GMP Compliance Adviser Update No. 2/2017

With this GMP MANUAL 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

4.A Facility Planning


13.A.8 Packaging material testing

GMP Regulations

D.24 Guidance for Industry:
Contract Manufacturing Arrangements for Drugs: Quality Agreements
H.18 WHO: Good trade and distribution practices for pharmaceutical starting materials
(Technical Report Series, No. 996 (2016), Annex 6)

GMP in Practice

Chapter 4 Facilities and Equipment

4.A Facility Planning

Facility planning is very important when a facility is being procured. During this phase, all aspects of its later use must be taken into consideration and reflected in the facility requirements. The following must be taken into consideration: qualification procedures, requirements for materials and building and construction elements, hygiene requirements, cleaning capability, ease of servicing and maintenance, risks identified during manufacturing and cleaning processes, requirements for modern manufacturing methods, ease of use, etc. A comprehensive and detailed implementation of this phase ensures an efficient overall project. In this context, risk management is a key factor.

4.B Materials

Materials for the construction and assembly of equipment, especially in the case of product contact materials, should be selected such that there are no undesired interactions with the product. This requires that knowledge of influential parameters is available. Product properties also have an influence on the material selection and should therefore be described in advance. Stainless steel plays a key role in the manufacture of pharmaceutical equipment. Depending on the application, various types of stainless steel are available. Plastics also play a decisive role in equipment construction, especially in the realm of sealing technology. When using plastics the legal regulations concerning foodstuffs are to be followed. Lubricants also belong to the adjuvants used in equipment construction. Since contact with the products in the equipment cannot be completely ruled out, the requirements placed on lubricants are especially high. In the pharmaceutical industry only registered and certified lubricants may be used. These are included in white lists from the FDA and NSF. The regulatory requirements placed on sealing materials are also oriented by and large according to foodstuff legislation. When selecting an appropriate sealing material, flexibility and solvent resistance are important criteria.

Chapter 13 Packaging

13.A.8 Packaging material testing

The quality of primary and secondary packaging materials has to be tested prior to use. Testing the primary packaging materials is a major challenge for the medicinal product manufacturer because of the range of special methods used, and is therefore normally carried out by the packaging materials manufacturer. This requires qualification of the supplier and a contractual agreement. The medicinal products manufacturer then only needs to carry out reduced testing as part of the incoming goods inspection. Testing of secondary packaging materials is based on documents contractually agreed with the supplier. The defect evaluation lists with AQLs also play an important role. Examples of tests carried out on folding cartons, package inserts and labels are given.

GMP Regulations

Chapter D

D.24 Guidance for Industry: Contract Manufacturing Arrangements for Drugs: Quality Agreements

This long awaited guidance describes FDA’s current thinking on defining, establishing, and documenting manufacturing activities of the parties involved in contract drug manufacturing subject to CGMP requirements. It lays down quality management principles to carry out the complicated process of contract drug manufacturing to ensure the quality, safety, and effectiveness of drugs. Compared to the draft document which was released in May 2013, the FDA has now clarified that the guidance is limited to commercial manufacturing activities. Furthermore, the key terms “owner” and “contract facility” were clearly defined.

Per FDA's recommendations, the quality agreements should contain at least the following sections:

  • The purpose and scope of the contract agreement
  • The terms of the agreement, including its effective dates
  • Terms for dispute resolution
  • Responsibility of each respective party, including an overview of the subparts of the CGMP regulations
  • Change control and revision practices.

The 16-page guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115).

Chapter H

H.18 WHO: Good trade and distribution practices for pharmaceutical starting materials (TRS No. 996, 2016, Annex 6)

The scope of this WHO guidance is applicable to any ingredient that is used in the manufacture of a medicinal product, including APIs, excipients and any others.

Within an organization quality assurance is used as a management tool. In contractual situations, quality assurance also serves to generate confidence in the supplier. There should be a documented quality policy. The quality policy should clearly indicate that the distributor implements and maintains good trade and distribution practices (GTDP) as described in these guidelines, within the organization and its services. Besides the aspects of quality management the following areas are addressed:

  • Organization and personnel
  • Premises and equipment
  • Procurement, warehousing and storage
  • Documentation
  • Repackaging and relabelling
  • Complaints, recalls, returned goods and handling of non-conforming materials
  • Dispatch and transport
  • Contract activities.