Current Good Manufacturing Practices for Pharmaceutical
Products (GMP) As per WHO
Good manufacturing practice is that part of quality assurance which ensures
that product is 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 essential 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 are taken in respect of the defective products to prevent a recurrence.
GOOD MANUFACTURING PRACTICE GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS (Q7) ICH
This document (Guide) is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the requirements for quality and purity that they purport or are represented to possess.
In this Guide “manufacturing” is defined to include all operations of receipt of materials, production, packaging, repackaging, labeling, relabelling, quality control, release, storage, and distribution of APIs and the related controls. In this Guide, the term “should” indicates recommendations that are expected to apply unless shown to be inapplicable or replaced by an alternative demonstrated to provide at least an equivalent level of quality assurance. For the purposes of this Guide, the terms “current good manufacturing practices” and “good manufacturing practices” are equivalent. The Guide as a whole does not cover safety aspects for the personnel engaged in the manufacture, nor aspects of protection of the environment. These controls are inherent responsibilities of the manufacturer and are governed by national laws.
This Guide is not intended to define registration/filing requirements or modify pharmacopoeial requirements. This Guide does not affect the ability of the responsible regulatory agency to establish specific registration/filing requirements regarding APIs within the context of marketing/manufacturing authorizations or drug applications. All commitments in registration/filing documents must be met.
This Guide applies to the manufacture of APIs for use in human drug (medicinal) products. It applies to the manufacture of sterile APIs only up to the point immediately prior to the APIs being rendered sterile. The sterilization and aseptic processing of sterile APIs are not covered by this guidance but should be performed in accordance with GMP guidelines for drug (medicinal) products as defined by local authorities.
This Guide covers APIs that are manufactured by chemical synthesis, extraction, cell culture/fermentation, by recovery from natural sources, or by any combination of these processes. Specific guidance for APIs manufactured by cell culture/fermentation is described in Section 18(ICH Q7).
This Guide excludes all vaccines, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fractionation), and gene therapy APIs. However, it does include APIs that are produced using blood or plasma as raw materials. Note that cell substrates (mammalian, plant, insect or microbial cells, tissue or animal sources including transgenic animals) and early process steps may be subject to GMP but are not covered by this Guide. In addition, the Guide does not apply to medical gases, bulk-packaged drug (medicinal) products, and manufacturing/control aspects specific to radiopharmaceuticals.
Section 19 (ICH Q7) contains guidance that only applies to the manufacture of APIs used in the production of drug (medicinal) products specifically for clinical trials (investigational medicinal products).
An “API Starting Material” is a raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API Starting Material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API Starting Materials normally have defined chemical properties and structure.
The company should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which “API Starting Materials” are entered into the process. For other processes (e.g. fermentation, extraction, purification, etc), this rationale should be established on a case-by-case basis. Table 1 gives guidance on the point at which the API Starting Material is normally introduced into the process.
From this point on, appropriate GMP as defined in this Guide should be applied to these intermediate and/or API manufacturing steps. This would include the validation of critical process steps determined to impact the quality of the API. However, it should be noted that the fact that a company chooses to validate a process step does not necessarily define that step as critical.
The guidance in this document would normally be applied to the steps shown in gray in Table 1(ICH Q7). It does not imply that all steps shown should be completed. The stringency of GMP in API manufacturing should increase as the process proceeds from early API steps to final steps, purification, and packaging. Physical processing of APIs, such as granulation, coating or physical manipulation of particle size (e.g. milling, micronizing), should be conducted at least to the standards of this Guide.
This GMP Guide does not apply to steps prior to the introduction of the defined “API Starting Material”.
Good Manufacturing Practice for Medicinal Products EU GMP
1.8 Good Manufacturing Practice is that part of Quality Management which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the Marketing Authorisation, Clinical Trial Authorisation or product specification. Good Manufacturing Practice is concerned with both production and quality control. The basic requirements of GMP are that;
(i) All manufacturing processes are clearly defined, systematically reviewed in
the light of experience and shown to be capable of consistently manufacturing
medicinal products of the required quality and complying with their
(ii) Critical steps of manufacturing processes and significant changes to the process are validated;
(iii) All necessary facilities for GMP are provided including:
• Appropriately qualified and trained personnel;
• Adequate premises and space;
• Suitable equipment and services;
• Correct materials, containers, and labels;
• Approved procedures and instructions, in accordance with the Pharmaceutical Quality System;
• Suitable storage and transport;
(iv) Instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided;
(v) Procedures are carried out correctly and operators are trained to do so;
(vi) Records are made, manually and/or by recording instruments, during manufacturer which demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the product were as expected.
(vii) Any significant deviations are fully recorded, investigated with the
the objective of determining the root cause and appropriate corrective and preventive action implemented;
(viii) Records of manufacture including distribution which enable them a complete history of a batch to be traced are retained in a comprehensible and accessible form;
(ix) The distribution of the products minimizes any risk to their quality and takes account of Good Distribution Practice;
(x) A system is available to recall any batch of product, from sale or supply;
(xi) Complaints about products are examined, the causes of quality defects investigated and appropriate measures are taken in respect of the defective products and to prevent reoccurrence.
Good manufacturing practice (GMP) AS PER MHRA
Good manufacturing practice (GMP) is the minimum standard that a medicines manufacturer must meet in their production processes. Products must:
- be of consistently high quality
- be appropriate to their intended use
- meet the requirements of the marketing authorization (MA) or product specification
Good distribution practice (GDP) requires that medicines are obtained from the licensed supply chain and are consistently stored, transported and handled under suitable conditions, as required by the MA or product specification.
Organizations that may have to comply with good manufacturing practice (GMP) and/or good distribution practice (GDP) include:
- manufacturer license holders
- wholesale dealer license holders
- blood establishment authorization holders
- non-UK sites employed by UK MA holders
MHRA carries out inspections to check if manufacturing and distribution sites comply with GMP or GDP. You will be inspected when you apply for a manufacturer or wholesaler dealer license and then periodically based on risk assessments. Overseas manufacturing sites are also inspected.
GLP and GMP
The term Good Laboratory Practice (GLP) is a generic term that causes confusion when used to describe the quality control testing of medicinal products. Compliance with the OECD Principles of GLP is a regulatory requirement when conducting non-clinical safety studies of new chemical or biological substances. There is no legal requirement for the quality control testing of the medicinal product to be conducted in accordance with the OECD Principles of GLP and there is no requirement for laboratories involved in quality control testing of medicinal products to be members of the UK GLP Compliance Monitoring Programme.
EU cGMP – vol4-chap1_2013-01_en
Q7ICH – GOOD MANUFACTURING PRACTICE GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS