As quality professionals, we know that a vital part of keeping patients safe is making sure that drug products are manufactured consistently and that the end products are of high quality. This is pretty much taken for granted by the public today, but back in 1962—in response to a series of hazardous drugs that caused widespread harm to patients—the need for better patient protection was clear.
That’s where Current Good Manufacturing Practice (cGMP) regulations for drugs came in—also known as FDA CFR part 210 and part 211. Together, these regulations provided a framework for the safe production and distribution of standardized, high-quality drugs in the US.
In this post, we’ll focus on 21 CFR part 210. We’ll explain why 21 CFR part 210 is important, describe best practices for staying 21 CFR part 210-compliant, and provide five common pitfalls to avoid if you’re new to the compliance game.
Protecting drug standards with FDA 21 CFR parts 210 and 211
Thanks to 21 CFR part 210 and part 211, patients are kept safe, healthcare providers can prescribe with confidence, and payers can rest easy knowing that products will deliver consistent value.
How? Any drug company that wants to market products in the US must comply with the minimum and most up-to-date standards set out in 21 CFR part 210 and part 211. These standards apply to manufacturing methods, facilities, controls, and the processing, packing, and storage of drugs and are enforced by the FDA.
What’s the difference between 21 CFR part 210 and part 211?
For quality teams, it’s important to understand the regulations we need to follow. While 21 CFR part 210 is an overarching regulatory framework and is relatively short and sweet, part 211 is much longer, filling in many details of the framework, setting out the specifics of cGMP for drugs and quality control (QC) processes, facilities, equipment, personnel, and much more.
Get the full breakdown of complex GMP requirements and expert tips for ensuring compliance in our handbook!
Key FDA 21 CFR Part 210 guidance and requirements
So, what’s covered by 21 CFR part 210? There are three parts to bear in mind: the status of cGMP for drugs, its applicability, and a list of definitions of key terms. Let’s dive into each.
1. The ‘status’ of cGMP (i.e., 21 CFR 210.1) defines the purpose, scope, and consequences of noncompliance
Purpose:
As I already mentioned, the purpose of cGMP—or FDA 21 CFR part 210—is to ensure the safety and quality standards of drugs during manufacturing and distribution in the US. To quote the regulations directly, the purpose of cGMP is to ensure that a drug:
“…meets the requirements of the act as to safety, and has the identity and strength and meets the quality and purity characteristics that it purports or is represented to possess.” [FDA 21 CFR 210.1]
We can understand pretty clearly from this statement that drugs have to contain the substances they claim at the strength, quality, and purity described by the manufacturer.
Scope:
The scope of cGMP is wide-ranging so that every aspect of drug manufacturing, processing, packing, and storage is covered. This includes not only the methods being used but also the facilities and QC processes. To quote the regulations directly, the cGMP encompasses:
“…the minimum current good manufacturing practice for methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing, or holding of a drug…” [FDA 21 CFR 210.1]
Staying current:
It’s clear that FDA 21 CFR part 210 regulations focus on staying up-to-date, or “current,” with good manufacturing practices. This is what sets cGMP apart from GMP—a set of less stringent minimum manufacturing practices that don’t always incorporate the newest methods or technologies.
While both GMP and cGMP aim to produce high-quality products, cGMP incorporates the most advanced regulations and standards available. By following cGMP, manufacturers can keep up with industry advancements and consistently improve their drug quality.
Noncompliance:
Drugmakers that don’t comply with any of the regulations in cGMP, whether those of 21 CFR part 210 or part 211, “render the drug to be adulterated,” which can have devastating consequences. It’s important to remember that the drug, as well as the person responsible for noncompliance, are subject to regulatory action.
Aside from reputational damage, the affected product is recalled, business can be lost, fines may be issued, and there could even be a complete shutdown of operations
2. The ‘applicability’ of cGMP (FDA 21 CFR 210.2) defines which drugs are covered and which are exempt
Applicability:
The regulations in 21 CFR part 210 apply to every organization in the United States that takes part in the production and distribution of drugs, whether that’s prescription or over-the-counter drugs, and even applies to active ingredients as well as finished dosages.
Biological and HCT/P products:
Certain kinds of products might also be subject to additional regulations. These include biological products and human cell, tissue, or cellular- or tissue-based products (HCT/P). In each case, regulations supplement rather than supersede each other, meaning that all regulations still apply, including those of 21 CFR part 210. However, when there’s a conflict between regulations, the regulation that specifically applies to the product in question takes precedence.
Products in development:
FDA 21 CFR part 210.3 explains that Investigational New Drugs still in clinical development are treated like finished pharmaceutical products once the drug has reached phase 2 or further and must then comply with 21 CFR part 211, which covers finished pharmaceuticals.
