Guidelines and Regulations

Introduction:

Everything related to the production of drugs is based upon a collection of Pharmacopoeia. These contain both guidelines and regulations and are a great source of information (though at times, some interpretation is needed).

What is a Pharmacopoeia?

This is a collection of drug information that includes how to prepare and test drugs.

The information may be specific to certain drugs eg Gramicidin is required to be assayed using the turbidimetric method. While other information may be generic, eg .an antibiotic may be tested via several different but comparable agar diffusion methods.

What is a guideline?

From a regulatory perspective, a guideline provides information on what is best practice. Guidelines are suggested ways to operate, though are not legally binding or enforceable ways to operate. Guidelines tends to use the word should a lot. When you read should in a guideline or regulatory document, it is an optional state of operation.

Despite this, if possible, guidelines should be followed as auditors will tend to follow these when auditing. It helps if you are aware of the applicable guidelines and have an explanation as to why you are deviating. i.e. why your way has been shown to be better or why your way is equivalent to the standard industry practice. Often, when a drug is registered, the product dossier will be specific as to the method by which the product is tested. This can lead to issues should the company modify the test method, or the regulations specify a different method in the future.

What is a regulation?

A regulation is a legally binding requirement.

Regulations tend to say must often. Eg, “all microbiology staff must have appropriate training for their task.” Or “Product A must be tested for A, B and C and must meet the assigned specifications”. When you read must in a guideline or regulation, you have to follow the directions given.

Why Were Guidelines and Regulations Introduced?

Due to undesired side effects, poor efficacy, false and or misleading claims and inconsistent drug makeup, modern pharmacopeia were developed. (The earliest pharmacopeia is purported to have been in circulation around 1020).

It is interesting that for “holistic” medicine and the bulk of unregulated, but TGA approved products such as those derived from plants or various proteins with no direct medical application, the labels can say pretty much anything and can use words such as “used traditionally by monks in Upper Mongolia to treat fungal nail infections for millenia” to support the action of the product even though there is often little of no scientific evidence that the product has any efficacy.

Cases resulting from poor regulation:

  • Chloroform (1847-48) – one of the first anaesthetics in use. Had a tendency to produce fatal cardiac arrhythmia. Here it’s use “fell out of favor” when too many people died and predates modern drug regulation.
  • pDinitrophenol 1930’s diet pill. Overdose (via self medication) = death by raised body temp. Reclassifying some drugs as prescription only was done for drugs deemed too dangerous for self medication.
  • Ethylene glycol (1937) used as base for sulphur based antibiotic >>> kidney failure/convulsions/severe pain >>> death. Toxicity testing mandated by FDA.
  • Thalidomide (1950/60) >>> birth defects >>> clinical trials introduced for pregnancy as response (Europe/Britain).
  • Dalkon Shield intrauterine device (US 1970’s) caused injuries and lead to regulation of medical devices.

Much of the regulations were introduced after the event due to public pressure. This is despite various bodies trying to introduce the regulations before disasters hit (being proactive is this author’s preferred way of doing things).

Regulations have also been introduced to ensure that products match what the label claims. This ensures that the product and dose are correct and also that you have tablets in a tablet box, not a cream or a liquid, for example. Regulations also ensure product consistency, batch to batch.

With the many regulations, it can sometimes be difficult to meet them. This is mainly due to different countries having different requirements. However, this is being addressed and since the early 1990’s the EP, USP and JP have been working towards harmonisation.

Who are the main regulatory bodies?

Generally each country will have their own governing body. The main ones applicable to pharmaceutical development and manufacture are:

Appendix (other sites of interest):