The Basics of current Good Manufacturing Practices (cGMP)

A set of guidelines for the manufacture, processing, packing, distribution, and storage of medicines. GMP stands for Good Manufacturing Practices.

The FDA ensures the quality of drug products by closely monitoring drug manufacturers’ adherence to Current Good Manufacturing Practices (cGMP) requirements. The cGMP regulations for medications establish minimal standards for the procedures, facilities, and controls used in the production, processing, and packaging of a drug product. The rules ensure that a product is safe to use and that it contains the ingredients and strength that it promises.

“Good practices in production and quality control” outlines steps that should be taken independently by production and quality control staff to implement the general QA standards.

Medicines must comply with GMP guidelines in the following ways:

Are of consistent high quality are suitable for their intended use; and comply with the marketing approval or clinical trial authorization standards.

“Quality management in the pharmaceuticals industry describes the general principles of quality assurance (QA) as well as the major components or subsystems of GMP, which are shared duties of top management and production and quality control management. Hygiene, validation, self-inspection, staff, premises, equipment, supplies, and documentation are some of these.

The cGMP inspection report mostly cover the inspection of all portions including premises, equipment, documentation, materials, validation, sanitation, hygiene, production, quality assurance and utilities.

“Good practices in production and quality control” provides guidelines on actions that production and quality control people should perform individually to implement the general principles of QA. Quality assurance (QA), good manufacturing practices (GMP), quality control (QC), and quality risk management (QRM) are all interrelated components of quality management that should be the responsibility of all personnel.

QA is a wide-ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. QA, therefore, incorporates GMP and other factors, including those outside the scope of this guide such as product design and development. The system of QA appropriate to the manufacture of pharmaceutical products should ensure that: (a) 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); as those of good laboratory practice (GLP)73 7 and good clinical practice (GCP); (b) production and control operations are clearly specified in a written form and GMP requirements are adopted; (c) managerial responsibilities are clearly specified in job descriptions; (d) arrangements are made for the manufacture, supply and use of the correct starting and packaging materials; (e) all necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out; (f) the finished product is correctly processed and checked, according to the defined procedures; (g) pharmaceutical products are not sold or supplied before the authorized persons (see also sections 9.11 & 9.12) 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; (h) 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; (i) here is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness and applicability of the QA system; (j) deviations are reported, investigated and recorded; (k) there is a system for approving changes that may have an impact on product quality; (l) regular evaluations of the product quality; (l) 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; and (m) there is a system for QRM.

To achieve the quality objective, there must be a comprehensively designed and correctly implemented system of Quality Assurance. This should incorporate both Quality Assurance and Quality Control. The Quality Systems must be fully documented and its effectiveness monitored.

All parts of the Pharmaceutical Quality Assurance program should be adequately staffed with competent personnel, and should have suitable and sufficient premises, equipment and facilities. 1.4 QRM is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively. 1.5 QRM should ensure that: — the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient; and — the level of effort, formality and documentation of the QRM process is commensurate with the level of risk.

GMP is that part of QA 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 are 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. Under GMP: (a) 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; (b) qualification and validation are performed; (c) all necessary resources are provided, including: (i) appropriately qualified and trained personnel;

(ii) adequate premises and space; (iii) suitable equipment and services; (iv) appropriate materials, containers and labels; (v) approved procedures and instructions; (vi) suitable storage and transport; (vii) adequate personnel, laboratories and equipment for in-process controls; (d) instructions and procedures are written in clear and unambiguous language, specifically applicable to the facilities provided; (e) operators are trained to carry out procedures correctly; (f) 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; (g) records covering manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form; (h) the proper storage and distribution of the products minimizes any risk to their quality; (i) a system is available to recall any batch of product from sale or supply; (j) complaints about marketed products are examined, the causes of quality defects investigated, and appropriate measures taken in respect.

Sanitation and hygiene 3.1 a high level of sanitation and hygiene should be practiced in every aspect of the manufacture of medicines products. The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus, production materials and containers, products for cleaning and disinfection, and anything that could become a source of contamination to the product. Potential sources of contamination should be eliminated through an integrated comprehensive programmed of sanitation and hygiene. (For Personal hygiene see section 11, and for sanitation see section 12, “Premises”.) 4. Qualification and validation 4.1 In accordance with GMP, each pharmaceutical company should identify what qualification and validation work is required to prove that the critical aspects of their particular operation are controlled. 4.2 The key elements of a qualification and validation programmed of a company should be clearly defined and documented in a validation master plan.

Qualification and validation should establish and provide documentary evidence that: (a) the premises, supporting utilities, equipment and processes have been designed in accordance with the requirements for GMP (design qualification or DQ); (b) the premises, supporting utilities and equipment have been built and installed in compliance with their design specifications (installation qualification or IQ); (c) the premises, supporting utilities and equipment operate in accordance with their design specifications (operational qualification or OQ); (d) a specific process will consistently produce a product meeting its predetermined specifications and quality attributes (process validation or PV, also called performance qualification or PQ).

