GMP Compliance Adviser Update No. 1/2021

With this GMP Compliance Adviser UPDATE you have direct access to all prime regulatory changes and to our GMP expert interpretations. Here are the new features at a glance:

GMP in Practice

Current Topics

0.B Cannabis


Chapter 1

Quality Management Systems

1.E Deviation management


Chapter 21

Inspections and drug safety

21.B Dealing with drug risks and GMP violations  

GMP Regulations

Chapter F 

PIC/S Guidelines

F.27 PI 040-1: PIC/S Guidance on Classification of GMP Deficiencies

Chapter H 

WHO Guidelines

H.13 WHO: Good storage and distribution practices for medical products
(Technical Report Series, No. 1025 (2020), Annex 7)

GMP in Practice

Chapter 1 Quality management systems

1.E Deviation management

There is no universal definition for the term "deviation". Each company must therefore determine for itself what is meant by deviations. Usually, this includes at least violations of limits in processes of manufacturing and testing as well as other systems and procedures. The organisational forms and responsibilities within deviation management are also defined on a company-specific basis.
Deviations must be recorded and investigated. During the investigation, the root causes must be analysed in order to define meaningful and effective CAPA actions. The actions are documented in the failure investigation report.
The systematic handling of deviations is subject to a scheme that can be divided into different phases. In principle, care must be taken to ensure that the data and correlations determined are documented in as structured and detailed a manner as possible. This enables the evaluations and the underlying considerations to be traced even after a longer period.
The particular challenge when dealing with deviations is not to be satisfied with hasty explanations (e.g. "human error"), but to investigate the real root causes. This may touch on sensitive areas such as quality awareness and error culture of the individual, but also of the organisation. This can certainly lead to conflicts.
Batch certification and release is one of the special challenges in dealing with deviations. For the evaluation by the qualified person, the deviations must be completed and meet certain requirements. The scope for decision-making when certifying/releasing a batch with a deviation is defined in Annex 16 and takes specific criteria into account.
Deviation management has a direct link to the risk management system and leads to a repeated review of the established risk assessments. Deviation management also interfaces with other elements of quality management such as CAPA, PQR or management review.
The processing of a deviation and the creation of a failure investigation report are explained in detail using examples. (Christian Gausepohl, PhD)

Chapter 21 Inspections and drug safety

21.G Dealing with drug risks and GMP violations

Medicinal products must also be monitored with regard to their safety after their approval. This is necessary because not all side effects and interactions can be recorded during the clinical trial, which are later possible in the context of broad application. The continuous and systematic collection of experience about the effects of drugs is known as pharmacovigilance.
A European safety referral is used to resolve concerns over the safety, efficacy or quality of a medicinal product (or a class of medicines). In a referral, the EMA is requested to conduct a scientific assessment of the products in question on behalf of the European Union (EU).
Within the EU there is a Rapid Alert System (RAS), within which all drug risks are communicated (Rapid Alert Notification, RAN).
Mere quality defects are recorded separately from the pharmacovigilance notifications. An EU standard form has been developed for rapid alert notifications of quality deficiencies.
The findings of a Good Manufacturing Practice (GMP) inspection can have a substantial impact on public health. Reports of serious GMP non-compliance are recorded in the European database EudraGMDP. This means that the information is available to all European authorities and appropriate action can be coordinated.
The Directive 2001/83/EC regulates which actions the authorities can or must take in the case of violations. (Michael Hiob, PhD, Sabine Paris, PhD)

GMP Regulations

Chapter F PIC/S Guidelines

F.27 PI 040-1: PIC/S Guidance on Classification of GMP Deficiencies

Inspection findings resulting in GMP deficiencies can have a considerable impact on any pharmaceutical business, especially if they are considered as significant. This PIC/S guidance clearly categorizes and defines “Critical”, “Major” and “Other” deficiencies based on practical working examples. Along with these examples comes a management tool to support consistent and objective categorization of GMP deficiencies in accordance with risk management principles. Furthermore, it describes the actions that will be taken by inspectorates in response to the findings. This document can be really helpful to prepare for any inspection and will also enhance the understanding of the classification of deficiencies.

Chapter H WHO Guidelines

H.13 WHO: Good storage and distribution practices for medical products (Technical Report Series, No. 1025 (2020), Annex 7)

The guideline Good storage and distribution practices for medical products was published in the WHO Technical Report Series, No. 1025, 2020 as Annex 7. It replaces the two previous documents

  • Chapter H.13: Guide to good storage practices for pharmaceutical products (GSP)
  • Chapter H.14: WHO good distribution practices for pharmaceutical products (GDP).

The areas of transport and storage are thus being combined in one guideline. The scope of application has been expanded from mere pharmaceutical products to "medical products". By WHO definition these are

„products including, but not limited to, finished pharmaceutical products, medical devices including in vitro diagnostic medical devices, and vaccines“.

The guideline is applicable to all entities involved in any aspect of the storage and distribution of medical products, from the premises of the manufacturer of the medical product to an agent, or the person dispensing or providing medical products directly to a patient. This includes manufacturers and wholesalers, as well as brokers, suppliers, distributors, logistics providers, traders, transport companies and forwarding agents.

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