GMP Compliance Adviser Update No. 2/2019

GMP Regulations

Chapter C EU Directives and Guidelines

C.8.2 Commission Delegated Regulation (EU) 2016/161

The Delegate Regulation (EU) 2016/161 on the so-called "Counterfeiting Directive" 2011/62/EU lays down mandatory safety features for the packaging of medicinal products for human use, which entered into force on 9 February 2019.
It implements a system which ensures the identification and authentication of medicinal products through end-to-end verification of all medicinal products bearing the security features. In addition, certain medicines with a higher risk of counterfeiting will be verified by wholesalers throughout the supply chain. In practice, the authenticity and integrity of the security features affixed to the packaging of a medicinal product at the beginning of the supply chain should be verified at the time when the medicinal product is released to the public, i.e. at the pharmacy. The two features necessary for medicine packaging are:

• a unique identifier for verifying authenticity in the form of a two-dimensional barcode.
• a device against tampering on the packaging (anti-tampering device) of certain medicinal products for human use to check their integrity.

Directive 2011/62/EU on the prevention of the entry of counterfeit medicinal products into the legal supply chain is part of Directive 2001/83/EC and can be found in Chapter C.8.

C.9 Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products

In line with Directive 2001/83/EC on medicinal products for human use, this directive lays down the rules relating to the manufacture, control and inspection of veterinary medicinal products. The Veterinary Medicinal Products Directive has been newly included for the purpose of completeness. The provided link will take you directly to the original document.

C.10.1 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices (EU MDR

C.10.2 Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices (EU IVDR)

The medical device industry has steadily grown over the past years. New advanced products entered the market and an adaption of the law was more than overdue. The new approach on the regulation of medical devices aims at ensuring a high level of protection of health for patients and users, taking into account the small-and medium-sized enterprises that are active in this sector. At the same time, it sets high standards of quality and safety for medical devices in order to meet common safety concerns as regards such products. The new regulations harmonise the rules for the placing on the market and putting into service of medical devices and their accessories on the Union market thus allowing them to benefit from the principle of free movement of goods. A 3-year transition period is granted and the regulation will fully apply on May 26, 2020 for the EU MDR and a 5-year transition for the EU IVDR. The most important changes introduced with the new MDR are:

• Clinical investigations and evaluations are regulated in more than 20 articles of the MDR
• Notified bodies (NB), manufacturers and importers will have to be registered (MDR certificate)
• The technical documentation (Annex II) must be updated continuously
• Labeling requirements have been massively increased
• Installation of a scrutiny procedure for NBs (class IIb and III devices)
• A Unique Device Identification (UDI) will be required
• Extension of the EUDAMED Database
• Access to competent authorities, manufacturers, NBs, and the public
• Display of certificates, vigilance reports, clinical investigations, PMCFs
• Harmonized evaluation of high-risk devices.

Chapter D USA: CFR and FDA Guidelines

D.22 Data Integrity and Compliance With Drug CGMP Questions and Answers Guidance for Industry

The guidance updates a draft version released in 2016. It covers the design, operation and monitoring of systems and controls to maintain data integrity. The document takes into account various aspects outlined in a parallel press announcement issued by FDA commissioner Scott Gottlieb. An increasing number of warning letters directly related to lack of data integrity is one of the issues he addresses. Often these deficiencies are the result of inadequate processes and systems, unfortunately often of misleading practices. However, he also points out new ways the FDA has taken, such as the MRA between the US and the EU on mutual recognition of GMP inspections, to increase the authority's reach in identifying violations of data integrity. The 17-page document is structured into 18 questions and answers which should be considered as “recommentations”.