Guidance on good data and record management practices

“If it isn’t documented, it didn’t happen,” as the saying goes in the pharmaceutical industry.

As a result, pharmaceutical and medical device industries document every thing to provide written proof that something occurred.

As a result, effective documentation practices, often known as GDPs, are crucial. The only official, documented record of:

 • processing a batch

• producing a device

• Final decision to release (or reject) a batch or product

• Evidence for a corrective or preventive action (CAPA)

• An investigation of manufacturing deviations, complaints, or alleged product defects

• meeting product and quality specifications generated from test is also, in addition to regulatory requirements.

The “history/storyline” of manufactured products and devices is told through records, reports, and procedures.

In addition to meeting regulatory requirements, it is critical to keep accurate records for commercial purposes. You can take a critical look at numerous processes associated to product manufacture with the goal of improving quality, product, or cost savings by keeping clear, accurate, and timely records.

Everyone who documents activities connected to cGMP or current Good Manufacturing Practices is subject to GDPs.

Good Documentation Practices are required to comply with the Food and Drug Administration’s GLP (Good Laboratory Practices) requirements (21 CFR Part 58), as well as GMP (Good Manufacturing Practices) regulations for medicines and medical devices (21 CFR Parts 211 and 820).

What types of documents require following Good Documentation Practices?

Some examples include:

• Analytical Methods

 • Batch Records

• Bills of Materials (BOMs)

• Certificate of Analyses (CoA)

 • Certificate of Compliance (CoC)

 • Laboratory Notebooks

• Policies

• Protocols • Quality records

• Standard Operating Procedures

• Test Methods

 • Training Documentation

• Validation Documents (IQs, OQs and PQs)

 • Work Instructions

• Product and Sample Labels Categories of Documents

1. Primary records such as those obtained from the master formula, manufacturing and packaging instructions.

 2. Supporting procedures such as instructions on how to perform a manufacturing step or test methodology.

3. Subsidiary records which support the process as it is being carried out, such as environmental monitoring or preventive maintenance/calibration on process or lab equipment. 4. Quality control records include all lab testing results for the process or products and al investigative reports and records.

Organizations that develop, manufacture, package, test, distribute, and monitor pharmaceutical products have mainly depended on the knowledge of regulatory systems around the world. 

The information submitted in dossiers (CTD) and used in day-to-day decision making is thorough, complete, and trustworthy data.  As a result, the information on which these decisions are based must be comprehensive, widely attributed, readable, current, original, and correct, commonly referred to as “ALCOA”. 

  • A: Attributable
  • L: Legible
  • C: Contemporaneous
  • O: Original
  • A: Accurate

ALCOA-plus. A commonly used acronym for “attributable, legible, contemporaneous, original and accurate”, which puts additional emphasis on the attributes of being complete, consistent, enduring and available – implicit basic ALCOA principles.

Increased regulatory knowledge and concern about gaps between industry choices and acceptable and modern control procedures are only a few of the reasons why health authorities are becoming increasingly concerned about data reliability.

Intense attention has been put forward on good data and record management practices (GDRP) during inspections of good manufacturing practice (GMP), good clinical practice (GCP) and good laboratory practices (GLP) because of increasing concern of health authorities regarding data reliability to meet the standards of desired pharmaceutical product and clinical practices.

Data management strategies must include Quality Risk Management (QRM) strategy that ensures patient safety, product quality, and data validity by ensuring that management aligns expectations with real process capabilities. Management should assume responsibility for good data management by first establishing realistic and achievable expectations for the realistic and existing capabilities of processes, methods, environments, individuals, and technologies, among other things.

Management’s monitoring of processes and allocation of necessary resources to ensure and improve infrastructure as needed (for example, to continuously improve processes and methods, to ensure adequate design and maintenance of buildings, facilities, equipment, and systems; to ensure adequate reliable power and water supplies; to provide necessary training for personnel; and to allocate necessary resources to the oversight of contract sites and suppliers to ensure and improve infrastructure as needed).

A planned set of controls that ensures protocol compliance, process performance, product quality, and data dependability, if appropriate, based on current protocol, test article and process understanding. Study subjects, test systems, product materials and components, technologies and equipment, and operating circumstances should all be included in the controls.

The activities done to improve an organization’s operations and reduce causes of non-conformities or other undesirable events are referred to as corrective action and preventative action (CAPA). CAPA is a notion that may be found in the GXPs (good laboratory practices, good clinical practices, and good manufacturing practices) as well as a number of business standards from the International Organization for Standardization.

The method focuses on a systematic analysis of the root causes of identified problems or risks in order to prevent recurrence (for remedial action) or the occurrence of such problems or risks (for preventive action).

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