News about GMP/cGMP

The EMA has just published a draft for a questions and answers paper on production of water for injections (WFI) by non-distillation methods. The Ph.Eur. monograph for WFI was revised to include, in addition to distillation, reverse osmosis (RO) coupled with suitable techniques, for the production of WFI.

From 4 to 8 July 2016, the MHRA hosted the following events in Manchester (UK): PIC/S Committee meeting, PIC/S Executive Bureau meeting, and PIC/S Annual Seminar.

The international hot topic of data integrity continues to develop. Eighteen months after releasing its GMP data integrity guidance, the MHRA (Medicines and Healthcare Products Regulatory Agency, UK) has now published a revision thereof. The draft document entitled GxP data integrity definitions and guidance for industrycomprises 14 pages and can be seen as the next phase of MHRA guidance.

WHO has recently issued a 21-page draft document “Guidelines on Validation” which covers the main principles of validation and qualification. The guidelines are not intended to be prescriptive in specific validation requirements but focus on the overall concept of validation. The principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs) as well as other areas. Validation of specific processes and systems, e. g. sterile product manufacture, are beyond the scope of the guideline.

FDA has published an 11-page draft guidance on elemental impurities that provides recommendations regarding their control in human drug products marketed in the United States. The draft document is set up in consistence with ICH Q3D, published in August 2015 by the ICH (International Council for Harmonisation). The FDA draft guidance intends to help manufacturers to comply with ICH and United Pharmacopeial Convention (USP) standards.

The International Council for Harmonisation (ICH) met in Lisbon, Portugal in June 2016. Two new members were accepted and 14 new observers welcomed.

The FDA has issued a 10-page technical specifications document providing recommendations on the submission of data to support quality metrics as part of the process validation lifecycle and pharmaceutical quality system assessment. The guide serves as the technical reference for implementation of the draft FDA guidance “Request for Quality Metrics” that was published in July 2015 and can be seen as a supplement.

Almost one year after publishing the draft, the WHO has now issued the final version of the Guideline to “Good Data and Record Management Practices”. The document is part of the Technical Report Series No. 996, 2016 and is therein listed as Annex 5.

With the U.K. voting to leave the EU, the speculation about a new headquarter for the European Medicines Agency EMA have started. The London-based EMA approves medicines for all EU countries. With a full-time staff of around 750, it is the largest EU body in Britain.

According to the US FDA, two Indian manufacturing facilities have been added to the Red List of foreign firms that are now banned from shipping product to the US. Cheryl Laboratories, Mumbai, producing active pharmaceutical ingredients (APIs) and Phalanx Laboratories, Visakhapatnam, producing APIs and intermediates both refused FDA inspections without giving any comment.

On 7 June 2016, Maas & Peither-GMP Publishing received a SIPAward in Washington, DC, USA, at the 40th SIPA Annual Conference. The GMP MANUAL was nominated out of 228 applications in the special category "Best New Success Story" and was awarded 3rd place. The GMP MANUAL is the world’s largest GMP knowledge database for the pharmaceutical industry and impressed the jury with “Save Drugs through Better GMP Understanding”. Prizes in a total of 25 categories were awarded.

From May 30 to June 7, 2016, the Ninth Annual International Internet Week of Action took place. This global cooperative effort, led by INTERPOL, aims at fighting the unlawful sale and distribution of illegal and potentially counterfeit medical products on the internet. The operation involved regulatory authorities, custom agencies and law enforcement form more than 100 countries.

In April 2016, the Transatlantic Trade and Investment Partnership „TTIP” , negotiated between the EU and the US, was taken one step further. The 13th round of negotiations took place in New York. The European Commission has now published a detailed report on the three negotiated areas market access, regulatory cooperation and rules. Furthermore the EU has released a 7-page EU-proposal for an annex on medicinal products containing details for the pharmaceutical sector.

The WHO has revised its Technical Report Series, No. 961, 2011, Annex 5: Supplementary guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms. A draft has been published for public consultation.

The European Commission is about to adopt an amendment to the Mutual Recognition Agreement (MRA) with Switzerland. The amendment would cover the mutual recognition of GMP inspections in third countries as well as products manufactured outside Switzerland.

The European Medicines Agency (EMA) has finalized a guidance that covers process validation including process characterization and process verification in the manufacture of biotechnology-derived active substances. This document provides guidance on the data to be included in a regulatory submission to demonstrate that the manufacturing process is in a validated state.

Another Indian drug maker received a warning letter issued by the US FDA. Once more the hot topic is data integrity – a common feature nowadays.

Data manipulation and data integrity issues are topics that constantly appear in the press. In recent years, cGMP violations involving data integrity have been increasingly observed, especially in China and India. This is troubling because ensuring data integrity is an important component of industry’s responsibility to ensure the safety, efficacy and quality of drugs. Following the MHRA and the WHO, that have both released draft documents on this subject in 2015, the US Food and Drug Administration (FDA) has now published a Draft Guidance on Data Integrity and Compliance with cGMP, as well.

