What Is the Difference Between Laboratory, GLP, and GMP Steam Sterilizers?

“What is the difference between a GMP and a non-GMP autoclave?”

It’s a question our sales and engineering teams hear often. Many of our clients mistakenly believe Good Manufacturing Practice (GMP) requirements are universal to all steam sterilizers used in pharmaceutical or biotechnology facilities. As a result, they assume these requirements apply to applications that actually fall outside the GMP umbrella.

In this blog post, we’ll explain the difference between GMP vs. GLP (and other non-GMP) sterilizers, and when you should use one or the other.

What Is GMP?

GMP, short for Good Manufacturing Practice, refers to a collection of quality assurance regulations. Also referred to as current Good Manufacturing Practice (cGMP), these regulations ensure products in various industries, including food and beverage, pharmaceuticals, cosmetics, and medical devices, meet specified quality, safety, and efficacy standards. GMP regulations also ensure the processes used to manufacture these products are reproducible.

While there are many different GMP regulations, each with their own unique specifications, almost all require manufacturers to:

• Maintain a controlled environment to prevent cross-contamination
• Clearly define and control all critical processes
• Evaluate and validate any changes to critical processes
• Comprehensively document all instructions and procedures
• Train operators to carry out and document procedures
• Maintain detailed records of all manufacturing processes to ensure adherence to defined procedures
• Investigate and document any deviations from defined procedures
• Maintain detailed records of all distribution processes to ensure batch traceability
• Implement a quality management system (QMS) to centralize documentation and manage batch recalls
• Examine customer complaints and investigate the cause of any quality defects
• Take appropriate measures with respect to defective products and prevent recurrence

Examples of GMP regulations implemented and enforced by the U.S. Food and Drug Administration (FDA) include:

• 21 CFR Part 314 explains how drug companies must apply to the FDA for permission to sell a new prescription drug.
• 21 CFR Part 210 establishes basic rules for how medicines must be made, setting general standards for cleanliness, equipment, and processes inside drug manufacturing facilities.
• 21 CFR Part 211 sets forth rules for manufacturing finished medicines, with requirements for labeling, packaging, quality control, and storage.
• 21 CFR Part 212 establishes rules for Positron Emission Topography (PET) drugs, which are special radioactive medicines used in imaging tests.
• 21 CFR Part 600 stipulates what rules manufacturers must follow to ensure biological products, such as vaccines, blood products, and certain therapeutic proteins, are safe, pure, and effective before they’re used on patients.

Beyond the FDA, there are many other global frameworks responsible for implementing and enforcing GMP regulations. These include:

• The World Health Organization (WHO), which publishes GMP guidelines for global use and performs prequalification inspections for medicines
• The International Council for Harmonisation (ICH), which creates harmonized technical guidelines that are used globally. While the ICH is not an enforcement body, its quality guidelines influence GMP expectations.
• The Pharmaceutical Inspection Co-operation Scheme (PIC/S), a global partnership of regulatory agencies that share inspection standards and work to harmonize GMP expectations across countries
• The European Medicines Agency (EMA), which harmonizes GMP practices across the European Union through the EudraLex Volume 4
• Health Canada, which establishes and enforces GMP through its own set of PIC/S-aligned regulations
• The Pharmaceuticals and Medical Devices Agency (PMDA), the Japanese government agency responsible for enforcing Japan’s GMP requirements, which align with ICH and PIC/S standards
• The Therapeutic Goods Administration (TGA), the Australian government agency responsible for evaluating, assessing, and monitoring products that are defined as therapeutic goods and regulating medicines, medical devices, and biologicals

GMP Documentation & Records

The entire purpose of GMP is to ensure products are consistently produced and controlled according to high-quality standards. This requires having a clear, structured approach to documentation and record-keeping to maintain traceability and accountability. Here, we’ll take a closer look at the differences between key documentation types and how they work together.

