GMP Explainer: What and Why?

What is GMP??

GMP stands for Good Manufacturing Practice(s). It comprises a set of rules and standards that govern how pharmaceutical products are made. These guidelines ensure consistent quality, safety, and efficacy throughout the development, manufacturing, and distribution of medicines. Regulatory agencies such as the FDA (Food and Drug Administration, USA), EMA (European Medicines Agency), NMPA (National Medical Products Administration, China), and PMDA (Pharmaceuticals and Medical Devices Agency, Japan) enforce GMP to safeguard patient health. Companies sometimes refer to GxP, where ‘x’ represents specific fields like manufacturing (GMP), laboratory (GLP), or distribution (GDP).

Are GMP and cGMP the same thing??

GMP (Good Manufacturing Practice) and cGMP (Current Good Manufacturing Practice) are often used interchangeably. While both refer to adherence to guidelines and regulations, cGMP specifically emphasizes continuous adjustments. The FDA (and others) expect manufacturers to adapt their quality management systems and approach to product quality to meet the latest regulations, guidelines, and standards. Processes that fulfilled GMP guidelines a decade ago may not necessarily comply with current GMP regulations. Most of the time, when talking about GMP in terms of a manufacturing site , it is used as a shorthand for cGMP.

What are the 5P’s of GMP?

A way to check over the key aspects that are involved in GMP is something called the 5P's. This stands for:

• Personnel (People): Manufacturers must employ qualified and trained personnel with clear roles and responsibilities.
• Premises and Equipment: Adequate facilities and equipment prevent contamination or mix-up of products. Equipment undergoes qualification and calibration.
• Processes: Detailed records track critical manufacturing steps, and production processes are validated.
• Procedures: Documented procedures cover critical processes, deviations are investigated, and change control is well-recorded.
• Products: GMP mandates quality control for raw materials, intermediates, and finished products. Methods are validated, and stability testing is performed.

Why is GMP Important?

GMP ensures consistent, high-quality production, protecting the public from potentially harmful products. Compliance with GMP standards guarantees that pharmaceuticals meet purity, potency, and quality requirements, free from contaminants. It also demonstrates a commitment to producing safe and effective medicines.

Is GMP Difficult?

GMP can indeed be challenging to implement and maintain. It encompasses all aspects of the manufacturing process, from facility design to construction. Achieving GMP compliance requires significant investments in time, resources, and finances. Companies must establish and uphold a comprehensive quality management system, including written procedures, employee training, and meticulous record-keeping. This ongoing process involves continuous monitoring and evaluation to ensure ongoing compliance.

What are the GMP Requirements for Pharma Products?

Whether a pharmaceutical product must adhere to GMP depends on regulations set by relevant agencies like the FDA (Food and Drug Administration) in the United States or the EMA (European Medicines Agency) in Europe. Generally, any active substance (API) intended for human or veterinary use—whether prescription drugs, over-the-counter medications, or dietary supplements—must be manufactured in compliance with GMP guidelines and regulations. GMP may also apply to raw materials, starting materials, and intermediates used in pharmaceutical production, depending on their final use and supporting data. All materials involved in the process must meet quality control (QC) and traceability standards, as their quality directly impacts the safety and efficacy of the final product. However, products intended solely for research use are exempt from GMP regulations. Additionally, different countries may have varying standards, so it’s essential to check local regulations.

Now for some Acronym Explanations...

What are APIs??

APIs (Active Pharmaceutical Ingredients) are crucial components of drugs. They produce the intended therapeutic effect. APIs can be chemically synthesized, obtained through biocatalysis, or extracted from natural sources. These chemically active ingredients are responsible for the desired pharmacological effects of medicines. APIs are typically combined with excipients—inactive ingredients—to create the final dosage form (such as tablets, capsules, liquids, or powders). Ensuring the quality and compliance of APIs is essential, as they play a vital role in pharmaceutical products.

What are NCEs?

NCE stands for New Chemical Entity. This refers to novel chemical compounds or substances that have not previously received approval for use as drugs. These entities emerge from extensive research and development efforts by pharmaceutical companies and research institutions.

• Discovery Methods: NCEs are discovered through various approaches, including screening natural products, synthetic chemistry, phage display and computational methods.
• Evaluation Process: Once an NCE is identified, it undergoes pre-clinical and clinical trials to assess safety, efficacy, and potential side effects. If deemed safe and effective, it can be approved as a new drug and brought to market.
• Innovation Source: NCEs play a crucial role in driving innovation within the pharmaceutical industry, leading to new treatments for unmet medical needs. However, their development is complex, time-consuming, and costly.

