Pharmaceutical Industry: An Over view

Pharmaceutical are medicinally effective chemicals. Which are converted to dosage form suitable for patient to imbibe? Usage of pharmaceuticals is governed by the underlying medical science.

The three primary medical sciences are as under

* Allopathy or modern medicine has gained global popularity

* Unani, having Chinese origin, is present in southeast Asia

* Homeopathy, founded by German physician, is also fairly popular

World over the pharmaceutical industry is focused on Allopathy, the modern medical science, while other modes of medical treatment such as homeopathy, Ayurveda and

Unani are more prevalent in third world countries

A) Bulk Drugs (Chemical Forms)

B) Formulation (Final Dosage forms)

Bulk Drugs

Bulk drugs are medicinally effective chemicals they are derived from 4 types of intermediates (raw materials) namely

Plant derivatives (Herbal products)

Animal derivatives e.g. insulin extracted from bovine pancreas

Synthetic chemicals

Bio genetic (Human) derivatives e.g. Human Insulin

Bulk drugs discovery requires intensives and expensive research. New drug are patented by the innovator to ensure commercial gains on his R&D investment. When a drug goes off patent it becomes generic. Bulk drug can be broadly categorized as Under patent, Generic or off Patent.

Formulation

Doctors post diagnosis to cure a disease or disorder in the patent primarily prescribes formulations, to prevent misuse or incorrect administration. Most formulations are disbursed by pharmacies, only under medical prescription and these are called ethical products. However some formulations such as pain balms, health tonic, etc. can be purchased by users directly. These are called Over-The-Counter (OTC) Products. Formulations can be categorized as per route of administration to Patient, Viz:

Oral: tablets. Syrups, capsules, powder etc

Topical: Ointment, cream, liquids, aerosols that are applied on the skin

Potentials: sterile solution injected in an intravenous or intramuscular fashion

Others: Eye drops. Passerines, surgical dressing etc

Manufacturing Process

Bulk drugs are prepared by appropriate chemical reactions of natural/synthetic intermediate under controlled conditions. Formulation manufacture is a batch mixing process. Right dosage of the bulk drug (active ingredient) is compounded with compatible, Packed as per the physical form bottles for (liquids), blister strips (For tablets/capsules) or ampoules (for powder). Each formulation pack has the expiry date and storage instruction printed on it. Stringent quality control is exercised at all stages

Therapeutic segment

For ease of prescription, bulk drugs and their formulation are classified as per their end use i.e. therapeutic effectiveness against a particular disease or ailment e.g. medicines are categorized as anti-ulcer, anti-tuberculosis etc

Research & Development

The importance of R&D patent in the Global pharma industry and changes in patent laws to be enforced under WTO are highlighted in the subsequent paragraph. Pharmaceutical industry is driven by the global need to conquer diseases or improve upon the existing treatment. An in depth understanding of human physiology and diseases mechanism is a pre-requisite to pharma R&D.

To facilitate research, companies usually concentrate on selected therapeutic areas; such as anti-ulcer, anti-cancer, etc. Major diseases for which new drugs are continuously being researched globally are AIDS, Alzheimer’s disease, Arthritis, Cancer, depression, diabetes, Heart disease, Osteoporosis and stroke.

A) Basic Vs Process R&D

Basic research deals with discovery/invention of new medicinally effective chemicals. Process R&D is basically reverse engineering of molecule through slight process modification. Basic research is both time and cost intensive hundreds of molecules need to be analyzed to determine possible effectiveness. Following such laboratory testing, actual clinical trials are then carried out to determine the drug efficacy on patients. The process thus requires around 12-15 years and costs US$ 350-400 Million per year. New Chemical Entity (NCE) process R&D is far easier while its cost are negligible compared to basic research.

B) Patent and WTO Regulation

“Patents” are a vital aspect of the global Pharma industry. Patent protection is essential to spur basic R&D and make it commercially viable. But only the developed nations endorse product patents. Most third world countries have patent laws, but enforcement is totally lax.

Some developing nations like; Pakistan, India Egypt and Argentina allow only process patent registration. As a result, Pharma R&D is concentrated amongst the Pharma Multinational

Companies in USA, JAPAN AND EUROPE. The leading MNCs have a geographically widespread market reach, spanning almost the entire globe; hence their high R&D costs can be spread over a large user-base.

