By: Donagh Fitzgerald B.Prod Eng and Gerry Creaner B.Chem Eng. Last Updated: February 2024

Good Manufacturing Practices GMP

What are good manufacturing practices (GMP)?

Good Manufacturing Practices (GMP) are a set of product quality regulations that have the force of law and require that manufacturers and packagers of medicines and medical devices take steps to make sure their products are safe, pure and effective.

GMPs cover all aspects of production, from raw materials, factory and equipment, manufacturing, personal hygiene, training, packaging and labeling, record keeping, personnel, product testing, and addressing errors and complaints.

GMPs are the law of the land and failure to comply can result in severe consequences including product recall, seizure, fines, and in extreme cases, even jail time.

In this article, we are going to dig deep into GMPs and answer many of the misconceptions and misunderstandings about the use and application of GMPs on the factory floor.

BTW, if you want to get a solid understanding of GMP rules, regulations and guidelines, check out our 6-Week GMP Training For Beginners in the Pharmaceutical Industry.

Table of Contents

1) What Are Some Things a GMP Manufacture Must Do?

Good Manufacturing Practices establish minimum standards for the manufacturers of pharmaceutical and medical device products. Each manufacturing plant must:

  • set up a robust quality management system
  • have detailed written procedures for each process that could affect the quality of the finished product
  • obtain appropriate quality raw materials
  • establish operating procedures for consistently manufacturing safe medicines and medical devices
  • detect and investigate product quality deviations
  • maintain reliable testing laboratories
  • have a well-documented system to provide evidence that the employees are following the correct procedures at each step in the manufacturing process every time a product is made

The end result is that GMPs help make sure the patients get the right product at the right strength and that it is:

  • free from contamination
  • is correctly labeled
  • is sealed and protected against damage or tampering
  • is stored correctly

GMP regulations also help minimize or eliminate instances of contamination, mixups, and errors and protect the patient from purchasing a product that is not effective, dangerous or even deadly.

A key tenet of GMPs is that testing alone is not adequate to ensure quality, as quality cannot be tested into a product. Rather quality must be built into the process of everything from the development of the product to its manufacturing, to its distribution and storage, all the way until it is used by the patient.

For the most part, GMP requirements are general rather than specific, as every product and process are unique, and can be improved upon over time.

This allows each manufacturer to decide the best way to implement the necessary controls within the guidelines outlined in the regulations. It also allows companies to interpret the GMP regulations in a patient-centric manner which makes sense for each business.

2) Why are GMPs Important?

Medicines change the way that the body functions and so the public expects that they are safe, effective (that is that they work) and consistently manufactured to the right quality.

With most other manufactured products if something is wrong with the item, then the end user may spot the problem before they take or use the product.

This is not the case with medicines. It’s almost impossible for a medical professional, much less a patient to know through looking at or touching or smelling a tablet or an injection if it is safe to use before taking it.

This risk is further compounded as when we take medicines and inject them directly into our bloodstream, we bypass the many defence mechanisms our bodies have for protecting us against harm, and so leaving us terribly exposed to the slightest manufacturing error or impurity within that medication.

And so, the public, patients and the medical profession need to be confident that:

  • the manufacturer produced the medicine to a high level of precision and safety and has taken every step to ensure this is the case.
  • no shortcuts have been taken in the manufacturing process or the sourcing of ingredients that could affect the strength, quality and purity of the final products

3) What are the Different Types of GMPs?

The United States, European Union, Japan, China, India, Korea, the UK, World Health Organisation (WHO), etc all have their versions of GMPs. There are other standards that aim to harmonise GMP requirements across countries and promote cross-recognition of standards across different regulatory jurisdictions such as the ICH (International Conference on Harmonisation) the PIC/S (Pharmaceutical Inspection Co-operation Scheme) organisation.

Many countries will often use one of the above sets of regulations rather than go to the expense of developing their own. The particular regulation the manufacturer will be subject to depends not only on the location of the manufacturing plant but especially on the location of the market the medicine or medical device will be supplied for patients. But the ultimate goal of GMPs is always to prevent harm to the end-user.

