and Drugs Act was passed (known today as the FDA) and the development of hormonal and chemotherapy was introduced.

After 1925, it began what is known today as the Antibiotic and Regulatory Era. Vitamins, antimalarials, anticarcinogenic compounds and anti-infectives discoveries were made. The FDA gains independence as a regulatory agency and is given compliance responsibility.

From 1950 thru 1975, a new generation of the drug became apparent. Vaccines for polio became mandatory, oral contraceptives appears on the market and cardiovascular therapies.

Also, an amendment to the Federal Food Drug and Cosmetic Act of 1938 Act was signed by President Kennedy to ensure that consumers will not be the victims of unsafe and ineffective medications. Additional information about this Act can be read here: Kefauver-Harris Amendments

The Globalization of the Pharmaceuticals industry started from 1975 thru 2000. New drugs therapies, new antiviral drugs, and the development of new drugs by biotechnology companies were in global high demand.

By 2000, over 2.8 million people participated in over 50,000 clinical trials and more research and development funding was increased.

R&D Expenditures by Body System

R&D Expenditures

Cost (Billions) Body System
7.0 Central Nervous System
6.0 Cancer, endocrine and metabolic
4.5 Cardiovascular
3.5 Infectious Disease
2.5 Biological and vaccines
5.3 Other

Current Trends in the Industry since the late 2000s

Biotechnology Medicines
Drug Intervention Targets
Vaccines

 

Role of Generic Drugs
Generic drugs account for over 47% of prescription drugs in the market in which 43 major prescription drugs come off patent by 2005.

What does this mean for pharmaceutical drugs?
Between 40% – 60% of sales are lost to the generic brand within the two years of coming off patent.

Factors that will impact the R&D future:

  • There has been over 40 mergers and acquisitions since 1985
    • Sanofi and Synthelabo
    • Zeneca and Astra
    • Monsanto and Pharmacia
    • Roche and Genentech
  • Employment grew at a 3% rate per year

Total Drug Development Time (Years)

Summary:
On average, it takes at least ten years for a new medicine to complete the journey from initial discovery to the marketplace, with clinical trials alone taking six to seven years on average. The average cost to research and develop each successful drug is estimated to be $2.6 billion.

Pharmaceutical Regulation

In 1902, about 10 children die after receiving a vaccine shot. The BIOLOGICS CONTROL ACT was passed to ensure purity and safety of serums, vaccines and similar products used to prevent or treat diseases in humans.

In 1906, “The Great American Fraud” reveals patent medicines laced with addictive drugs, toxic additive and alcohol.

In 1912, Public outcry over the sales of “snake venom” and other wonder cures.  The SHERLEY AMEND was passed to prohibit labelling medicines with false therapeutic claims intended to defraud the purchaser.

In 1927, the government forms a separate law enforcement agency called the Food, Drug and Insecticide Agency.

In 1937, about 107 people, including many children die after drinking a syrup called Elixir of Sulfanilamide. Due to safety concerns, The Federal, Food, Drug and Cosmetic Act (1938) was passed as the first attempt to regulate cosmetics and medical devices.

In 1962, the sleeping pill “Thalidomide“, developed what is known today as Grunenthal Pharmaceutical in Germany, resulted in thousands of birth defects in Western Europe. The KEFAUVER-HARRIS Drug Amend was passed to ensure drug efficacy and greater drug safety.

In 1983, the ORPHAN DRUG Act was passed enabling the FDA to promote research and marketing of drugs needed for treatment of rare diseases. This year there as an outbreak of HIV / AIDS cases.

In 1988, The FOOD and DRUG ADMINISTRATION ACT were established as the FDA under the Department of Health and Human Services.

In 1992, the pharmaceutical industry complained that life-saving drugs were being reviewed too slowly by the FDA. The PRESCRIPTION DRUG USER FEE ACT (PDUFA) is made into law.

Source:

Image: Courtesy of Google image

FDA website

Private information for college researched in the 2000s.

Eliminating Informed Consent on Human Experimentation with Vaccines and Drugs

The 21st Century Cure Act would demand that the Food and Drug Administration (FDA) add an exemption from informed Consent requirements for those clinical trials that pose no more than minimal risks and the appropriate safeguards protecting the right, safety and welfare of subjects.

Informed Consent Waiver

The above can be found in section 3024 – Informed Consent Waiver or Alterations for Clinical Investigations.

So what they are saying now they don’t have to obtain informed consents to test vaccinations or drugs on humans beings if it has been determined that the proposed pose no more than minimal risks.

Let’s review the Exemption  for Devices for Investigational Use

(g)(1) The purpose of this section to encourage to the extent consistent with the protection of public health and safety and ethical standards, the discovery and development of useful devices intended for human use and to that end to maintain optimum freedom for scientific investigators in their pursuit of that purpose.