What is CMC??

CMC is an acronym for Chemistry, Manufacturing, and Controls, and encompasses critical information required by regulatory agencies to evaluate drug product quality and ensure safety, effectiveness, and consistency.

- Components of CMC Information:

Drug Substance (API): Details about the Active Pharmaceutical Ingredient (API), including its chemical structure, synthesis, and characterization. Drug Product: Information on formulations, manufacturing processes, quality control, and testing. Submission to Regulatory Authorities: CMC data is submitted as part of regulatory documentation to authorities such as the FDA (United States), EMA (Europe), NMPA (China), PMDA (Japan), and other global bodies.

- Regulatory filings include:

• IND (Investigational New Drug): Initial request to the FDA for clinical investigations on new or unapproved drugs.
• NDA (New Drug Application): After IND application and clinical trials, the NDA seeks FDA approval for marketing the drug.
• ANDA (Abbreviated New Drug Application): Submitted for generic drug products, focusing on bioequivalence to an approved product.
• IMPD (Investigational Medicinal Product Dossier): Similar to IND but within the European Union (EU) for clinical trials.
• MAA (Marketing Authorization Applications): Post-IMPD/CTA (Clinical Trial Application), requesting EMA approval for drug marketing.

Importance of CMC

CMC information allows regulatory authorities to evaluate product quality, consistency, and compliance with GMP guidelines.?It ensures that the drug is manufactured in accordance with high standards.The CMC section is critical in drug registration applications, providing insights into quality, safety, efficacy, and the applicant’s manufacturing capabilities.

How to Use This in Practice...

For those that need to engage a GMP supplier or manufacturing partner, there are a number of things to consider. For those moving for the first time to a regulated environment - for example when moving a new innovative treatment from early research towards clinical trials, it can be a daunting experience.

How can I Select a GMP Manufacturer?

• Compliance with Regulatory Requirements: The manufacturer must adhere to relevant GMP regulations and guidelines, such as those set by the FDA (Food and Drug Administration) or the EMA (European Medicines Agency). Verification can be done through certifications and inspections, such as FDA or EMA inspections. Potential customers, may wish to conduct an independent audit.
• Quality Assurance Systems:?The manufacturer should have robust quality assurance systems in place.?These systems ensure that all products meet the highest quality standards.?Guidelines cover design, monitoring, and control of manufacturing processes, as well as quality control testing procedures.
• Experience and Expertise:?The manufacturer should specialize in the specific product or product type.?Expertise in relevant technologies (e.g., synthetic chemistry, fermentation, purification) is crucial. Take time to talk to the technical teams.
• Capacity and Scalability:?Adequate facilities, equipment, and personnel are essential.?Manufacturers should handle project demands and scale production as needed. Flexibility for early-stage toxicology and Phase I studies is valuable due to high attrition rates.
• Communication and Transparency:?Effective communication with clients is vital.?Transparency about processes and quality control procedures is expect.?Detailed technical information and product documentation should be provided.?
• Cost-Effectiveness:?Manufacturers should offer services at a reasonable cost without compromising quality.
• Supply Chain Management:?A secure supply chain ensures continuity of raw materials, intermediates, and final products.
• Technical Support:?Manufacturers should provide technical assistance during the manufacturing process.
• Support and Partnership: Especially for those new to GMP manufacture, having a partnership with a organization that can help navigate some of the regulatory requirements is key. Assisting in preparation of regulatory documentation, advising on best practices and taking a flexible approach in terms of scheduling can all help in this regard.

Biosynth’s Support for GMP Manufacturing

Biosynth are a GMP manufacturer for chemicals, bioconjugates and peptides.

? See GMP Chemicals Services? ?

?See GMP Bioconjugate Services? ?

? See GMP Peptides Services?

Our experienced team collaborates with clients, meeting quality and regulatory needs, assisting in preparing CMC documentation. Biosynth offers regulatory filing assistance, including CMC preparation or review, as well as support for IND/IMPD or NDA/MAA filings.? We understand that the regulatory environment, especially for those moving from a research setting for developing new products and treatments.? Contact us to discuss you needs and to see how Biosynth can work with you to deliver you GMP product from early clinical stage to commercial support.?

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