4) The Regulatory Authorities

In addition, each country has an organisation or agency that is responsible for the safety and efficacy (i.e it works) of the drugs that are manufactured and sold within its jurisdiction. The regulatory authorities will grant a license to a manufacturing plant to make a product based on that facility’s adherence to the relevant GMP regulations and enforce GMP regulations.

The regulatory authority may create its own GMP regulations and enforce them on any manufacturing plant supplying medicines to the public within its jurisdiction. For example, in the United States, the FDA (Food and Drug Administration) enforces its own 21 CFR Part 211 GMP regulations. The European Union has the EMA (European Medicines Association) which works together with the local regulatory authorities in each of its 27 member states who regulate their local manufacturers using the EU’s Eudralex regulations).

Even though the United Kingdom has left the EU, GMP regulations are still harmonized across Europe and UK manufacturers of medicines continue to work to the EU’s Eudralex regulations.

In addition, it’s common for a regulatory agency to audit and inspect a plant located outside its jurisdiction if that plant’s products are going to be supplied to the public within its jurisdiction. For example, there are a number of plants in Ireland, India and China which are inspected and audited by FDA inspectors as the products manufactured in those plants are going to be sold within the USA.

5) Cross Recognition of Regulation

In the not to distance past, it was not uncommon for a single manufacturing plant that was supplying product to different markets in Japan, Korea, the EU, USA, Canada etc, to be audited by the regulatory authorities from every single one of those countries. The plant would find itself in a state of being constantly audited. Needless to say, this was incredibly expensive and wasteful so to reduce the regulatory cost and burden, the regulatory agencies have been developing mutual cross-recognition agreements. So for example, if a plant in Japan is authorised by the PMDA (Pharmaceuticals and Medical Devices Agency), other regulatory agencies will recognise that authorisation removing the need for them to go an audit that factory and vice versa.

6) Licences and Authorisations

Once a new medicine has successfully completed its clinical trials, the relevant regulatory authority will grant it a “Marketing Authorisation or Product Licence”. This means that the medicine is approved for use.

In addition, the manufacturing plant where the medication is going to be made must have and maintain a “Manufacturing Authorisation” or “Manufacturing Licence”. To obtain this authorisation or licence or regulatory authorities must audit and approve the pharmaceutical plant where the medication is made.

7) People can’t be GMP certified. Nor can companies

Perhaps an often misunderstood point from people outside the industry is that technically speaking the pharmaceutical or medical device manufacturing company is not approved to make a specific medicine or product at all of its manufacturing plants. Instead, the regulatory authorities approve a specific product to be manufactured at a specific manufacturing plant. In other words, the local regulators (MHRA, FDA, etc) have visited, inspected and audited that facility and certified it to manufacture that product conditional on demonstrating strong regulatory commitment and compliance to the relevant GMP standards.

GMPs focus on the outcomes of the facility as a whole and not on the actions of one individual who was involved in its production. So the people or even the company aren’t certified. Only the manufacturing facility is certified to manufacture a specific product.

However, you may sometimes hear people say that a product is GMP Certified especially if they are from North America. What this means is that the product was made in a GMP-approved facility.

8) Regulatory Inspections

The regulatory authorities conduct routine and surprise inspections of sites that manufacture medicines making sure these are working to the principles of GMP and are in compliance. They check whether the manufacturing plants have the necessary facilities, equipment, and ability to manufacture the drug it intends to market.

If a company fails to comply with GMP regulations, it can result in severe consequences including, restriction, suspension or forfeiture of rights to continue manufacturing the goods, product recall, seizure of the goods, fines, and even jail time.

These inspections are typically conducted every two or three years and if the inspections do not go well, the site could be put under warning or even closed. More frequent inspections will occur if the authorities have any concerns.

