GMP Compliance Adviser Update No. 4/2019

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

Chapter 14 14.C Qualification of laboratory equipment
14.K Pharmacopoeias
Please note: The order of the chapters 14.C-14.O has been changed for editorial reasons.

GMP Regulations

Chapter C

C.16 Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container

Chapter D

D.1.1–D.1.9 21 CFRs 4, 11, 210, 211, 600, 601, 606, 680 and 820
D.19 Guidance for Industry: Considerations in Demonstrating Interchangeability with a ReferenceProduct
D.21 Guidance for Industry: Questions and Answers

Chapter G

G.2 Canadian Regulations
G.2.1 Good manufacturing practices guide fordrug products (GUI-0001)
G.2.2 Annexes to GUI-0001

GMP in Practice

Chapter 14 Laboratory controls

14.C Qualification of laboratory equipment

This new chapter enables readers to qualify laboratory equipment in compliance with the regulatory requirements either themselves or through external service providers. Together with a presentation of various qualification concepts and potential errors and pitfalls from practical experience, it provides approaches to solutions for implementing the qualification of laboratory equipment economically and in compliance with GMP requirements.

The responsibilities for both equipment qualification and software validation are described and important terms used in the area of equipment qualification are explained. Various concepts for the qualification of standard devices and special systems are presented. The advantages and disadvantages of internal and external implementation are also weighed against each other.

After initial qualification of the laboratory equipment, the qualified status must be maintained throughout the life cycle of the equipment. An important issue here is the interaction of requalification, repair and maintenance under the umbrella of change control. In this context, the system suitability test, calibration and the handling of OOC results are also explained.

All important documents used in the area of device qualification and their contents are described, including typical qualification documentation as well as equipment-specific documents such as release information, the factsheet or the logbook.

This set of equipment qualification tools is supplemented by the scope of qualification testing for a number of typical pieces of laboratory equipment as well as example documents for the various qualification phases.

The topic of laboratory software is also broached and various approaches to solutions for the validation of computer-aided laboratory systems are presented. (Markus Limberger, PhD, Christian Perlick, PhD)

14.K Pharmacopoeias

Pharmacopoeias provide publicly available standards, specifications and test methods for medicinal products and substances used therein. The most important pharmacopoeias, discussed here, are the European, British, United States, Japanese and International Pharmacopoeias. Their relationship to the regulatory authorities varies. A pharmacopoeia organisation can be part of the regulatory authority (Japan), an independent organisation (USA) or an intermediate form. As a rule, regulatory authorities expect conformity with the provisions of the applicable pharmacopoeia.

This chapter provides an overview of the structure and use of pharmacopoeias. It also presents some special features of the most important compendia.

Pharmacopoeia monographs are dynamic, in that they are regularly revised and updated due to constantly evolving quality requirements. The pharmaceutical industry is given the opportunity to contribute to the elaboration of monographs and to their further development after publication and during application through comments and annotation. Initiatives are in progress through the International Conference on Harmonisation (ICH) to harmonise general test methods and excipient monographs. (Markus Veit, PhD)

GMP Regulations

Chapter C EU: Guideline on Sterilisation of the Medicinal Products, Active Substance, Excipient and Primary Container

This guideline was published by the EMA in March 2019 and will enter into force on 1 October 2019.

Guidance is provided on the choice of sterilisation method, the development data and manufacturing data required to demonstrate the suitability of the selected sterilisation process. The importance of sterilisation in the final container, according to the reference conditions described in Ph.Eur., is highlighted as the preferred method. However, alternative methods are also being discussed, such as the use of sterile filtration or aseptic processing.

The optimal selection of a suitable sterilisation process is supported by decision trees, which are shown for

  • aqueous products
  • dry powder products, non-aqueous liquid or semi-solid products,
  • containers.

For new products, the document describes an appropriate assessment process and the requirements for the marketing authorisation application (or variation application) of a new or modified medicinal product. The focus is on risk assessment and risk acceptance in the overall context of quality risk management.

The guideline applies to chemical and biological medicinal products for human and veterinary use, but does not apply to immunological veterinary medicinal products.

Chapter D USA: CFR and FDA Guidelines


The Code of Federal Regulations is subject to an annual revision. With the current Update of the GMP Compliance Adviser we provide the actual versions as of April 1, 2019.

The dates of the following CFRs have been updated without any further amendments: D.1.1 to1.4 and D.1.5 to D.1.900

D.1.6 21 CFR 600

In 21 CFR Part 600 paragraph 21 titled Time of inspection was shortened.

D.19 Considerations in Demonstrating Interchangeability with a Reference Product

This guidance provides an overview of important scientific considerations in demonstrating interchangeability with a reference product, including the following:

  • Data and information needed to support a demonstration of interchangeability
  • Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
  • Considerations regarding the comparator product in a switching study or studies
  • Abbreviated considerations for developing presentations, container closure systems, and delivery device constituent parts for proposed interchangeable products

D.21 Questions and Answers on Biosimilar Development and the BPCI Act

This guidance document provides answers to common questions from prospective applicants and other interested parties regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).
The Q&A addresses a broad range of issues, including:

  • Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product (April 2015)
  • Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (April 2015)
  • Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product (December 2016)
  • Labeling for Biosimilar Products (July 2018)

G.2 Canadian Regulations

All links to the Canadian Regulations were updated.

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