02.11.2021 | LOGFILE Feature 41/2021

Typical GMP Deficiencies at Manufacturers of Chemical APIs - An Overview

Typical GMP Deficiencies at Manufacturers of Chemical APIs - An Overview

7 min. reading time | by Norbert Waldöfner, PhD


Figure 20.F-24 provides an overview of the GMP deficiencies that, in the author's experience, are frequently encountered during audits of active substance manufacturers.

At a glance: the most common GMP deficiencies at active substance manufacturers


 Insufficient documentation of deviations

 Inadequate root cause analyses

 Lack of risk assessment with regard to further potentially impacted batches

 Insufficient qualification/training of the employees

Quality Risk Management

 No systematic approach

 Superficial risk assessments

 Insufficient follow-up of actions from risk analyses

Product Quality Review

 No in-depth assessment of the available data

 Lack of evaluation of the effectiveness of corrective actions

 Insufficient evaluation of returns

 PQRs are prepared too late.


 Insufficient compliance with hygiene regulations

 Inadequate training of external service providers


 Insufficient monitoring

 Lack of rationale for setting warning and action limits

 Insufficient actions taken when limits are exceeded

Documentation and protocols

 Violations of ALCOA rules and data integrity requirements for electronic systems.

Materials management

 Inadequate pest control measures

 Insufficient sampling conditions

 Insufficient qualification suppliers of raw materials, active substance starting materials and intermediates


 Measures to prevent contamination at different stages of production are inconsistent.

 Lack of definition of the maximum campaign length

 Lack of definition of holding times of uncleaned or cleaned equipment

Packaging and labelling

 Insufficient controls before starting the packaging process

Laboratory controls

 Shortcomings in the examination of OOS results

 Stability samples not stored in containers that mimic market containers.

Cleaning validation

 Insufficient consideration of possible microbiological or endotoxin contamination

 Insufficient care in the identification of worst case products and the selection of sampling points


 Inadequate procedures for handling returns

































Figure 20.F-24 Common GMP deficiencies at active substance manufacturers

Thematically, there is thus a striking overlap here with the deficiencies found during GMP inspections of medicinal product manufacturers (see 21.C Frequent deficiencies in GMP inspections, their recurring pitfalls and how to avoid them). From the author's point of view, the production of active substances generally takes place at a high level; with regard to the fulfillment of the respective GMP requirements, active substance manufacturers are not necessarily in a worse position than medicinal product manufacturers.

Due to the increasing use of electronic systems, it is to be expected that deficiencies in the area of documentation or, for example, the handling of deviations and OOS results will be identified and avoided more quickly in the future. However, this will also result in new sources of errors and requirements, especially with regard to the validation of electronic systems and the maintenance of data integrity. From the author's point of view, the focus of audits at active ingredient manufacturers will certainly continue to shift in the direction of checking these requirements.


Norbert Waldöfner


Norbert Waldöfner, PhD
Auditor at blue inspection body GmbH
E-Mail: norbert.waldoefner@blue-inspection.com

GMP Compliance Adviser

GMP Compliance Adviser

The GMP Compliance Adviser is the most comprehensive GMP online knowledge portal worldwide, combining theory and practice in a successful way.

GMP in Practice: "How-to-do"-interpretations and knowledge of our noted industry specialists and according to international GMP regulations.
GMP Regulations: The most important GMP regulations from Europe, USA, Japan and many more (e.g. PIC/S, ICH, WHO,...).

> More information and order