There are no guarantees when a veterinarian unkowingly picks up a bulk compounded , pirated drug, Dr. Joseph J. Bertone offers his insight.
Veterinarians have enjoyed a remarkably positive reputation with the public. However, the use of pirated drugs has put that good reputation dangerously at risk. These drugs may be less expensive, but they also are of poor quality, highly variable in nature and of unknown content or stability. The use of pirated drugs removes the essential information in clinical pharmacology and the application of therapeutics, i.e., what have you administered to the patient? With pirated drugs, neither you nor the pirate knows what you have administered. Use of pirated drugs is, by definition, substandard veterinary care.
Photos 1A and 1B: A product that expired five years ago. Although not a pirated product, this is clear evidence of the pirate's ignorance or unethical nature.
What is the essential information necessary in medical therapeutics?
Answer: What and how much have you administered!
All clinical practice, clinical outcomes and pharmacologic data are based on that premise. If you don't know that information, then you are stabbing in the dark in applying a therapeutic. If you don't know what you have administered, then it is best "to apply the drug liberally per foot."
Table 1: Omeprazole content as a percent of the label indication from 10 different drug pirates.
Question: How does a practitioner know what they have administered?
Answer: The best means is by administering an Food and Drug Administration (FDA)-approved drug. These include pioneer and generic drugs and registered products. All of these are manufactured under Good Manufacturing Practices (GMP) legislation and guidelines. GMP laws and guidelines provide for the assurance of the products' quality, consistency, strength, purity and stability.
Pioneer drugs are the original product under which drug sponsors collected efficacy and safety data for FDA approval (i.e., RompunTM). Generic drugs are allowed to be marketed based on matching pharmacokinetics to the pioneer (bioequivalence) and the determination that the other constituents of the product (excipients) provide no safety risk (e.g., xylazine HCl injection). As with pioneer products, generic products require FDA approval and undergo GMP manufacturing and assurance. Examples of registered products include intravenous fluids and vitamins with no claim, but are allowed to be marketed by FDA and still undergo GMP manufacturing criteria.
Table 2: Meloxicam content as a percent of the label indication from 19 different drug pirates.
A common misconception among veterinarians, and often indicated by drug pirates, is that pirated drugs are generics. That is wrong!
Pirated drugs can have no claim to drug quality, consistency, purity and stability. The bulk product is often made in laboratories in China, India and Pakistan. These laboratories do not meet the requirements for GMP manufacturing as bulk drug sources. No bulk drug intended for use in veterinary species is allowed to be imported into the United States. Therefore, all bulk chemicals used in drug piracy have been imported illegally.
Our education is, unfortunately, weak in pharmacology as it relates to drug formulation. A drug is far more than the active ingredient. In fact, the pharmacodynamics of a drug is heavily dependent on the excipients (i.e., inert substances, preservatives, etc.) that make up the formulation. Under GMP laws and guidelines, excipient quality is scrutinized to the same detail as the active ingredient.
Table 3: Clenbuterol content as a percent of the label indication from 7 different drug pirates.
Accurate shelf-life studies for an FDA-approved drug require GMP manufacturing, so that the drug can be assured of its composition. Then once packaged, the drug undergoes accelerated testing for stability under extreme environmental situations before the drug is approved and given a shelf-life period. After that, aliquots of each batch are held back and tested over time. The cost for just the accelerated study for a single dosage size will be approximately $150,000. Since pirated products are not GMP manufactured, even if one were to run accelerated studies, they would have no value because you could not be assured of the product's make-up and consistency from batch to batch. So when pirates label their products with shelf-lives that exceed the period of the prescription (sometimes years) they are ignorant or unethical (Photos 1A and 1B, p.17).
Pirated drugs compare very poorly - they are of poor quality, strength and purity (Tables 1, p. 17, 2 and 3). As an example, you intend to administer drug X at a dose of 10 mg/kg. When you use an FDA-approved drug produced under GMPs (which is all of them), the dose you are administering will fall in the range of 9 to 10.5 mg/kg for most drug products. That is clinically reasonable.
Based on information collected to date, when you use a pirated drug, and if you dose on volume for 10 mg/kg, the dose range you will administer will be 0 to 17.6 mg/kg with possible impurities and other "stuff" in the mix for which you can't account. Also there is no guarantee of purity and shelf life of the mixture. In Tables 2 and 3, the content of active ingredient was evaluated in samples from multiple drug pirates (disguised as compounding pharmacists). The approved formulation varies between 90 percent and 105 percent of the label indication. Tested pirated articles to date have fallen in the range of 0 to 176 percent of the label indication. The variation is astounding. However, do not believe that these numbers are repeatable per pharmacy. Since the active ingredient from overseas sources is of variable quality, on the next round of batch testing, the high content pirated drug may look like the low content pirated drug and vice-versa.
Photo 3: A combination of "omeprazole" and bismuth subsalicylate in a water-based paste. Both BSS and water rapidly degrade omeprazole.
It makes sense that pirated drugs are poor quality. Pirates are unethical (they care little about you, your patients or your clients) or unknowledgeable (they believe they produce products to acceptable clinical standards).
Use of pirated products is not quality veterinary medicine.
The negative effects of pharmacy should now be obvious. When you use a pirated product, you are administering a poor, unacceptable quality drug at an unknown dose and questionable purity and sterility. In addition, this reduces incentive by the regulated pharmaceutical industry for scientific development of quality products for veterinary species. Several animal health sponsors have not moved forward with development of needed veterinary drugs because of the risk of having the product compounded. As an example, see Photo 3. That data was collected within a few weeks of the drug's FDA approval. At that point, the sponsor was a small player in the marketing and distribution of the product. Why would a pharmaceutical company want to invest millions of dollars into something when pirates have to invest so little? Pirates violate the public trust with the veterinary profession's help.
Legitimate compounding pharmacy is not drug piracy. In fact, the American College of Veterinary Pharmacists indicated they are appalled by this activity and they are being inadvertently and adversely affected by this practice. Legitimate pharmacy drug compounding is based on the extent of knowledge in compounding chemistry and ethical behavior. They provide the best quality possible under the limited facilities and controls of a compounding pharmacy. It is difficult to identify the extent of a pharmacist's knowledge in compounding and formulation chemistry. However, the pharmacist's ethical behavior can be evaluated. Good compounding pharmacists do not drug pirate.
You have no idea of the content of active ingredient or impurities in a pirated drug product. You also have no idea of the pharmacokinetics of the formulation. Drug piracy is an indication that the pirate is unethical or unknowledgeable. These drugs have no assurance of quality, safety and efficacy.