A researcher undertakes patent registration once a molecule shows some promise of therapeutic effectiveness. Patent life-counter starts running from the day the patent application is made. The patent office then starts the process of establishing that the molecule is unique.

The steps involved are:

1) Within 18 months of filing the application, a brief write up of the molecular structure and its therapeutic utility is published as a public document.

2) Patent office thereby invites objections, if any, from third parties e.g. competitors.

3) Objections received are conveyed to the applicant who has a chance to defend or modify his claim to originality.

4) The modified claims are republished and once again objections are invited,

5) Once the patent office is satisfied about the applicant’s claim, it grants the patent.

The whole process takes 4-5 years due to significant back-log in the patent registration office. Once a patent is granted in one of the developed nations, it is relatively easier to get it in other countries. Also certain patent authorities have coverage over a large part of the European sub continent. Due to pressure from the developed countries, across the world uniformity in patent laws is being implemented under WTO (World Trade Organization). Presently; different countries have different patent types and life periods.

WTO has decided upon a product patent life of 20 years in all countries. However, to ensure a smooth transition and provide ample time to local manufacturers in the developing countries, for gearing themselves, a moratorium, up to the year 2005, has been provided. So, the new product, i.e. drug introduced after this date, will have to be accorded product patent protection even in countries like Pakistan and Argentina.

New drug Approval (NDA)

Prior to launching its products in any country, a Pharma company undertakes patent registration to protect its own interest. To protect the interests of the consumers, it is necessary that the product be approved by the drug Authorities in that country.

A new drug application filed with the drug authorities-(such as FDA in US or CSM in U.K), detailing of the new molecules therapeutic properties is done and then the clinical trials are carried out in 3 stages.

1) Animal toxicity (testing on Animals)

2) Trials on few select volunteers.

3) Trials on a larger scale in hospital/Institutions.

Drug Authorities approval has to be taken at each stage and the product can be launched only when all three trial stages are completed successfully. Once a new product has been launched in any of the developed countries like USA, JAPAN, EUROPE, it takes relatively lesser time to get approval from drug authorities in other countries.

MEDICAL RESEARCH

Research is one of the most important fields of medicine. It provides health care professionals with new knowledge and technology for better diagnosis, treatment and prevention of disease. Medical research often combines medicine with related fields of biology, and is called Bio-medical research.

Research can be basic or applied. Basic or Fundamental research has no immediate practical application. For instance, basic cancer-cell research may try to identify gene mutation that turns a healthy cell into malignant. While this information does not have immediate clinical value, it generates knowledge that often leads to better care for patient. Applied research has a specific practical goal, such as development of a better drug for breast cancer, the early stages of biomedical research usually occur in laboratory.

As scientist gains more knowledge in particular areas, they begin study on human. These studies often take place in hospitals clinics and are called Clinical research. Clinical research

usually is performed by multidisciplinary teams, rather than by an individual scientist working alone.

These groups of men and women have knowledge and skill in different areas, or disciplines, of science. A multidisciplinary biomedical research team may include biochemist, geneticist, physiologist, and physician. Each member approaches the problem from a different side and shares knowledge with the group. This multidisciplinary approach increases the chances of solving problem or developing a new treatment.

Clinical Trials

One of the greatest advances in medicine was the introduction of a new research technique called the controlled clinical trials, during the mid-1950s. It is used to determine if new drugs and other treatment are safe and effective. In the controlled clinical trials, one group of patients - the treatment group, is given an inactive pill (placebo) or the best standard treatment. Researcher then compares the two groups over a period of time. The data collected is put through rigorous statistical technique to determine whether the new treatment is safer and more effective than the standard therapy or no treatment. Most clinical trials are conducted on a blind or double blind basis.

In blind trials, patients do not know whether they receive the new drug or a placebo. In a double blind trial, neither patient nor the physician knows who is receiving the new treatment. The secrecy is important because if the patient knows that he is taking a powerful new drug, he may expect to feel better and report improvement to the doctor. A researcher, who knows that a patient is receiving the test treatment, may also see improvements that really do not exist.

Clinical trials are usually randomized. Researchers put patients into a treatment group or control group at random. This helps to assure that neither group contains an excess of patients with severe disease. A drug may appear more effective if the treatment groups were packed with patients who had only mild symptoms.

The results of clinical trials are subjected to peer-review. Researchers publish their result in scientific journals or present them to an audience of other scientists who are their peers. Thus the scientists who are not involved in the research get a chance to identify potential errors.