GMP in practice

Chapter 11 Production

This chapter has been completely reviewed by Paolomi Mukherji. The requirements concerning production hygiene, especially environmental monitoring, were updated to reflect the current provisions of the revised Annex 1 to the EU GMP Guide, along with US requirements and ISO Standards. Besides production and personnel hygiene, the chapter describes GMP-critical processes within the large field of production, e.g. weigh-in, labeling, in-process control, rework, cross-contamination and warehousing. A lot of examples are given showing systematic approaches to set up procedures and implement systems like reconciliation, pest control or warehouse control. This chapter is indispensable for all who work in the field of pharmaceutical manufacturing.

Chapter 19 Quality Unit

This new chapter replaces the chapter “Tools for Quality Assurance” and will focus on the tasks and responsibilities of a Quality Unit. The first contribution to this chapter deals with the duties and responsibilities of a “Qualified Person” in the light of Directive 2001/83/EC. It describes the Qualified Person’s place in the hierarchy of a company and the basic requirements for this function. Differences between certifying investigational medicinal products compared to marketed drugs are highlighted. Last but not least the “Discretion” of the Qualified Person to release batches that do not comply with the marketing authorization is discussed. This chapter was written by Bernd Renger.

Chapter 20 Continual Improvement Methods

This new chapter is dedicated to concepts and methods which focus on continual improvement of quality although not being regulatory requirements for the GMP-related industry. It describes approaches that are already successfully used in other industry branches, like Six Sigma or Kaizen, and shows how these approaches can be adapted to pharmaceutical industry. Commonly used methods and tools like FMEA, SPC or Pareto Charts will be presented later on. The chapter is referencing to ICH Q10 “Pharmaceutical Quality System” where the concept of continual improvement is described. Chapter 20 will be opened with a preface by Thomas Peither and a very comprehensive chapter on Six Sigma written by Rolf Staal.

GMP regulations (File 4–5)

Chapter C EU GMP Guide

• C.1       Introduction
  The introduction was updated to include references to quality risk management following the inclusion of Annex 20 Quality Risk Management. With this Update you receive the actual version dated
  12 February 2008.
• C.6.3    Annex 3 Manufacture of Radiopharmaceuticals
  This annex has been revised in the light of new GMP requirements for active substances used as starting materials (GMP Part II) and updated for all relevant aspects of GMP for radiopharmaceuticals. The Deadline for coming into operation was 01 March 2009.
• C.6.7    Annex 7 Manufacture of Herbal Medicinal Products
  The annex has been revised to specify the application of GMP provisions for active substances used as starting materials (Part II) for the manufacture of herbal medicinal products. Additional changes are in particular related to the new Directive 2004/24/EC on traditional herbal medicinal products. The date of revised version coming into operation is 01 September 2009.
• C.10     Compilation of Community Procedures
  The compilation of community procedures on inspection and exchange of information encompasses procedures and forms relevant for inspections, which are approved by inspectorates of all Member States. They are intended to facilitate the administrative cooperation as well as harmonization and exchange of information related to inspections. According to article 3 of Directive 2003/94/EC Member States are obliged to follow these community procedures and to take them as a basis for the establishment of procedures within the quality systems of the inspectorates.

Chapter E ICH Guidelines

• E.8       ICH Q8 (R1) Pharmaceutical Development
  Together with the adoption of step 4 of the Annex to ICH Q8, the guideline was revised. The new ICH Q8(R1) consists of Part I (Parent guideline) and Part II (Annex to the Parent guideline). Although most of the annex remained unchanged, some formulations were rendered more precisely and the term “Quality Target Product Profile” was newly introduced.
• E.1.D    ICH Q1D Bracketing and Matrixing Designs for Stability Testing of new Drug Substances and Products
  This guideline is intended to address recommendations on the application of bracketing and matrixing to stability studies conducted in accordance with principles outlined in the ICH Guideline Q1A(R) “Stability Testing of New Drug Substances and Products”.
  It provides guidance on bracketing and matrixing study designs. Specific principles are defined for situations in which bracketing or matrixing can be applied.
• E.1.E    ICH Q1E Evaluation for Stability Data
  This guideline is intended to provide recommendations on how to use stability data generated in accordance with the principles detailed in the ICH guideline Q1A(R) “Stability Testing of New Drug Substances and Products” to propose a retest period or shelf life in a registration application. This guideline describes when and how extrapolation can be considered when proposing a retest period for a drug substance or a shelf life for a drug product that extends beyond the period covered by long-term data.

Chapter F PIC/S Guidelines

• In September 2008 the PIC/S published new versions for all Guides and Recommendations to reflect changes in the editor’s coordinates. You will receive the updated pages of chapters F.1 –F.6 with this supplementary set.
• F.2       PIC/S PI 007 Recommendation on the Validation of Aseptic Processes
  The recent version 5 came into operation on 01 July 2009. Chapter 6 of the document was completely revised in accordance with Annex 1 to the EU GMP Guide. Changes in the former version 4 related to chapter 5.3 Incubation methods.

Chapter G GMP of other regions

• G.1.1    WHO Quality Assurance of Pharmaceuticals
  This very comprehensive GMP document which applies to most countries world-wide is delivered on the CD / Online version only.

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