In other words, you can get an exemption for certain conditions.

Question: if you don’t have informed consent in clinical trials experimentation on people, then how does anyone knows you are not part of an experiment?

If sponsors and clinical researchers not longer has to tell you that you are part of it or get your consent to informed you what they are doing? That may sound a little crazy.

Further source of research:

The 21st Century Cures Act Implications

Say Goodbye to Vaccine Safety Science by Barbara Loe Fisher

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“Copyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for “fair use” for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use.”

Data Management Plan – Database Archive

Indicate how you intend to archive and share your data and why you have chosen that particular option.

The DMP should outline specific information regarding the organization’s procedures for archiving the electronic records.

Good practice for digital preservation requires that an organization address succession planning for digital assets.

Which criteria will you use to decide which data has to be archived? What should be included in the archive?

Type of data (raw, processed) and how easy it is to reproduce it. Also consider archiving audit trails as long as the records are (CRF Part 11, Section 11.10).

Does the archive have specific requirements concerning file formats, metadata etc.

It is recommended to use open source formats such as PDF-PDF/A, ODM-XML or ASCII type of files.

anayansigamboa

 

 

 

 

Who is responsible for the data after the project ends?

Sponsor, CRO, Vendor? All should be documented on the DMP. Once database is locked, within a reasonable time and after data submission to a regulatory agency, you want to archive your database for long term storage and recovery.

While most data submitted to regulatory agencies are available in SAS formats, there may be times when going back to the original data format may be required.

Even though the easiest way to make sure data is available after database lock is to archive this data in the built in structure as the current system. For example, for Medidata Rave studies, trials are built on on top of SQL server, hence, you should consider archiving the old studies in a compatible format of SQL Server, without any transformation or data manipulation = raw data.

Other formats for data archive can be considered are ODM XML, PDF-PDF/A or ASCII A-8. These are some options for long=term storage. FDA says in the guidance document for 21 CFR Part 11, ‘scope and application – section C.5″, “FDA does not intend to object inf you decide to archive required records in electronic format to nonelectronic media….As long as predicate rule requirements are fully satisfied and the content and meaning of the records are preserved and archived, you can delete the electronic version of the records”.

Archival Plan

For archiving data, this plan should list all the components of the orginal system that will be included in the archive and the formats being used for their storage.

The best practices for clinical data archiving in clinical research are no different from those for archiving any other kind of industry.

 

 

-FAIR ;USE-
“Copyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for “fair use” for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use.”

Anayansi Gamboa has an extensive background in clinical data management as well as experience with different EDC systems including Oracle InForm, InForm Architect, Central Designer, CIS, Clintrial, Medidata Rave, Central Coding, OpenClinica Open Source and Oracle Clinical.

A Risk-Based Approach To Monitoring

A risk is any uncertain event or condition that might affect your project. Not all risks are negative.

No single approach to monitoring is appropriate or necessary for every clinical trial. FDA recommends that each sponsor design a monitoring plan that is tailored to the specific human subject protection and data integrity risks of the trial.

Not all risks are negative
Some events (like finding an easier way to do an
activity) or conditions (like lower prices for certain
materials) can help your project! When this happens,
we call it an opportunity… but it’s still handled just
like a risk.

avoid_mitigate
avoid_mitigate
transfer_accept
transfer_accept

Image Source: Head First PMP, by Jennifer Greene, PMP and Andrew Stellman, PMP

FDA has also recognized this fact and come out with a “Guidance for Industry Oversight of Clinical Trial Investigations – A Risk Based Approach to Monitoring”. As per this guidance the objective of the guidance is “to assist sponsors of clinical investigations in developing risk-based monitoring strategies and plans for investigational studies of medical products, including human drug and biological products, medical devices, and combinations thereof”.

Unfortunately, a lot of people in the industry are speaking about risk-based monitoring, but few have a broad understanding of the whole life-cycle process. Great opportunities exist for savings, but then again, most EDC platforms dont work effectively with risk-based monitoring. Switching to risk-based monitoring increases rather than decreases work because it can break the EDC workflow – refuting much of the value of EDC.

In conclusion, Risk-based monitoring is yet another desperate attempt to deal with what all Electronic Data Capture (EDCs) systems have failed to deliver – quality of clinical data.

Source: FDA Guidance

Your comments and questions are valued and encouraged.
Anayansi Gamboa has an extensive background in clinical data management as well as experience with different EDC systems including Oracle InForm, InForm Architect, Central Designer, CIS, Clintrial, Medidata Rave, Central Coding, OpenClinica, Open Source and Oracle Clinical.

 

anayansi gamboa