A Guide to Drug Manufacturing


Drug manufacturing can be divided into four key stages: drug discovery, drug design, drug trials, and drug production:

Drug Discovery

Target Validation: Allan B. Haberman, Ph.D. describes target validation as the "determination that a target is critically involved in a disease process and that modulating the target is likely to have a therapeutic effect." In Genetic Engineering News, Dr. Haberman suggests that the best method to identify "druggable" targets is through basic biomedical research. He also states that, "The determination of a target's druggability will depend in part on how much a company is willing to invest in time and in money to develop (or partner for) novel strategies for developing these compounds and on the creativity of the company's researchers."

High-throughput screening: According to Innovaro Pharmalicensing, "In terms of definition, high-throughput screening can be considered the process in which batches of compounds are tested for binding activity or biological activity against target molecules. Test compounds act as inhibitors of target enzymes, as competitors for binding of a natural ligand to its receptor, as agonists or antagonists for receptor-mediated intracellular processes, and so forth. High-throughput screening seeks to screen large numbers of compounds rapidly and in parallel."

Physical Characterization of Pharmaceuticals: If your business is not equipped to assess the physical characterization of new drug products, you can contact a CRO such as ParticleSciences.com, a Drug Development & Research Company.

Orphan drug discovery: First, you may want to search the FDA Orphan Drug Designations and Approvals database. For more information about applying with the FDA to designate a drug as an orphan product, please visit the FDA web site. You can also visit Orphanet, the portal for rare diseases and orphan drugs to learn more about the topic.

Ethnomedical Research: For recent journal articles about ethnomedicine, search PubMed for Medicine Traditional[Mesh] or consult the Journal of Ethnobiology and Ethnomedicine.

Drug Design

Lead Optimization: According to Genetic Engineering & Biotechnology News, "Lead optimization aims at enhancing the most promising compounds to improve effectiveness, diminish toxicity, or increase absorption. Many of the technologies for lead discovery overlap with lead optimization as researchers attempt to incorporate the best drug characteristics early in the process."

Assessment of Drug Absorption: The National Library of Medicine's MeSH entry describes absorption as, "The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy." Recent scientific research articles about absorption can be found by search PubMed for the MeSH term absorption: http://www.ncbi.nlm.nih.gov/pubmed?term=Absorption[Mesh]. For more information about aborption, you can consult the Merck Manual: Drug Absorption.

Assessment of Drug Administration Routes: According to the Merck Manual, "Drugs are introduced into the body by several routes. They may be taken by mouth (orally); given by injection into a vein (intravenously), into a muscle (intramuscularly), into the space around the spinal cord (intrathecally), or beneath the skin (subcutaneously); placed under the tongue (sublingually); inserted in the rectum (rectally) or vagina (vaginally); instilled in the eye (by the ocular route); sprayed into the nose and absorbed through the nasal membranes (nasally); breathed into the lungs, usually through the mouth (by inhalation); applied to the skin (cutaneously) for a local (topical) or bodywide (systemic) effect; or delivered through the skin by a patch (transdermally) for a systemic effect. Each route has specific purposes, advantages, and disadvantages."

For a list of the advantages and disadvantages of common routes of administration, visit Nursingcrib.com.

Assessment of Drug Distribution

According to the Merck Manual, "Distribution is generally uneven because of differences in blood perfusion, tissue binding (eg, because of lipid content), regional pH, and permeability of cell membranes. The entry rate of a drug into a tissue depends on the rate of blood flow to the tissue, tissue mass, and partition characteristics between blood and tissue. Distribution equilibrium (when entry and exit rates are the same) between blood and tissue is reached more rapidly in richly vascularized areas, unless diffusion across cell membranes is the rate-limiting step. After equilibrium, drug concentration in tissues and in extracellular fluids are reflected by the plasma concentration. Metabolism and excretion occur simultaneously with distribution, making the process dynamic and complex."

Assessment of Drug Metabolism:

The Merck Manual states that, "Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization; whatever the process, the goal is to make the drug easier to excrete. The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver. Drug metabolism rates vary among patients. Some patients metabolize a drug so rapidly that therapeutically effective blood and tissue concentrations are not reached; in others, metabolism may be so slow that usual doses have toxic effects.  Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly chronic liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism)."

Assessment of Drug Excretion:

According to the Merck Manual, "The kidneys, which excrete water-soluble substances, are the principal organs of excretion. The biliary system contributes to excretion to the degree that drug is not reabsorbed from the GI tract. Generally, the contribution of intestine, saliva, sweat, breast milk, and lungs to excretion is small, except for exhalation of volatile anesthetics. Excretion via breast milk, although not important to the mother, may affect the breastfeeding infant."

Drug Trials

Working with the FDA: For basic information about working with the FDA, visit FDA Basics for Industry. The FDA also offers a glossary of terms.

Manufacturing for Clinical Trials: If you need help to manufacture drugs according to the FDA's cGMP (Current Good Manufacturing Practices), Particle Sciences can offer smooth results for both small toxicology studies and full-blown clinical trials.

Clinical Trials Databases: ClinicalTrials.gov is a widely used registry and results database for clinical trials. CenterWatch.com also offers a database for clinical trials.

Drug Production

Drug production resource: PharmaManufacturing.com, the Digital Resource of Pharmaceutical Manufacturing Magazine, offers guides to Facilities & Support, the Facility of the Future, Automation and Control, Aseptic Processing, Drug Delivery, Packaging, Process Operations, Quality Assurance Control, cGMPs and Compliance, and more.

Environmental Regulations for the United States: You can visit the EPA web site to learn more about their regulations for the pharmaceutical industry.


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