Protocols vs. SOPS

Standard operating procedures (SOPs) are among the most critical documents in GMP. They describe the standardized way in which activities should be performed within a facility to ensure consistency and quality. As such, SOPs provide detailed instructions on routine tasks such as cleaning equipment, calibrating instruments, and handling raw materials to ensure that every person in the facility follows the exact same procedures, reducing the risk of human error.

Protocols, on the other hand, are typically created for specific, one-time activities and outline how a particular process will be executed and controlled. For example, if a facility were to validate a new process or piece of equipment, it would create a protocol to define how it will be done, the criteria for success, and the methods for recording data.

Batch Records: MBR vs. BPR

Batch records are crucial for documenting the actual manufacturing process for a product, providing a complete record of everything that happened during the production of a specific batch of that product.

A master batch record (MBR) is a template that outlines how every draft should be produced. It is a standardized document that includes all the necessary details about the materials, procedures, and equipment required to make the product. In addition to defining step-by-step instructions for manufacturing, it also outlines tests to be performed, in-process controls, and the specifications the product must meet.

Once manufacturing begins, the actual process is documented in a batch production record (BPR). A BPR is a real-time log of what happened during production and includes the actual values, measurements, and observations made during the manufacturing process. The BPR is essentially the completed version of the MBR, documenting whether the product was made according to the prescribed plan. A BPR also includes signatures of the operators, supervisors, and other relevant personnel to confirm the batch was made properly.

Data, Records & Reports

GMP documentation often starts as raw data — unprocessed information collected during manufacturing or testing. This can include things such as lab results, weight measurements, temperature readings taken during production, and so on. This raw data serves as the foundation for further analysis and decision making.

Records are organized versions of raw data. They’re structured logs or forms in which raw data is captured, often after being verified for accuracy. For example, a laboratory test might produce raw data in the form of instrument readings; those readings would then be recorded in a formal log, providing a permanent, legible record of what was observed.

Reports are documents that interpret the raw data found in records. They analyze the information gathered, summarize findings, and often provide conclusions. For example, an investigation report might analyze data from a batch record to determine the cause of an out-of-specification result.

Retention Periods for GMP Documents

Under GMP, documentation must be retained for specific periods in the interest of traceability, accountability, and the ability to verify that a product was made according to standard.

These retention periods vary by region and regulation. For example, according to 21 CFR Part 211 Subpart J, the FDA requires facilities to retain batch production records, quality control test results, and other critical documents for finished drug products for at least one year after the expiration date of the product. This retention period guarantees that if a product issue arises post-market, the manufacturer can refer back to the records and trace the production process.

Retaining records for the specified period is essential to audits, inspections, or investigations into product quality and supports ongoing quality assurance efforts so products meet regulatory standards long after they leave the production facility.

Corrective and Preventative Action

Corrective and Preventative Action (CAPA), a cornerstone of GMP compliance, is the process by which a company identifies, investigates, and corrects quality problems that have already occurred and implements measures to prevent similar problems from occurring in the future.

When a deviation, out-of-specification result, or quality complaint occurs, a company must initiate a CAPA investigation. This process entails several steps:

1. Identify and record the issue, providing a detailed description of what happened and supplying any supporting evidence.
2. Evaluate the severity and scope of the issue, noting its potential impact on product quality and safety.
3. Conduct a thorough investigation to identify the root cause of the issue.
4. Analyze findings to confirm the root cause of the issue, documenting all findings.
5. Develop an action plan to resolve the current issue (corrective action) and prevent recurrence (preventative action).
6. Implement both corrective and preventative actions, coordinating across departments.
7. Verify the efficacy of both the corrective and preventative actions, monitoring long-term to ensure improvement.
8. Make any necessary adjustments to the CAPA plan.

All GMP regulations mandate CAPA in the interest of continuous improvement, product safety, and quality assurance.

What Is a GMP Sterilizer?

A GMP sterilizer or autoclave is a specialized piece of equipment used in the pharmaceutical, biotechnology, and other regulated industries to sterilize products, equipment, or materials through the use of steam and pressure. Any product used in the testing or manufacturing of human-use drug products, or in the terminal sterilization of the drug itself, must be performed in a GMP autoclave. GMP sterilizers must therefore adhere to a set of stringent requirements that range from approved construction materials to the purity of the water that can be fed to the sterilizer.

