I will now run through these in a little more detail.
The most common method of getting drugs into the body. Generally seen as convenient by the patient. The drug formulation needs to protect the active ingredient through the acids of the stomach. Once absorbed the drug passes through the liver where it will be metabolised.
These drugs are injected straight into the bloodstream and have a rapid distribution and effect. They also avoid the initial metabolism in the liver. They can be used for small administration of product via injection or for longer term dosage via intravenous bags. Due to the fact that these products bypass the body’s natural defence mechanisms they need to be sterile (free from micro-organisms).
Other specialised methods of injection also exist. These include:
- Intra-muscular injections (into the muscle)
- Subcutanious injections (into the skin layers)
- Intra-cisternal injections (into the lymph ducts)
- Intra-osseous injections (into the bone marrow)
- Intra-articular injections (into a joint)
- Intra-peritoneal injections (into the body cavity around the gut and intestines)
- Intra-arterial (into an artery) – normally you are injected into a vein
- Intra-cardiac (into the heart)
- Intra-cranial (into the skull)
These products are breathed in and are absorbed into the blood stream via the lungs. Examples include anaesthetic gasses, asthma inhalers and nebulisers. They do not need to be sterile, but aqueous inhalation products (nebulisers) often made and tested as if they were sterile. The USA required aqueous inhalation products to be sterile.
These products are applied directly onto the outer body surfaces. They include creams and ointments. The drug is not well absorbed through the skin and as such these products are used to treat the condition locally.
Here the product is administered into the anus (bum, bottom, anus, arse (whatever you want to call it)) in the form of a suppository. This is actually a very good route of drug administration due to the high qualities of blood vessels around the anus. Treat customer complaints from individuals who complain that a suppository doesn’t taste very nice carefully! The patient has put the product in the wrong hole!
Used as patches on the skin for long term dosing. Good if a steady amount of the drug is required over a period of time (the user can, for example, forget to take a tablet). Commonly used for smoking cessation products, hormone replacement and pain relief during late stages of cancer.
Here the product is absorbed under the tongue. The dry product is taken into the mouth where it dissolves. It is absorbed rapidly with quick onset of action. This method also avoids initial metabolism in the liver.
Here a sterile product is added to the eye. Eye care products must be sterile because the lens of the eye cannot repair itself as it has no blood supply.
Here products are added to the ear, usually to treat conditions of the ear such as ear infections and dealing with excessive ear wax.
These types of product are called pessaries and works as a similar way to a suppository. Their usage is restricted to about half of the world’s population – I can’t think why!
This topic and many others is covered in our on-line course on Medicinal Chemistry.
I hope this post is of interest. Dominic
Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.
Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.
While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.
About the author
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
Training courses on Annex 1
There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
Our 2-day course is updated for Annex 1 changes
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