Why GMP? An explanation of Good Manufacturing Practice...!!

GMP refers to the Good Manufacturing Practice Regulations published by the FDA under the Federal Food, Drug, and Cosmetic Act. As a response to concerns about substandard drug manufacturing practices occurring at the time, Congress enacted the 1962 Drug Amendments. These amendments instructed the FDA to require all drugs to be made according to Good Manufacturing Practice (GMP) as defined under FDA 21 CFR Part 210-211.

The first set of Good Manufacturing Practices (GMP) regulations were published in 1963. These regulations are meant to guide companies in the production of safe and effective drugs. The regulations outlined in the GMPs are the minimum requirements necessary to ensure safe and effective products.

In this blog we'll discuss the definition of GMP, various regulatory components, and why it's important for companies in the life sciences space.

Trained inspectors for the FDA examine facilities around the world, including those facilities that produce the active ingredients and final products. The FDA also reviews consumer and industry complaints filed about the drug, using these reports to identify sites that could benefit from inspection.

About GMP

GMP is a set of regulations that ensures the quality of drugs, medical devices, blood, and some types of food. The regulations cover manufacturing, facilities and controls for the manufacturing, processing, packaging or holding of a drug product.

When discussing current good manufacturing practices, many agencies use the acronym cGMP, with the letter ‘c’ standing for ‘current.’ This nomenclature reminds companies to use the most up-to-date technologies and systems in order to comply with current regulations. Many older GMP practices, specifically those designed to prevent errors, mix-ups and contamination, are now outdated and inadequate.

About Part 210 and 211

21 CFR Part 210 and 211 outline the manufacture, processing, packing, or holding of a drug specifically, although supporting companies and services can benefit by compliance with these standards as well.

Part 210.2 applies to drug products intended for human use and lays out definitions for terms used within the document. Part 211 describes important issues.

Its 11 sub-parts discuss all sections of drug manufacturing operations:

1. General Provision

2. Organization and Personnel

3. Building and Facilities

4. Equipment

5. Control of Components and Drug Product Containers and Closures

6. Production and Process Controls

7. Packaging and Labeling Controls

8. Holding and Distribution

9. Laboratory Controls

10. Records and Reports

11. Returned and Salvaged Drug Product

Each section of code outlines a different GMP activity. 211.22 details the responsibilities of a quality control unit, for example, while 211.25 discusses personnel qualifications, 211.28 deals with sanitation, clothing, protective apparel, hygiene and health habits and 211.34 offers guidelines on working with consultants. Part 1271 subparts C and D describes donor-eligibility and applicable current good tissue practice procedures for owners and operators of establishments engaged in the recovery, donor screening, donor testing and other types of testing, processing, storage, labeling, packaging, or distribution of human cells, tissue samples, and cellular and tissue-based products (HCT/Ps).

What GMP Means for Companies in the Life Sciences Space

GMP regulations address a wide range of production activities, including starting materials, sanitation and cleanliness of the premises, equipment verification, and process validation. GMP regulations even extend into human resources and general offices, offering practice guidelines for record keeping, personnel qualifications, complaints, training, and personal hygiene of staff working in regulated areas. GMP requires documented proof of consistent adherence to established procedures at every step in the production process.

While stringent in their requirement for quality, most GMP regulations are open-ended and flexible in that they allow individual companies the latitude to decide on the best way to implement the controls necessary to achieve the highest quality within each organization. Failure to comply with these regulations may result in regulatory action for the drug and for the company responsible for the failure.

Virtually every person in the United States is affected by the quality of pharmaceuticals. Nearly 70 percent of Americans take a prescription drug, according to Mayo Clinic, and almost half take two. The use of non-prescription or over-the-counter (OTC) drugs and supplements is also widespread. cGMPs are important because consumers cannot easily detect an unsafe or ineffective product simply by looking, smelling or touching it. GMP testing, typically performed on small samples from a batch, ensures that the rest of the batch provides the high quality medication or supplementation desired by these consumers.

What is Good Manufacturing Practices (GMP)?