Some general notes about GMP sterilizers:

• Water source: Must be fed with high-purity water (>1 Megaohm sourced from WFI); steam quality must be verified for dryness, superheat, and impurities.
• Sterilizer plumbing: All piping must be constructed from medical-grade stainless steel, clamped and orbital welded.
• Temperature monitoring: Temperature monitoring and control must be independent and require redundant control systems.
• Chamber finish: Chamber must be polished to a mirror finish (<10Ra).
• Filtration: All air must be vented through sterilized-in-place microbial filters with dedicated steam lines.
• Validation documentation: Documented quality control validation and checkoff required for each stage of installation and sterilization (installation qualification, operational qualification, performance qualification).
• Sterilizer control system: Controls comply with 21 CFR Part 21 standards for data security.

Common Sterilization Cycles in GMP Labs

GMP sterilizers are capable of running a wide range of cycles, each designed for a distinct purpose; some of these include:

• Gravity cycle: The most common steam sterilization cycle, a gravity cycle pushes steam into a chamber containing ambient air. Through a process known as displacement, steam fills the chamber, forcing the air out through a drain vent and penetrating the load. Gravity cycles are often used to sterilize glassware, unwrapped goods, waste, utensils, and red bags.
• Pre-vacuum cycle: A pre-vacuum mechanically removes air from the chamber and the load through a series of vacuum and pressure pulses. This enables steam to penetrate porous areas of the load it wouldn’t otherwise be able to reach through simple gravity displacement. Pre-vacuum cycles are ideal for wrapped goods, packs, animal cage bedding, cages, porous materials, and redbags.
• Liquid cycle: As its name implies, a liquids cycle is specially designed for liquid loads. Unlike gravity or vacuum cycles, which can cause lysogeny broth, media, agar, saline, water, and other liquids to boil over, a liquids cycle releases pressure from the autoclave chamber more slowly during the exhaust phase, thereby allowing the liquid load to cool off.
• Steam-air mix: A steam-air mix cycle is a specialized cycle designed to sterilize sealed, pressure-sensitive items by injecting compressed air into the autoclave chamber during the sterilization phase to artificially raise the pressure. Even after the sterilization phase is complete, the autoclave will maintain an elevated chamber pressure during the exhaust phase, which it will slowly reduce as the temperature falls, maintaining the integrity of the load.

For a comprehensive review of all sterilization cycles and guidance on which ones to use when, check out our complete library of sterilization cycle guides.

What Is GLP?

Good Laboratory Practice (GLP) is a quality system designed to ensure the quality, consistency, and reliability of non-clinical laboratory studies. These studies are typically conducted to assess the safety and efficacy of chemicals, drugs, and other products, typically before they enter clinical trials or the market. GLP is essential to generating reliable data that facilities can submit to regulatory agencies, such as the FDA, the U.S. Environmental Protection Agency (EPA), and the EMA, to support product approval and safety assessment.

Though there are variations in GLP requirements, the general principles that ensure laboratory research is conducted systematically and produces trustworthy, reproducible results are:

• Establish and maintain a clear organizational structure with defined roles and responsibilities for all laboratory personnel
• Develop comprehensive study plans that outline the objectives, methodologies, and procedures for each study
• Implement strict quality assurance practices, including independent QA units that regularly audit studies and confirm compliance with GLP standards
• Use validated and calibrated equipment to ensure all instruments used in studies meet the required standards
• Adopt and follow SOPs for all critical operations, including defining all methods for testing, sample handling, and data collection
• Verify proper handling and documentation of test systems so that study subjects are properly identified, maintained, and monitored
• Accurately record and archive all data in a secure, accessible location
• Prepare detailed final reports that summarize the methods, results, and conclusions of the study
• Monitor and maintain laboratory environment to prevent contamination
• Review and address deviations from the study plan or SOPs, including thorough investigations into any discrepancies, and take corrective actions to prevent future occurrences
• Train all personnel to carry out their assigned tasks, maintaining detailed records of training activities and qualifications

The FDA also has GLP regulation, 21 CFR Part 58, which establishes requirements for conducting and reporting nonclinical studies, so that all laboratory activities related to product safety testing meet consistent standards. This regulation applies to preclinical testing for pharmaceuticals, biologics, and chemicals, ensuring the integrity of data submitted to regulatory authorities for product approval.

