GMP Compliance Adviser Update No. 7/2020

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 0

Current topics


0.A Nitrosamines
0.A.1 Information on nitrosamine impurities
0.A.2 Nitrosamine impurities in medicines: What
have we learned? – EMA report 2020
0.A.3 Unpacking FDA's new guidance on controlling
nitrosamine impurities in drugs


Chapter 4

Facilities and Equipment

4.I Containment (personnel protection) for APIs,
solid oral dosage forms and bio-pharmaceutical


Chapter 13


13.B Packaging process  

GMP Regulations

Chapter C 

EU Directives and Guidelines

C.8.2.1 Safety features for medicinal products for human use – Questions and Answers – Version 18

C.19 Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products


GMP in Practice

Chapter 4 Facilities and equipment

4.I Containment (personnel protection) for APIs, solid oral dosage forms and bio-pharmaceutical products

The term “containment” is used in the API, pharmaceuticals and bio-pharmaceuticals industries to describe die enclosure of a process in which highly active substances are produced or handled. Containment has a dual role in its function serving both to ensure occupational safety for the operator and also protection of the product.

Containment systems may be divided into categories according to their workplace exposure limit. The connection between OEB (occupational exposure band), OEL (occupational exposure limit) as well as PDE (permitted daily exposure) and ADE (acceptable daily exposure) is illustrated in the containment pyramid. Here, the OEB corresponds to the containment grade OEL corresponds to the particle concentration in the workplace air and the PDE & ADE refer to the permitted amount which can be taken in by the operator or patient.

The effectiveness of the containment is checked by means of occupational safety control measurements. Special filter devices and measuring systems are positioned close to the operator and the containment system and evaluated after a defined exposure time.

The protection of the operator can be ensured in the simplest case by personal protective equipment. Laminar flow systems offer protection for employees, product and environment. Isolator systems offer the most comprehensive protection.

Isolators consist of a stainless steel housing with transfer systems for the inward and outward transfer of products, a glass panel with glove openings for the operator, as well as supply and exhaust air filters.

Apart from the use of isolators there are further constructive possibilities to realize containment. Various filling, emptying and transfer systems for drums, containers and containers are presented. The containment can be achieved by mechanical de-signs as well as by the use of protective foils.

Single-use systems represent another alternative. Different application possibilities are presented, and the costs compared with isolator systems.

As a technology of the future, process-integrated containment is presented using the example of a fluid bed granulator. This method offers many advantages but is not yet used in routine production.

Finally, the planning and design of a containment plant is presented using a case study for the production of active ingredients. During the planning phase, attention should also be paid to possible weak points that could later lead to deficiencies in operation. This concerns the change of filters, cleaning, maintenance and servicing, for example. (Richard Denk)