The Jungle of Guidelines - EU Part 1

Written By Annett Mueller

Hello and welcome to the jungle of guidelines. You look a bit lost… 

Oh, I see. They told you that you should read the guidelines and now you don’t know where to start.

Well, you are not alone. The jungle of guidelines is mysterious and not easy to navigate. Many before you have given up. Some we have lost.
But I see potential in you. You have that look of a real hero. So let me be your guide through the guidelines.

Who am I? Oh, I beg your pardon. They call me “Will of Wisdom” and I am a Qualified Person (QP) in these lands.

That means in Europe I am basically a divine being and in some other parts of the world they don’t acknowledge my existence. Lucky for you (and me), we are in Europe. 

Here we have a dense jungle of regulations, directives, guidelines, national laws and many, many opinions. It’s confusing, but that’s why I’m here, to help you find a path through it, one step at a time.

European Legislation

First things first, the rules and regulations from the European Union concerning pharmaceuticals can be found in a collection of texts known as EudraLex.

Here is your first quest: Open the EudraLex website and put it next to this article. So, you can explore a little and see what it actually looks like.

Directives & Regulations (Eudralex Volume 1 and 5)

You’ll notice that Eudralex consists of Volumes 1 to 10. Initially, we need to acknowledge volumes 1 and 5.

This is because the directives and regulations (the actual body of the legislation) are compiled in Volume 1 (for human use) and Volume 5 (for veterinary use):

  • Volume 1 - EU pharmaceutical legislation for medicinal products for human use

  • Volume 5 - EU pharmaceutical legislation for medicinal products for veterinary use

It is important to note that there are two types of legislation documents in the European Union - Directives and Regulations.

What’s the difference between them?

Well, if something is a Directive it is supposed to give the member state a direction to what is expected but let each member state decide how they implement this into their national law.

A Regulation on the other hand is binding and must be applied in all member states. To make it more fun, member states can have additional laws on top.

To help you remember try using the mnemonic “Directives give directions, while regulations are rules”

Guidelines (Eudralex Volume 2, 3, 4, 6, 7, 8, 9, 10)

The rest of the Volumes are guidelines. These are meant to be supporting documents but in fact they are where the magic happens. There is an expectation that pharmaceutical companies in all European member states comply with these guidelines.

Here is an overview of the volumes, but don’t worry we are only going to look at Volume 4 for now.

  • Volume 2 - Notice to applicants and regulatory guidelines for medicinal products for human use

  • Volume 3 - Scientific guidelines for medicinal products for human use

  • Volume 4 - Guidelines for good manufacturing practices for medicinal products for human and veterinary use

  • Volume 6 - Notice to applicants and regulatory guidelines for medicinal products for veterinary use

  • Volume 7 - Scientific guidelines for medicinal products for veterinary use

  • Volume 8 - Maximum residue limits

  • Volume 9 - Guidelines for pharmacovigilance for medicinal products for human and veterinary use

  • Volume 10 - Guidelines for clinical trial

GMP Guidelines (Volume 4)

When people refer to GMP guidelines they usually mean Volume 4.

Try not to scream when you open the site and see the number of documents. As you can see Volume 4 consists of 6 section:

  • Introduction

    Here you find links to the actual regulations and directives that apply to this part of the jungle. Do. Not. Go. There. Yet. – Preserve your strength!

  • Part I // Basic Requirements for Medicinal Products

    In its essence these documents describe what you need to comply with for finished products ( = Drug Product). It’s your basic quality system. You should read all of the chapters here. Yes, ALL of them. They are not too long. Between 4 and 12 pages. You only have to read them, not memorize everything.

  • Part II // Basic Requirements for Active Substances used as Starting Materials

    Good news is, it’s only one document. Bad news, it’s a long one (49 pages).

    However, most of the information in this document is the same as in part I. If the company you work for does not produce finished products itself but makes active substances that other companies use as starting materials for their products, you can consider reading part II instead of part I. However, I would advise that it’s good to read part I as well.

    Fun Fact - The term active substance has many aliases. Active Substance = Active Ingredient = Active Pharmaceutical Ingredient (API) = Drug Substance.

  • Part III // GMP related documents

    Yeah, well … It's a selection of documents. I’m afraid it will remain a mystery why these documents are the chosen ones and others are not. For now, just have a look at them and see if anything is immediately relevant for you.

  • Annexes

    Now we get to the really interesting part! Annexes are additional documents that apply to both drug substance and drug product but not all of them are relevant for every company.

    Have a look and decide whether or not they apply to your situation.

  • Part IV // GMP requirements for Advanced Therapy Medicinal Products (ATMP’s)

    OF WHAT?!? … Calm down. This guideline is only applicable to you if you work with medicinal products that are based on engineering of genes, cells or tissue (e.g. gene therapy or manipulating cells/tissue before giving them to a patient).

  • Other documents related to GMP and GDP

    Some other documents that are GMP related, but for some reason didn’t make it into Part III. Have a look around. Definitely check out the Guidance on good manufacturing practice and good distribution practice: Questions and answers It links to a website where the European Medicines Agency (EMA) answers frequently asked questions on GMP/GDP. We talk about EMA when we enter the deeper parts of the jungle.

Ok, by now your head is probably spinning and you are feeling pretty overwhelmed. (If not, make sure you haven’t accidentally fallen asleep.) I wish I could say that this is the worst part and it will all be downhill from here. Unfortunately, this is only the beginning. But you wanted a challenge, right? Right?

To make things a bit easier for you I created a worksheet / reading list and with that I am sending you on another quest. Farewell for now. I wish you good fortune. I’m sure we will meet again.

Annett Mueller