GMP (Good Manufacturing Practice) is part of a quality system covering the manufacture and testing of pharmaceutical dosage forms or drugs and active pharmaceutical ingredients, diagnostics, foods, pharmaceutical products, and medical devices. GMPs are guidance that outlines the aspects of production and testing that can impact the quality of a product.

Quality Assurance / GMP Objectives

Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practice.

• The system of quality assurance appropriate to the manufacture of pharmaceutical products to ensure that:
• Pharmaceutical products are designed and developed in a way that takes account of the requirements of GMP and other associated codes such as those of good laboratory practice (GLP) and good clinical practice (GCP)
• Production and control operations are clearly specified in a written form and GMP requirements are adopted
• Managerial responsibilities are clearly specified in job descriptions
• Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials
• All necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out
• The finished product is correctly processed and checked, according to the defined procedures
• Pharmaceutical products are not sold or supplied before the authorized persons have certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorization and any other regulations relevant to the production, control and release of pharmaceutical products
• Satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products are stored by the manufacturer, distributed, and subsequently handled so that quality is maintained throughout their shelf-life
•  Deviation/complain and recalls are reported, investigated and recorded
• There is a system for approving changes that may have an impact on product quality
• Regular evaluations of the quality of pharmaceutical products should be conducted with the objective of verifying the consistency of the process and ensuring its continuous improvement

What is GMP in Pharmaceutical Products?

Good manufacturing practice is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.

GMP is aimed primarily at diminishing the risks inherent in any pharmaceutical production. Such risks are essentially of two types: cross contamination (in particular of unexpected contaminants) and mix-ups (confusion) caused by, for example, false labels being put on containers.

Good Manufacturing Practice is concerned with both production and quality control.

Under GMP:

>All manufacturing processes are clearly defined, systematically reviewed in the light of experience, and shown to be capable of consistently manufacturing pharmaceutical products of the required quality that comply with their specifications

>Critical steps of manufacturing processes and significant changes to the process are validated;

All necessary facilities for GMP are provided, including

Appropriately qualified and trained personnel Adequate premises and space Suitable equipment and services Appropriate materials, containers and labels Approved procedures and instructions; Suitable storage and transport; Adequate personnel, laboratories and equipment for in-process controls Instructions and procedures are written in clear and unambiguous language, specifically applicable to the facilities provided Operators are trained to carry out procedures correctly Records are made (manually and/or by recording instruments) during manufacture to show that all the steps required by the defined procedures and instructions have in fact been taken and that the quantity and quality of the product are as expected; any significant deviations are fully recorded and investigated Records covering manufacture and distribution, which enable the complete tracing history of the batch, are retained in a comprehensible and accessible form Proper storage and distribution of the products minimizes any risk to their quality are in place and documented A system is available to recall any batch of product from sale or supply

• Complaints about marketed products are examined; the causes of quality defects investigated, and appropriate measures taken in respect of the defective products to prevent recurrence
• no batch of product is released for sale or supply prior to certification by an authorised person that it is in accordance with the requirements of the relevant authorisations

Quality Control is that part of Good Manufacturing Practice which is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory.

The basic requirements of Quality control are that:

• Adequate facilities, trained personnel and approved procedures are available for sampling, inspecting and testing starting materials, packaging materials, intermediate, bulk, and finished products, and where appropriate for monitoring environmental conditions for GMP purposes;
• Samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by personnel and by methods approved by Quality Control;

Test methods are validated;

1. Records are made, manually and/or by recording instruments, which demonstrate that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations are fully recorded and investigated;
2. The finished products contain active ingredients complying with the qualitative and quantitative composition of the marketing authorisation, are of the purity required, and are enclosed within their proper containers and correctly labelled; 
3. Records are made of the results of inspection and that testing of materials, intermediate, bulk, and finished products is formally assessed against specification. Product assessment includes a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures;
4. All batch of product are completely analyzed and approved in accordance with the requirements of the relevant authorization
5. Sufficient reference samples of starting materials and products are retained to permit future examination of the product if necessary and that the product is retained in its final pack unless exceptionally large packs are produced.