Outside the U.S., the Organisation for Economic Co-operation and Development (OECD) is the primary body responsible for maintaining and enforcing GLP standards. The OECD’s GLP guidelines are widely adopted by member countries and other international organizations to create uniformity and consistency in laboratory testing.

GLP Documentation & Records

Similar to GMP, GLP emphasizes the importance of maintaining clear, accurate, and traceable records to ensure the integrity of the study or production process. Those records include:

• SOPs: GLP requires SOPs for laboratory activities such as sample collection, equipment calibration, testing methods, and data recording in the interest of confirming that each step of the study is performed consistently and correctly. Any deviation from these SOPs must be documented, and the reason for the deviation explained.
• Study protocols: Laboratories must develop a study protocol (or study plan) prior to the commencement of any non-clinical study. This study protocol outlines objectives, methodologies, and detailed procedures for conducting the research, including the test substances, controls, and criteria for evaluating results. All changes to the study must be documented, with clear justification for why those changes were made.
• Final study reports: Once a study is complete, those performing it must prepare a final report that summarizes the study’s objectives, methods, results, and conclusions. The report should be based on the documented data, including raw data, analysis, and interpretations, and be clearly written and supported by documented evidence.

Again, like GMP, the retention period for GLP records varies by regulation. The FDA, for example, stipulates under 21 CFR 58.195 that laboratories must retain GLP records for a period of at least five years following the date on which the results of the non-clinical laboratory study were submitted to the FDA. All GLP regulations mandate that these records be kept in a legible, permanent, and traceable format for reproducibility.

What Is a GLP Sterilizer?

A GLP sterilizer refers to a steam sterilizer used in GLP environments to sterilize laboratory tools, materials, and equipment as part of the required procedures for maintaining a sterile, contamination-free environment. While GMP autoclaves are intended for manufacturing, GLP autoclaves preserve the accuracy, integrity, and reproducibility of laboratory data.

This secondary designation loosens some of the GMP regulatory requirements for pre-clinical trials. A GLP sterilizer is a good option for facilities that know their research will eventually lead to clinical trials and want an autoclave they can use from the exploratory stage through the pre-clinical stage without the continuous regulatory oversight of GMP. A GLP sterilizer can be a lower-cost alternative that only needs to be replaced when the lab needs to ramp up to a production/clinical trial footing.

Due to the lowered requirements, most laboratory sterilizer manufacturers can meet GLP standards (listed below) with the correct combination of optional features:

• Water source: Must be fed with high-purity water (>1 Megaohm), requiring secondary filtration equipment and storage tanks
• Sterilizer plumbing: All piping must be constructed from medical grade stainless steel but may be National Pipe Taper (NPT) threaded
• Temperature monitoring: Control and monitoring may be from a single device
• Chamber finish: Chamber must be passivated and electropolished (<30RA)
• Filtration: Air must be vented through 0.2 micron filters before leaving the chamber
• Validation documentation: Internal quality validation acceptable
• Sterilizer control system: Control and monitoring systems meet internal organization requirements for data security

GLP laboratories often use many of the same autoclave cycles as GMP facilities, including gravity, pre-vacuum, liquid, and steam-air mix. However, in addition to these cycles, many GLP labs also rely on an immediate-use (flash) sterilization cycle, which is a type of gravity cycle.