9) What is the difference between GMP and cGMP?

cGMP stands for “Current Good Manufacturing Practices”. The Food and Drug Administration (FDA) in the USA wanted to remind drug manufacturers of the need for continuous improvement in their approach to product quality.

The FDA warned against a “set and forget” approach to compliance with the GMP guidelines, and wanted manufacturers to make sure that product quality became a core focus within their organisations. Systems and equipment used to make products that may have been outstanding 20 years ago may be far from adequate by current standards.

Most countries don’t use the ‘c’ for ‘current’ as it’s assumed that manufacturers will keep up to date with changes to the GMP guidelines and will strive to meet them. And so for most practical purposes the terms cGMP and GMP are largely interchangeable terms.

10) What are GxPs?

GxPs is an umbrella term for several “Good Practice” frameworks which includes “GMPs”. These frameworks were created to make sure that high levels of quality and safety are built into every step from drug development and manufacture to distribution and storage as we don’t just want only the manufacturing process to be safe. We need these other steps and processes to be safe as well.

These include:

  • Per Clinical Development: Good Laboratory Practice (GLP)
  • Drug trials: Good Clinical Practice (GCP)
  • Manufacturer: Good Manufacturing Practice (GMP)
  • Distribution: Good Distribution Practice (GDP)
  • Storage: Good Storage Practice (GSP)

And collectively, all these standards are known as GxPs.

Good Manufacturing Practices vs GxPs

Lifecycle overview showing where GxP and GMP is implemented.

11) What is a Quality Management System and how does it fit together with GMPs?

A quality management system documents a company’s processes, procedures, and responsibilities to help it provide a quality product or service. It helps coordinate and direct an organisation’s activities to meet customer and regulatory requirements.

Arguably the most recognised and widely implemented quality management system is the ISO 9001 standard. This standard is published by the ISO organisation based in Switzerland and provides a set of requirements for an organisation regardless of what it does or its size. It’s a tried and tested framework for managing the organisation’s processes so that they consistently turn out products that satisfy customers’ expectations.

A company that uses ISO 9001 can have itself audited by the ISO organisation and publicly state that it is “ISO 9001 Certified” or “ISO 9001 Registered”. However, certification to the ISO 9001 standard does not guarantee compliance with GMPs (and therefore the quality) of end products and services. Rather, it certifies that consistent business processes are being applied. That is all.

12) How does ISO 9001 compare with GMPs?

While GMP regulations and ISO standards are often compared, the two are not the same and are not really trying to do the same thing.

Think of GMPs as regulations and legal requirements that pharmaceutical manufacturers must comply with. Think of the implementation of a quality management system such as ISO 9001 as a framework you can use to achieve compliance with those regulations and legal requirements

GMP is a product quality regulation that has the force of law behind it. Its focus is on getting product efficacy, (i.e it works) and manufactured to a high-quality standard for the most important customer of GMPs – the patient. If your manufacturing facility doesn’t strictly follow GMPs, the local regulatory authority can compel the plant to make changes, recall products, or even halt production.

ISO 9001 is a tried and tested quality management system that is regularly used by pharmaceutical manufacturers to help meet its GMP regulatory requirements. ISO 9001 is also more about running the whole business, a goal of which will be producing products of the right quality – but it has other aims too. Whilst GMP focuses on regulating production and quality control – ISO 9001 focuses on all departments and processes of an organisation.

13) Do all the ingredients and materials that go into a finished drug product need to be manufactured under the control of GMPs?

Yes. However, the GMPs for excipient fillers in a tablet, are different to the GMPs for the APIs (Active Pharmaceutical Ingredients) in the same tablet, which are different to the GMPs for active ingredients in an injectable.

These in turn are different to Water for Injection (WFI) which is added to the same injectable, which are different to the GMPs for the blister pack materials or vials in which they are packaged for distribution to the patients, which are different to the GMP’s governing the product instructions for the patient who will be taking the medicine that are included in the packaging box.

14) How do I get started using GMPs within a manufacturing plant?

There is a vast difference i