Cell-Based Assay Validation Under GLP or GMP — What Pharma Teams Need to Know

GMP and GLP are industry-specific guidelines for compliance in the stages of design, testing, manufacturing and distributing healthcare products. Proper protocols and the validation of processes is critical in producing replicable results that adhere to industry standards.

Generally speaking, GLPs are research and study-focused, while GMPs are production and process-focused. However, they have a few other significant differences better understood by defining each.

Documentation

• GLP: Focuses on study protocols, raw data, and final reports to ensure study reproducibility. This includes detailed records of study design, execution, and results analysis. It requires a study director, the data needs to be peer reviewed, and the method run under a SOP/WIN.  The level of validation will very much dependent on the intended purpose. The GMP regulations are not applied to areas where safety assessments are not a concern for discovery, in vitro studies, screening, and basic research studies.

• GMP: Emphasizes comprehensive documentation of manufacturing processes, batch records, and product testing to ensure traceability and compliance. This includes everything from the raw materials used to the final product packaging. The data needs to be peer reviewed, and the method run under a SOP/WIN.  Unless the method is used to measure safety, it will not need to be validated at this point for Phase I and II.  It will need some demonstration of assay performance.

GLP provides tools and resources to ensure the high standard management of nonclinical laboratory studies. It assures the quality, reliability, and data integrity and validity generated during testing of studies, the reporting of verifiable conclusions, and data traceability. GLP protects the public from any fraudulent health practices.

What is GLP?

Good Laboratory Practice (GLP) is a set of principles and regulations intended to ensure the quality, integrity, and reliability of non-clinical laboratory studies. These studies are essential in supporting research and development, particularly in the safety and efficacy testing of chemicals, pharmaceuticals, and other products before they enter clinical trials or the market.

Key Aspects of GLP:

1. Study Protocols: GLP emphasizes the need for detailed and standardized study protocols. These protocols ensure consistency and reproducibility across different studies and laboratories.
2. Record Keeping: Comprehensive documentation is required for all aspects of the study, from initial planning through raw data collection to final reports. This documentation is critical for verifying study outcomes and ensuring traceability.
3. Quality Assurance: Independent quality assurance units must review study processes and data integrity to ensure compliance with GLP standards. This oversight helps to maintain the integrity of the data collected. And  these QA units are separate from the operational teams to provide an unbiased review of the study processes and results.
4. Personnel Training: Adequate training and qualifications for all personnel involved in the study are mandated under GLP. This ensures that the individuals conducting and overseeing the studies are competent and knowledgeable about the regulatory requirements and scientific methodologies.

GLP primarily applies to preclinical studies, such as toxicity testing, pharmacokinetics, and other non-clinical investigations. Its ultimate goal is to protect public health by ensuring that the data generated is reliable and can be confidently used for regulatory submissions.

GLP compliance monitors conditions, processes, documentation, and archiving of studies performed in laboratory settings. Such endeavors require highly accurate and trackable data as well as high-quality results in order to validate and market the final product. The integrity of the data is critical for developing replicable results, as well as the product’s progress to market.

GLPs were first established in the 1970s by the FDA, to assess nonclinical pharmaceutical lab study safety, including in vitro and ex vivo test systems supporting research and marketing of biocompatibility, toxicology, pharmacology, and other medical products. GLP regulates nonclinical laboratory studies researching or marketing drugs for humans and animals, human cells/tissues, food color additives, perfumes, medical devices, biologics, and pesticides.

GLP is designed to protect the integrity of the study’s scientific data, providing the verifiable record of open-ended research studies necessary for advancement of the product. During “test systems” studies, GLP is also necessary in regards to handling live organisms or microorganisms, as well as plants. In addition, safety and efficacy testing should be performed under GLP.

What is GMP?

Good Manufacturing Practice (GMP) encompasses regulations designed to ensure that products are consistently produced and controlled according to quality standards. GMP is particularly critical during the production phase, especially for pharmaceuticals, medical devices, food, and cosmetics.

Key Aspects of GMP:

1. Production Processes: GMP requires well-defined and controlled manufacturing processes. These processes are essential to ensuring product quality and uniformity from batch to batch.
2. Facility and Equipment: Clean and controlled environments, along with properly maintained equipment, are essential to prevent contamination and ensure product consistency. Facilities must be designed to minimize risks and allow for thorough cleaning and maintenance.
3. Quality Control: Continuous monitoring and testing of products to meet specified quality criteria is a cornerstone of GMP. This includes in-process controls, final product testing, and stability testing to ensure the product meets all required specifications.
4. Documentation and Records: Detailed documentation for every aspect of the manufacturing process, including batch records, is necessary for traceability and accountability. This ensures that any issues can be traced back to their source, and corrective actions can be implemented effectively.

In the pharmaceutical industry, GMP is particularly critical due to the potential impact of product quality on patient safety. GMP regulations in pharma ensure that drugs are produced to the highest quality standards, minimizing risks such as contamination, incorrect labeling, and variations in potency. The consequences of failing to adhere to GMP can be severe, including product recalls, legal action, and harm to patients.

GMP compliance refers to quality assurance throughout the manufacturing processes, and includes in-process controls, final product testing, and stringent quality control measures as defined by the local regulatory body to ensure the safety of healthcare products sold in their jurisdiction. “cGMP,” which is essentially just “current” GMP, outlines the specific conditions under which manufacturing can and should occur. The “current” means up to date methods used. Such guidelines cover, among others, the conditions of lighting, plumbing, hygiene, storage, equipment maintenance, and separation of substances to avoid contamination. Quality assurance in GMP is integrated into every stage of production to catch and correct issues in real-time.

GMP compliances are required during the batch/lot release (or lot conformance), manufacturing and testing, and medical product marketing phases. Furthermore, the testing phase of components used in clinical trials (active pharmaceutical products (API, DS), Drug Product (DP) critical excipients), testing of stability, process validation, and other supporting activities must also follow GMP regulations. Some investigational drug products and biologics in clinical trials may not require full GMP compliance. They may instead specify a number of “relevant” regulations to which to adhere.

GMP regulations contain some best practices for industries to help ensure the safety, quality, and efficacy of food, drugs, medical devices, and cosmetics. They enable companies and labs to minimize or eliminate instances of contamination, mixups, and errors. GMP addresses issues related to record-keeping, personnel qualifications, sanitation, cleanliness, equipment verification, process validation, and complaint handling. It protects customers from buying medicines and foods that may cause adverse effects on their health or harm them in any way.

GMP was first established in 1938 by the FDA to monitor manufacturing quality of food, drugs, medical devices, and cosmetics. GMP is designed to ensure that each product batch is manufactured properly in accordance with pre-approved quality requirements.