3. ‘Definitions’ of cGMP (21 CFR 210.3) provide a standard lexicon
A list of terms, along with their definitions, is provided so that manufacturers can clearly understand the regulations without room for interpretation.
For example:
- “Batch means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.
- Quality control unit means any person or organizational element designated by the firm to be responsible for the duties relating to QC.
- Representative sample means a sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled.” [FDA 21 CFR 210.3]
See Part 210.3 for a full list of definitions.
Best practices for complying with 21 CFR part 210
Monitor regulatory changes
For quality teams in life sciences, staying up to date with the latest regulatory requirements is vital. Organizations should actively monitor the FDA and other regulators to make sure they keep up with any changes.
Establish a robust quality management system
It can be a daunting task to set up a compliant quality control system. That’s why building a robust quality management system (QMS) is so essential. A reliable and efficient QMS should check and guarantee manufacturing processes as well as the end products (i.e., the drugs), establish standard operating procedures (SOPs) for critical activities, document control procedures, and change management for suppliers, personnel training, and quality monitoring.
Advanced tools
In addition to using modern manufacturing equipment and facilities, organizations should consider how the tools and processes they adopt—such as a digital QMS—can help create an efficient quality management infrastructure.
Comprehensive personnel training
It's easy to overlook personnel knowledge and education, but this is a crucial part of 21 CFR part 210 compliance. All personnel involved in the manufacturing, processing, packing, and holding of drugs should receive comprehensive and continuous training specific to each role. That way, they can understand part 210’s definitions and apply its regulations in a uniform way. A good place to start is by assessing current knowledge gaps. Regular refreshers and evaluations can reinforce knowledge and highlight gaps for further training.
Conduct regular audits
By conducting regular internal audits, organizations can spot gaps and problem areas before regulatory authorities do and take corrective actions. Third parties can also provide an independent source of feedback. Audits should be well-documented, objective and have enough resources allocated toward them to ensure they are thorough and meet regulatory standards.
Common pitfalls of cGMP compliance
According to the FDA’s own figures, cGMP compliance warnings to drug companies have skyrocketed recently with the number of compliance warnings issued by the FDA following inspection more than doubling in the past three years.
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Absence of written procedures or procedures not fully followed:
By far, the most common compliance issue for pharma in 2024 was incomplete paperwork with “procedures not in writing or fully followed” or an “absence of written procedures” accounting for 327 (58%) of the 561 warnings issued by the FDA in 2024.
Other common pitfalls in the same year included:
Failure to properly investigate discrepancies, or failure by the QC function within the organization, which is tasked with thorough investigation and reporting following a discrepancy or failure, to take appropriate follow-up actions. This was responsible for 134 (24%) of the 561 warnings issued in 2024.
A lack of scientifically sound laboratory controls to provide accurate and reliable data—crucial for monitoring and testing—accounted for 119 (21%) of the 561 warnings issued.
Improper equipment maintenance, design, size, and location, including the cleaning and sanitizing of equipment, was responsible for 85 (15%) of the warnings issued.
Inappropriate computer control of master formula records comprised 60 (15%) of the warnings issued. This is likely to be the result of documents that were stored where unauthorized personnel could access them.
Key takeaways
- Current Good Manufacturing Practices (cGMP) regulations apply to all US organizations involved in drug production and distribution, including both prescription and over-the-counter drugs. These standards are detailed in the Food and Drug Administration (FDA) Code of Federal Regulation Title 21 (21 CFR) parts 210 and 211, which together provide a framework of good, up-to-date manufacturing and distribution practices.
- FDA 21 CFR part 210 is short compared with 21 CFR part 211 and covers the status and applicability of and important definitions associated with cGMP regulations (whereas part 211 contains many more details about the requirements).
- A robust quality management system is crucial for compliance, establishing standard operating procedures (SOPs) for critical activities, document control, and change management.
- Comprehensive and continuous training for all personnel involved in drug manufacturing is essential to understand and apply 21 CFR part 210 regulations uniformly.
- Regular internal and third-party audits help identify and rectify gaps before regulatory authorities do.
- cGMP compliance warnings have increased dramatically in recent years, with the absence of or failure to follow written procedures accounting for over half of FDA warnings in 2024.
Ensuring compliance with 21 CFR Part 210 compliance
With rising regulatory scrutiny, one thing is certain: pharmaceutical organizations must take a proactive approach to the way they manage their QMS. This is where Scilife, a trusted expert in the life sciences, can help. From streamlining complex, paper-based systems with our smart QMS software to fostering a strong quality culture, we empower organizations to implement industry best practices and avoid common compliance pitfalls.