As its name implies, this cycle is performed at a higher temperature than traditional gravity or pre-vacuum cycles for faster sterilization — anywhere from three to five minutes for unwrapped goods, and six to 10 for wrapped goods. Flash cycles are more commonly found in smaller GLP sterilizers and are best suited for labs that need to sterilize high volumes of equipment in relatively little time.

What Is a Non-GMP Sterilizer?

There is a third category of sterilizer broadly referred to as non-GMP sterilizers. These sterilizers fall into one of two categories: basic lab research and GLP. Sterilizers that fall into either of these categories are far less expensive to purchase and maintain than a GMP sterilizer and can be customized to a far greater degree to its intended application.

A majority of the sterilization that takes place in a pharmaceutical or biotechnology facility falls outside the requirements of GMP. Here are some examples of non-GMP sterilizer applications:

• Sterilization of waste materials prior to disposal
• Sterilization of products used for laboratory or R&D purposes and not supporting a production area
• Sterilization of products used for animal and other non-human use testing

For these products, non-GMP sterilizers provide the same service at a fraction of the upfront and operating costs.

Criteria for non-GMP sterilizers are as follows:

• Water source: Can often be fed with tap water, or water with simple filtration or softening
• Sterilizer plumbing: Piping may be constructed from standard brass/bronze NPT fittings for easier replacement and maintenance
• Temperature monitoring: Control and monitoring may be from a single device
• Chamber finish: Chamber may be passivated with standard polish
• Filtration: Sterilized-in-place secondary filter not required
• Validation documentation: Internal quality validation acceptable
• Sterilizer control system: Control and monitoring systems meet internal organization requirements for data security

For a side-by-side comparison of GMP, GLP, and non-GMP sterilizers, refer to the table below:

	GMP Sterilizer	GLP Sterilizer	Non-GMP Sterilizer
Water Source	Must be fed with high-purity water >1 Megaohm sourced from WFI. Steam quality will need to be verified for dryness, superheat and impurities.	Must be fed with high-purity water >1 Megaohm, requiring secondary filtration equipment and storage tanks.	Can often be fed with tap water, or water with simple filtration or softening.
Sterilizer Plumbing	All piping must be constructed from medical grade stainless steel, clamped and orbital welded.	All piping must be constructed from medical grade stainless steel but may be National Pipe Thread Tater (NPT) threaded.	Piping may be constructed from standard brass/bronze NPT fittings for easier replacement and maintenance.
Temperature Monitoring	Temperature monitoring and control must be independent and, therefore, require redundant control systems.	Control and monitoring may be from a single device.	Control and monitoring may be from a single device.
Chamber Finish	Chamber must be polished to mirror finish (<10Ra).	Chamber must be passivated and Electropolished (<30RA).	May be passivated with standard polish.
Filtration	All air must be vented through sterilized-in-place microbial filters with dedicated steam lines.	Air must be vented through 0.2 micron filters before leaving the chamber.	Sterilized-in-place secondary filter not required.
Validation Documentation	Documented QC validation and checkoff required for each stage of installation and sterilization (IQ/OQ/PQ).	Internal QC validation acceptable.	Internal QC validation acceptable.
Sterilizer Control System	Controls compliant with CFR 21 standards for data security.	Control and monitoring systems meet internal organization requirements for data security.	Control and monitoring systems meet internal organization requirements for data security.

 

What Is a Laboratory Sterilizer?

Laboratory sterilizers are most commonly used in universities and for biotechnology, animal and life science, pharmaceutical, food, industrial or biocontainment safety laboratory level 3 applications.

To minimize cost, laboratory sterilizers should be used for all applications that do not require GMP. Red bag waste, products for research and animal testing, and all packaging that does not directly contact a human-use product can be sterilized in non-GMP laboratory sterilizers, even if the primary application of the company’s product is pharmaceutical. Before purchasing an autoclave, perform a thorough analysis of the applications the autoclave will be used for and determine whether GMP sterilization will be required.

For guidance on how to choose the right sterilizer for your application, refer to the flow chart below:

If you’d like more information on laboratory or GLP steam sterilizers, get in touch with the team at Consolidated Sterilizer Systems today.