WHO good manufacturing practices for excipients used in pharmaceutical products – Draft working Document

The World Health Organization wants to update its guideline on manufacturing pharmaceutical excipients to ensure these products meet the requirements for quality and purity that they purport or are represented to possess.
See the new draft working document for comments:


The WHO guideline Good Manufacturing Practices: supplementary guidelines for the manufacture of pharmaceutical excipients, was published in the WHO Technical Report Series No 885, 1999.

As excipients are sometimes used in large quantities in pharmaceutical dosage forms, and may contain impurities, they can affect the quality of a finished pharmaceutical product. The manufacturer of the finished pharmaceutical product is normally dependent on the manufacturer of the excipient to supply excipients meeting the required specification. An appropriately established and implemented quality management system evaluating and controlling risks in the production and quality control of such excipients is therefore required. Some excipient manufacturers may be required to follow good manufacturing practices for excipients used in pharmaceutical products. Reports of pharmaceutical products which contain contaminated excipients, or excipients with impurities leading to the death of patients, have further highlighted the need for a revision of the original guideline. Furthermore, the concept of ongoing improvement, life cycle approach, better quality management systems, risk management and management review should be described in such a guideline, alongside the necessary good storage, good trade and good distribution practices to ensure their reliability throughout the supply chain.

The manufacturer of excipients used in pharmaceutical products should be able to identify risks associated with the production (including stages of manufacturing, route of synthesis) and quality control of its products. This includes, but is not limited to, the premises, equipment, utilities, storage and distribution. The manufacturer of such excipients should assess those risks, and identify appropriate measures to mitigate such risks. The effectiveness of the measures should be evaluated to ensure that they are appropriate.

This document provides information on good manufacturing practices that should be implemented to assist manufacturers to produce and control excipients used in pharmaceutical products that will meet their intended specifications, in a consistent manner. Risk assessment may be useful in determining which excipients should be manufactured in accordance with this guideline.

1. Introduction and scope

1.1. The purpose of this document is to provide guidance for the production, control, storage and distribution of excipients used in pharmaceutical products, focusing on good manufacturing practices (GMP) under an appropriate system for managing quality. It is also intended to help ensure that such excipients meet the requirements for quality and purity that they purport or are represented to possess.

1.2. The document does not cover aspects of protection of the environment, nor safety aspects for the personnel engaged in the manufacture and control of materials and excipients.

1.3. Excipients are often used in large quantities in industrial chemistry, as well as the food and cosmetic industry. Specifications for excipients used in these applications may vary and may not always be appropriate for use in pharmaceutical products. It is the responsibility of the finished product manufacturer and of the applicant to ensure that
the finished product is manufactured using excipients of a suitable grade conforming to its intended use.

1.4. Excipients are often used in significant quantities in the production of pharmaceutical products. They should be of appropriate quality as they could affect the quality of finished pharmaceutical products.

1.5. The manufacturer of the finished pharmaceutical product is highly dependent on the excipient manufacturer to provide materials that are homogeneous in chemical and physical characteristics, and of the desired quality.

1.6. In general, excipients are used as purchased, with no further refining or purification. Consequently, impurities present in the excipient will be carried over to the finished pharmaceutical product.

1.7. To achieve the objective of ensuring that excipients used in pharmaceutical products are of appropriate quality, an appropriate level of GMP should be established, implemented and maintained during their production, packaging, repackaging, labelling, quality control, release, storage, distribution and other related activities. Additional measures
should be taken when manufacturing excipients for which scientific literature, information in the public domain or historical data indicate that they present higher risk because of potential formation of toxic impurities during the manufacturing process, or due to potential contamination during storage and distribution.

1.8. Specific analytical procedures should be used by the excipient manufacturer, where the excipient is intended to be used in a pharmaceutical product, to ensure that it is suitable for its intended use. Pharmacopoeia and regulatory requirements should be considered by the manufacturers as a reference for these analytical tests. Information in the public domain may also be considered. Risk management principles should be implemented in order to identify and mitigate risks.

1.9. A thorough knowledge and understanding of the processes and associated risks are required. This includes all unit operations and processing steps, key steps in the process, critical parameters (time, temperature, pressure, etc.), environment conditions, equipment used, contamination protection and monitoring points.

See the full Draft Working Documents onWHO good manufacturing practices for excipients used in pharmaceutical productshere

(click the picture to download the brochure)

WHO good manufacturing practices for excipients used in pharmaceutical products

Please submit your comments through the online platform, PleaseReview™
If not registered or included in the WHO mailing list, submit your request with full name, email address and organization/affiliation to [email protected]

For any technical questions, you may contact Dr Steve Estevao Cordeiro, Technical Officer, Norms and Standards for Pharmaceuticals, Technical Standards and Specifications ([email protected]), with a copy to Ms Bezawit Kibret ([email protected], [email protected]).

Comments should be submitted through the online platform by 21 May 2023. Please note that only comments received by this deadline will be considered for the preparation of this document.

Source: WHO, Draft Working Documents “WHO good manufacturing practices for excipients used in pharmaceutical products”

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