cGMP regulations in pharmaceutical industry

Introduction

The pharmaceutical industry is strictly regulated, mainly by the legal authorities of their respective countries. Pharma product manufacturers must adhere to relevant market regulations in which they plan to manufacture or market their products. Every country or region has regulations, including the GMP –Good Manufacturing Practices. These practices are the guidelines for pharma manufacturers that manufacture or market their products in the United States of America. They are put into law by the Food and Drug Administration – FDA.

What is the definition of GMP?

There is no specific definition of a GMP. However, the FDA website states that GMP regulations for a pharma drug contain minimum requirements for methods, facilities and control used in manufacturing, processing and packing. The regulation's main aim is to ensure the product is safe for human use. Additionally, it contains the desired ingredients and strength as per the claim.

GMP has the status of law and focuses on quality in the final finished drug. Quality ensures the final product is safe from errors, contamination and mix-up.  

Some areas of the pharma industry that address GMP regulations include documentation, personal expertise and qualification, cleanliness, equipment and process validation. It is the responsibility of individual pharma manufacturers to interpret this regulation according to its requirements and implement it in a way that benefits its customer and simultaneously fulfils regulatory requirements.

If any pharma manufacturer fails to comply with the cGMP regulations, it can result in warnings, fines and even shutting down manufacturing operations.

Importance of cGMP manufacturing

Let’s look at some importance of GMP in pharma manufacturing and see how it benefits the pharma manufacturer

Compliance

Implementation of GMP guidelines ensures FDA compliance for a pharma manufacturer. It allows them to market and sell their products in the United States market. It prevents the pharma manufacturer from receiving warnings, fines or shutting down manufacturing operations from the FDA.

Products Safety

Complying with all the GMP requirements induces quality in the entire product life cycle  - from start to finish, ultimately producing quality in the final product. Because quality cannot only be included in the

Customer Trust

Adherence to GMP regulations creates trust in the customer's mind, increasing the pharma manufacturer's credibility and market share. It makes the customer confident they get the right value for the money spent.

Buildings and Equipment are in right condition

GMP regulations cover the entire aspects of pharma manufacturing, including the building and equipment. These directly impact product quality and safety. Following all GMP regulations ensures that equipment and building are maintained according to the product’s production requirements, quality is maintained, and drugs deliver the required therapeutic effects.

Process Credibility

GMP regulations also focus on processes involved in product manufacturing. It ensures process credibility by implementing appropriate documentation, validation activities and quality testing at various stages. These help in creating and maintaining process credibility throughout the entire production cycle.

FDA regulations for cGMP

Let’s discuss some regulations of GMP in pharmaceutical industry

21 CFR Part 314 – For FDA approval to market a new drug.

21 CFR part 314 is the FDA regulations regarding “Application for FDA approval to market a new drug”. These regulations cover requirements set forth by the FDA under section 505 and do not cover regulations covered under the “Public Health Service Act” section. These regulations facilitate the approval of safe and effective drugs while also disapproving unsafe and ineffective drugs.

Some important points under 21 CFR part 314 include the following.

• NDA is required to be signed and submitted on the prescribed form. 

• Application form containing information such as Name and address of the applicant, NDA date and number, drug detail, indicating the OTC status.

• A summary indicating the proposed text of labelling, clinical benefits, pharmacologic class and scientific rationale.

• Marketing history outside of the United States, if applicable

• Benefits and risk consideration of Drug

• A dedicated section using graphs and tables indicates the pharmacological actions and toxicological effects of drugs, effects on the reproduction and developing fetus, and whether studies are conducted under Good Laboratory Practices – GLP in the case of non-clinical laboratory study.

• Summary of pharmacokinetics and metabolism study of the active ingredients and their bioavailability.

• Microbiological data such as biochemical basis, antimicrobial spectra, and any known mechanism of resistance to the Drug

• Clinical data such as clinical pharmacology of Drugs, protocol and description of statistical analysis.

• Study and results related to safety and effectiveness of Drugs.

• Studies and results of abuse related to Drugs, if present

• The investigation related to Drug’s safe and effective usage in the pediatric population, including clinical pharmacological studies, controlled and uncontrolled clinical studies

• Sample of drug product including Drug for marketing, drug substance used in manufacturing, reference standards & blanks and finished market sample.

• Three copies of analytical procedures must be provided.

21 CFR Part 210 – Current Good Manufacturing Practice in Manufacturing Processing, Packing, or Holding of Drugs.

The 21CFR 210, subchapter C deals with regulations related to drug of generalized category, and its part 210 is called CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL.

The CFR210 is divided into three sections – 210.1, 210.2 and 210.3. Some important points of this regulation include the following

• The regulations set forth are the minimum requirements for a pharma manufacturer and include processes such as manufacturing, processing, packing and holding of a drug form so that the drug is safe, contains the desired strength, and meets the quality and purity characteristics. 

• If a pharma manufacturer fails to comply with the regulations related to processing, manufacturing, packing and holding, the drug shall be rendered adulterated under section 501(a)(2)(B). The drug and the responsible person shall be subjected to regulatory action

• Pharma manufacturers engaged in recovery, donor screening, testing (including donor testing), processing, storage, labelling, packaging, or distribution of human cells, tissues, and cellular and tissue-based products (HCT/Ps), as defined in § 1271.3(d), and under section 505 of the act or section 351 of the Public Health Service Act), are subject to the donor-eligibility and applicable current good tissue practice procedures outlined in part 1271 subparts C and D of this chapter, in addition to the regulations in this part and parts 211, 225, and 226 of this chapter. If a manufacturer fails to comply with these regulations in manufacturing, packing, processing and holding, the drug and the responsible person shall be subject to regulatory action.

21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals.

The 21CFR 211, subchapter C, deals with regulations related to drugs of generalized category, and its part 211 is called Current Good Manufacturing Practice for Finished Pharmaceuticals. These regulations contain minimum requirements for manufacturing drug products for humans or animals. According to these regulations, drug products are 

• Defined as per parts 600 through 680

• Biological products for human use

• Part 1271 of this chapter

• Drugs that are also human cells, tissues, cellular and tissue-based products

• Application of a drug submitted under section 505

• Application of a biological drug submitted under section 351 of the public Health Service Act

21CFR part 211 regulation is divided into 11 parts, from subpart A to subpart K. Some brief description is mentioned below

• Subpart A : General provision and definition of drug that is covered under this regulation

• Subpart B Organization and Personnel :

• Requirement and responsibilities of a quality control unit

• Personnel qualification i.e. minimum education, training and experience requirement of personnel involved in manufacturing, processing, packing and holding of pharma product.

• Subpart C Building and Facilities: This subpart provides building and facilities requirements, and is divided into following sections

• Design and construction features

• Lightening requirements

• Heating Ventilation and Air Conditioning – HVAC

• Plumbing

• Sewage

• Washing and Toilet facilities

• Sanitation

• Maintenance

• Subpart D Equipment: This subpart provides regulations for the equipment used in manufacturing, processing, packing and holding of a pharma drug. Some areas of equipment that it covers includes the following

• Design and size

• Equipment construction

• Cleaning and maintenance

• Automatic, electronic and mechanical equipment

• Filters

• Subpart E Control of components and drug product containers and closures: This section provides guidelines for receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures. Some areas that it covers includes the following

• General requirements

• Receipt and storage of untested components, drug product containers, and closures.

• Testing and approval or rejection of components, drug product containers, and closures.

• Use of approved components, drug product containers, and closures

• Retesting of approved components, drug product containers, and closures.

• Rejected components, drug product containers, and closures.

• Drug product containers and closures

• Subpart F Production and Process Control: This part provides regulations related to production and process control for drug manufacturing, processing, packing and holding. This section is divided into the following

• Written procedures, deviations

• Charge – in of components

• Yield calculation

• Equipment identification

• Sampling and testing of In-process materials and drug products

• Time limitation on production

• Control of microbiological contamination

• Reprocessing

• Subpart G Packaging and Labeling Control: This part provide guidance for packaging and labeling of a pharma product, and includes the following section

• Materials examination and usage criteria

• Labels issuance

• Packaging and labeling operations

• Tamper evident packaging requirements for OTC drugs

• Drug product inspection

• Expiration date

• Subpart H Holding and Distribution: These regulations provide guidelines for drug products that are hold, and are released for distribution. This section include the following section

• Warehousing operations

• Distribution procedures

• Subpart I Laboratory Controls: This subpart provides guidelines for laboratory controls for a pharma drug, and includes the following

• General requirements

• Testing and release for distribution

• Stability testing

• Special testing

• Reserve samples

• Laboratory animals

• Penicillin contamination

• Subpart J Records and Reports : This section provides guidelines on how to take records and maintain according to highest standards. Section that are includes are mentioned below

• General requirements

• Equipment cleaning and use log

• Component, drug product container, closure, and labeling records

• Master production and control record

• Batch production and control record

• Production record review

• Laboratory records

• Distribution record

• Complaint files

• Subpart Returned and Salvaged Drug Products: This section provides guideliens for the pharma drug that have been returned back for any reason. Some section, included in this part are mentioned below

• Returned drug products

• Drug product salvaging

21 CFR Part 212 – Current Good Manufacturing Practice for Positron Emission Tomography Drugs.

21CFRpart 212 are the GMP regulations for positron emission tomography drugs. These regulations are further divided into 12 parts – from subpart A through L,, and includes the following

• Subpart A General Provisions

• Subpart B Personnel and resources

• Subpart C Quality Assurance

• Subpart D facilities and equipment

• Subpart E Control of components, Containers, and Closures

• Subpart F Production and Process Control

• Subpart G Laboratory Controls

• Subpart H Finished drug product controls and acceptance

• Subpart I Packaging and Labeling

• Subpart J Distribution

• Subpart K Complaint handling

• Subpart L Records

21 CFR Part 600 – Biological Products: General.

The 21CFR part 600 are GMP regulations for general biological products. These guidelines further includes four subparts – from subpart A through D, and includes the following subparts

• Subpart A – General requirement

• Subpart B – Establishment standards

• Subpart C – Establishment Inspection

• Subpart D – Recording of Adverse experiences

About the Author

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.