What is GMP?

Let’s begin by clarifying that GMP stands for Good Manufacturing Practice. It defines the minimum standards to be followed during the manufacture, testing, and distribution of medicinal products to ensure that medicines are consistently produced and controlled to the quality standards appropriate to their intended use, in compliance with the requirements of the marketing authorization or clinical trial authorization and are safe for patients. In addition to pharmaceuticals, GMP principles are also applied to varying degrees, to active pharmaceutical ingredients (APIs), dietary supplements, cosmetics, and medical devices.

Legal Requirements

The origins of GMP can be traced back to the U.S. Federal Food, Drug, and Cosmetic Act, signed by President Roosevelt in 1938. The act was enacted following the 1937 Elixir Sulfanilamide tragedy, where the product contained toxic diethylene glycol (not declared on the label), resulting in the deaths of 107 people – mostly children.

The Act introduced, among other provisions, the requirement to demonstrate the safety of new drugs before marketing, enhanced regulatory control, standards for identity and quality, and official factory inspections [1]. This marked a major step toward the modern GMP framework, the compliance of which is now monitored by national regulatory authorities (see Table 1). [2,3,4]

Tab. 1 Main GMP Regulatory Frameworks

Country/Region	Authority	Key Regulations
European Union	European Commission	EudraLex Volume 4 – Good Manufacturing Practice (GMP) Guidelines
Poland	Ministry of Health	Regulations of the Minister of Health on Good Manufacturing Practice
USA	Food and Drug Administration (FDA)	21 CFR Parts 210 and 211

General GMP Requirements

One might ask – why do we need GMP if we already have quality control (QC)? Indeed, until the late 1970s, QC testing was considered the main safeguard of drug safety and efficacy. However, QC testing is based on sampling, which should be representative of the whole batch, and yet certain defects – such as contamination, packaging mix-ups, or loss of sterility – may not be uniformly distributed across a batch and thus can easily go undetected during QC testing.

There are numerous GMP requirements, and Table 2 presents a selection of ten key ones.

No.	Key GMP Requirements
1	A Quality Assurance system must be implemented in pharmaceutical manufacturing.
2	All processes must be documented at the time they are performed.
3	Critical manufacturing steps must be validated.
4	Premises and equipment must be properly designed, qualified, and maintained.
5	Computerized systems must be validated.
6	Personnel must be competent and adequately trained.
7	Products must be protected against contamination and mix-ups.
8	A hygiene program must be established and implemented.
9	Internal audits must be conducted.
10	Complaints and product recalls must be recorded, investigated, and managed appropriately.

Consequences of Non-Compliance with GMP

Failure to comply with GMP – despite increasingly strict regulations – continues to pose risks to patient health and life. Below are several examples.

2023 – United Kingdom, Australia – Legency Remedies

Issue: Contamination of 0.9% sodium chloride solutions manufactured by Indian producer Legency Remedies with Ralstonia pickettii bacteria. [5]

Consequences: Three confirmed cases of bloodstream infection in immunocompromised patients were reported in the UK, and in Australia 43 suspected cases and one death of an elderly patient infected with the same bacteria. Product batches manufactured between April and November 2023 were recalled in both countries.

Root Causes: Presence of Ralstonia pickettii in water systems or filling lines, lack of effective microbiological monitoring, inadequate root cause investigation, and ineffective corrective and preventive actions (CAPA) following out-of-limit results.

2020 – India – Digital Vision Pharmaceuticals

Issue: Approximately 35% concentration of toxic diethylene glycol found in Coldbest-PC cough syrup for children. [6]

Consequences: More than nine children in northern India died from acute renal failure caused by diethylene glycol poisoning.

Root Causes: Contamination of the raw material (propylene glycol). Systemic GMP failures included poor supplier qualification, lack of adequate raw material release testing, missing impurity checks, unvalidated processes, and insufficient manufacturing oversight.

2020 – USA – Luminex Corporation

Issue: Diagnostic medical device malfunctioned, resulting in a missed Pseudomonas infection diagnosis. [7]

Consequences: Antibiotic treatment was delayed by several days until the correct diagnosis was made; unfortunately, the patient died two days later.

Root Causes: Lack of process validation after changes and deviations, ineffective CAPA, inadequate oversight of maintenance activities, and failure to implement an effective product recall system.

2018 – Global – Nitrosamine Contamination (Various Manufacturers)

Issue: In 2018, N-nitrosodimethylamine (NDMA) contamination was detected during QC testing by Prinston Pharmaceuticals Inc., a U.S. manufacturer of valsartan, which notified the FDA and suspended production due to the carcinogenic nature of NDMA. [8]

Consequences: Over 1,200 product batches were recalled in the United States alone, with similar recalls across the European Union and other regions.

Root Causes: Insufficient oversight of API suppliers, poor change control in API manufacturing processes, and inadequate process validation.

Summary

GMP—Good Manufacturing Practice—defines the regulatory framework for manufacturers of medicinal products and other health-related goods. Its primary purpose is to ensure that medicines are consistently produced to a standard of quality suitable for patient safety and intended use.

Compliance with GMP is supervised by national regulatory authorities and must be fully integrated into a company’s Quality Management System. Adherence to GMP is one of the core pillars of the pharmaceutical industry. Non-compliance, however, can have devastating consequences for patients and catastrophic business impacts.

The competence and ethical commitment of employees—and especially of pharmaceutical industry leaders—are fundamental to patient safety and the long-term success of any organization manufacturing medicines: exceptional products that every one of us relies on.

References

Andrzej Szarmanski
Pharma GMP
www.pharma-gmp.com

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