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Why incorporating GMP and USP is best practice for early phase trials

Patient safety and data integrity are the primary concerns in early phase clinical trials. In the US sponsors generally follow one of two standards sets when conducting early phase trials: Good Manufacturing Practice (GMP) or United States Pharmacopeia (USP). In this article we look at each practice set and weigh their relative advantages and disadvantages. We’ll explore why incorporating both is now considered best practice for early phase trials.

What is GMP?

GMP is a set of regulatory guidelines to ensure that pharmaceutical products including drugs, biologics and active pharmaceutical ingredients, are manufactured consistently and under controlled conditions. It is designed to guarantee products are produced, processed and controlled according to stringent quality standards to ensure patient safety, product efficacy and regulatory compliance. Compliance with these standards is mandatory under federal law and non-compliance risks trial suspension and regulatory setbacks. For early phase studies the FDA allows some flexibility but still requires documentation and control. 

What is USP?

United States Pharmacopeia (USP) is a non-profit scientific organisation that develops and publishes the official standards for medicines, food ingredients and dietary supplements in the US. Its role in pharmaceutical compounding is critical, setting public standards for quality, purity, strength and consistency of compounded medications. USP is recognised by the FDA as the official source of quality standards for drugs and drug ingredients in the US. The standards set by USP are widely recognised and often enforceable by FDA and state regulations. 

Differences between GMP and USP

Both GMP and USP aim to set high standards of practice for the pharmaceutical manufacturing, but they have key differences. The table below outlines how some aspects differ. 

AspectGMPUSP
Regulation

Mandated by 

FDA 21 CFR Parts 210/211

cGMP for phase 1 investigational drugs

Regulated by 

State boards of Pharmacy

DocumentationExtensive batch records, CAPA, deviations, risk assessments, etc

Minimal documentation

(preparation worksheets, no batch records)

Quality systems

Formal Quality Management System is required

(QMS)

Often no formal QMS or QA oversight is required
Validation requirements

Required 

(process, equipment, method validation)

Not required
TraceabilityHigh level of traceability and auditabilityLimited or no traceability for small-scale preparations
Suitability

Ideal for clinical trials and 

suitable for up-scale production

Suitable for personalised compounding in hospitals or pharmacy settings

Quality Control 

Laboratory

Mandatory

As needed

(e.g., extended BUD/Stability)

Better together: Why early phase trials should incorporate both GMP & USP

If USP guidelines are the foundation for safe and effective compounding, incorporating them with GMP standards ensures strong walls are built on that foundation. A hybrid approach of USP and GMP for phase 1 trials is increasingly seen as best practice during early phase development. USP compounding alone does not offer guarantees, which can potentially endanger patient safety and trial data validity. GMP offers validated processes, extensive documentation, traceability and robust quality systems. These elements guarantee every batch of investigational drug is consistent, auditable and manufactured to uncompromising standards. Incorporating USP practices within GMP frameworks give sponsors the best of both practice sets. This allows sponsors to maintain flexibility and cost-effectiveness while also fulfilling regulatory expectations and protecting trial integrity. 

Early phase trials often include first‑in‑human (FIH) studies, where patient safety relies heavily on the consistency and reproducibility of investigational drug materials. GMP compliance ensures that manufacturing processes for investigational drug materials are controlled and documented to meet regulatory quality standards. Aside from the advantages of GMP compliance already outlined, it has the benefit of meeting regulatory requirements outside of the US. Data and documentation created under GMP can often be leveraged for submissions in multiple regions and meets EMA expectations for investigational drugs. This can streamline future approvals, miminise duplication of effort, and provide safety and risk mitigation. 

What happens when best practices are not implemented?

The concept of patient safety can seem abstract within the confines of a laboratory. But the consequences of not following best practices can have very real, sometimes tragic, outcomes. One high profile case was the New England Compounding Center meningitis outbreak in 2012. The contaminated product was administered to an estimated 14,000 people. Almost 800 people in at least 23 states were infected with fungal meningitis and more than 100 people died.1 The tragedy led to multiple civil, state, and federal lawsuits and ultimately the criminal convictions of the laboratory owner and four employees. Prompted by this case, in 2013 the Drug Quality and Security Act granted the FDA stronger oversight to regulate pharmaceutical institutions. This contributed to enhanced product safety and heightened awareness and attention to the manufacturing process.

Even with increased oversight, lapses in quality can occur. In 2025 the FDA and EMA discovered elevated levels of nitrosamines, a probable human carcinogen, in certain batches of blood pressure drugs. A voluntary recall of 580,000 bottles of the treatment was issued.2 The exposure was estimated to be relatively low due to the limited number of days the drugs were in circulation (167 days in the US and 146 in Canada). Proper assessment and control during manufacturing and monitoring and testing of the finished product are essential to mitigate the risk of nitrosamine impurities above acceptable levels. 

As William Edwards Dening observed, “Quality cannot be tested into products; it must be built in.” Working with a CRO that follows both GMP and USP best practices in early phases of trials gives early phase sponsors the advantages of both. For sponsors it eliminates costly regulatory setbacks, streamlining the regulatory process in new territories; for patients it is simply life-saving. 

References

  1. Multistate Outbreak of Fungal Meningitis and Other Infections – Case Count. Centers for Disease Control and Prevention. https://archive.cdc.gov/#/details?url=https://www.cdc.gov/hai/outbreaks/meningitis-map-large.html. Published 2015. Updated 30 October 2015. Accessed 9 January, 2026.
  2. Gerlach A. FDA Announces Recall 580,000 Bottles of Prazosin Over Potential Carcinogenic Impurity | Pharmacy Times. Published 2025. Accessed 9 January, 2026.
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