The US Food and Drug Administration (FDA) approved a second biosimilar, Inflectra (infliximab-dyyb), biosimilar to Janssen Biotech’s arthritis treatment Remicade (infliximab). Inflectra, coming from Celltrion and Pfizer, is a monocional antibody biosimilar. The European Medicines Agency already approved Celltrion’s Remicade biosimilar in 2013. Other countries that already gave their approval are Canada, Japan and Korea.

Following the three final guidances on quality considerations, scientific considerations and Q&As about biosimilars, the FDA has now released a 15-page draft guidance for industry on Labeling for Biosimilar Products. The guidance provides an overview of FDA’s recommendations for biosimilar product labeling and is intended to assist industry in developing draft labeling for submission in proposed biosimilar product applications.

21 March 2016 marked the date on which Manufacturing Authorisation Holders (MAHs, also known as pharmaceutical product manufacturers) needed to be compliant with the “Guidelines of 19 March 2015 on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use”. IPEC Europe has developed and published a 36-pages "How-to" documentto help explain how a company might perform a risk assessment to determine the appropriate GMPs necessary for each excipient they use in drug products.

On 9 March 2016, a meeting of the EU-China Working Group on Pharmaceuticals was held in Beijing. A delegation of the CFDA met with Andrzej Rys, Director of DG Sante of the European Commission and Guido Rasi, Executive Director of the EMA (European Medicines Agency).

The Central Drug Standard Control Organization CDSCO of India has published a new Guideline on Similar Biologic. The 58-pages document will replace the previous guidance issued in 2012. The new version is now open for discussion until April 30, 2016.

The European Commission has published a revised Version 6 of its Question and Answers Document that sets out frequently asked questions on importation of active substances for medicinal products for human use.

During its 154th Session, the Ph. Eur. Commission adopted a revision of its monograph for Water for Injections (0169). Up to now, the production of Water for Injections (WFI) had been limited to distillation only.

The revised Annex 1 on sterile and aseptic production of the EU GMP Guide is expected to appear this autumn. The draft will be discussed soon in the EMA IWG and the PIC/S. Afterwards it will proceed as an approved draft to public consultation. The document will be completely revised without being restricted to isolated improvements.

According to Andrew Hopkins, MHRA, the new ISO 14644:2015 will be given a 12-month period for implementation. This was explained during the introduction of the contents of the new Annex 1 at a conference in in Frankfurt.

The European Pharmacopoeia envisages the production of water for injections (WFI) in Europe as well with the aid of reverse osmosis. Susanne Keitel, EDQM, reported in Frankfurt that the decision is expected to be made this week.

The U.S. Food and Drug Administration (FDA) announced the confirmation of Dr. Robert Califf, M.D., as next commissioner of the FDA. He fills the position left by Dr. Margaret Hamburg, who stepped down after six years as commissioner.

The International Council on Harmonization (ICH) has published eight training modules on the ICH Q3D Guideline Elemental Impurities. These modules are part of a comprehensive training programme prepared by the ICH Implementation Working Group.

From 21 March 2016 onwards, the new requirement of the Guidelines on the formalized risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use enter into force. These guidelines are part of the EU GMP-GUIDE Part III and were published in their final version a year ago. Basically, the manufacturing authorisation holder is obliged to ensure that the excipients used are safe for drug manufacturing and that an appropriate level of GMP-standards has been applied.

On 9 February 2016 the European Commission published the Delegated Regulation 2016/161 in its Official Journal. The document sets out the details of obligatory “safety features” for the packaging of medicinal products for human use.

Counterfeit drugs are a major threat to public health. Current efforts to guard against counterfeit medicines often focus on serialization of the secondary packaging which - while providing a substantial improvement in patient safety - does not allow tracing of the individual unit.

The U.S. Food and Drug Administration (FDA) published the yearly list of new and revised draft guidances, CDER is planning to publish in 2016. A total of 102 planned guidance documents are set out. There are a couple of carry overs from 2015, e. g. documents on the drug supply chain security act, on biosimilars or two guidances in the field of GMP.

The WHO has listed a revised guideline WHO GMP for Biological Products which was adopted by the 66thMeeting of the WHO Expert Committee on Biological Standardization. The document is proposed to be published in its final editorial form in the next WHO Technical Report Series.

On 1 January 2016, the Pharmacy and Poisons Board of Hong Kong SAR (PPBHK) as well as the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) became the 47th and 48th PIC/S Participating Authorities.

According to the ICH, the Australian Therapeutic Goods Administration (TGA) has become the latest ICH Observer. In this position the TGA is now allowed to attend ICH Assembly meetings and to participate in ICH activities.

EMA has published the work plan of the GMP/GDP Inspectors Working Group for 2016. The plan covers the different tasks of the group, e.g. harmonisation of inspections, mutual recognition agreements (MRAs) (maintenance, extension of scope) and GMP/GDP topics.

According to pharmabiz.com the WHO expressed strong interest in setting up a centre of excellence (CoE) in regulatory science at the Indian Gujarat FDCA’s (Food and Drug Control Administration) office. This will be the first Asia-Pacific-CoE of the WHO. If things go as planned, all the financial and technical support will be given by the WHO while the state government of Gujarat will provide infrastructural support within the FDCA’s building.