In March 2020, the EQPA surveyed its members on the topic of batch certification performed by a QP whilst not physically present at the site of
the manufacturer, or “Remote QP Certification”. The topic was perceived as an area of non-harmonised national interpretations and the EQPA sought to better understand the differences across the European Union (EU)/European Economic Area and on how QPs positioned themselves in such a procedure.
The survey was launched shortly after the UK’s Medicines and Healthcare Product Regulatory Agency (MHRA) published views on the topic by way of its inspectorate blog in February 2020. At that time, the COVID-19 pandemic was rapidly spreading across Europe and public health bodies were promoting remote working where possible, in order to avoid unnecessary contact.
Survey and results The survey, responded to by more than 300 QPs, revealed an interesting pattern of approaches. As would be expected, the responses reflected the perceived expectations of their respective national authorities
and/or their understanding of national law. QPs acting in a generally acceptive environment for remote QP certification were much better equipped to answer
the questions posed in the survey than those who believed that their national law would not allow it. The EQPA believes that neither the EU Guidelines for
Good Manufacturing Practice (GMP) nor Directives 2001/8(2)3/EC require the
physical presence of the QP at the manufacturing site during certification. However, in several member states such physical presence is enforced, either
clearly through national law, or less clearly, by the interpretation of law by national authorities. An argument for the QP’s physical presence on site is that
the responsibilities of the QP can be met in full only through a high level of continuous interaction with manufacturing operations. Another known
argument is that QP certification, being an integral part of GMP regulation, can only be executed at the listed premises of the Manufacturing/ Import Authorisation Holder.
The EQPA was interested in whether rules might change in the face of a pandemic. It did not know how many QPs already had the freedom to exercise remote QP certification in their local environment. In this respect, the survey revealed an even split with almost 50% of QPs aware, at the start of the COVID-19 pandemic, that remote QP certification would not be an option on their territory.
This is an extract of an article by by Ulrich Kissel and David Cockburn from Industrial Pharmacy Issue 68 Subscribe to the IP
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Introduction
During an audit, the auditor needs to collect evidence that confirms that the information produced by the management is accurate. It is not possible for an auditor to examine and physically verify everything within the pharmaceutical or healthcare facility; instead, a snapshot needs to be taken in order to gain sufficient audit evidence. Audit evidence includes written and electronic information that permits the auditor to reach conclusions through reasoning, and this rests on the appropriateness of the sample taken. How representative the snapshot is can be enhanced through the application of different techniques. The audit cannot run on indefinitely and so the auditor will need to maximise the time available. Hence, time will always be the enemy during an audit. Any activity which makes the audit more efficient or can save time is worth pursuing, and good questioning technique forms part of this. There are different techniques and methodologies aimed at auditing, some of which will be more suitable to different situations than others. This article considers some of the different auditing models that can be applied.
Interviewing techniques
Interviews are a key part of the audit process. They are an important way of obtaining and confirming information and facts about the way systems and controls are being operated. At the same time, they represent an opportunity to create and maintain good relations between the auditors and the clients, and to impress the client with the professionalism of the audit. There is no ‘best’ method of interviewing. The approach depends on the person being interviewed, the nature of the audit, the type of information needed and the time available. There are two types of interview – directive and non-directive.
To read more of this article subscribe to the GMP Journal and request a complimentary back copy of Vol 19 No. 4
Article by Tim Sandle
]]>In the context of a global business with ever-increasing quality standards and effectiveness requirements as well as the latest draft review of the Good Manufacturing Practice (GMP) Annex 1 of December 2017, one of the main technical areas explored is related to studying and mitigating potential process/product contamination risks against biological bodies, particulates and pyrogen agents. One key strategy for cleanroom supervisors should be to carry out complete Risk Assessments in order to map, classify, and then reduce contamination risks.
Humans are the main source of potential contamination inside cleanrooms
(more than 70%), as shown by several past global studies (Akers, J. et al., 2004; Ramstorp M, 2000 and Whyte and Hejab, 2007). Hence, cleanroom garments serve as the last protection barrier against controlled environment contamination by the thousands of human particles (potentially carrying microorganisms) that are shed every minute. In terms of contamination risk management, it is critical to evaluate the variables related to human contamination and cleanroom garment barrier performance besides HEPA filtering, process air flow velocity and other factors. This study aims to explore several important technical aspects of cleanroom garments that should be considered when evaluating contamination risks.
The process of wearing, laundering and sterilizing reusable cleanroom garments can impact their physical properties and change their functionality.
Laundering and wearing abrades garment fibres. Simultaneously, changes to the polymers that make up the garments can occur at the molecular level. Although routine visual inspection is often part of garment quality evaluation programmes, non-visible properties also change with time.
When selecting reusable garments for use in cleanroom environments,
it is important to understand how they will perform over their intended life
cycle. Consideration of all the degradation aspects should be part of the decision process for when to take reusable garments out of service, or alternatively to change to a single-use garment system. Several factors should also be considered when evaluating intrinsic risks generated by cleanroom garments, such as: particle shedding, biological/ particle barrier, worker comfort and protection, durability, packaging, sterilization continuous validation –
besides process and supply factors: logistics chain reliability, damages and
repairs, shrinking and ergonomic fit, among others.
This is an extract of an article from CACR Issue 38. To read more of this article and others like this subscribe to the quarterly CACR
Article by Matheus Barbosa, Jean-François Teneul
]]>Introduction
The announcements from Pfizer/BioNTech and from Moderna early in November of the very positive efficacy data from their mRNA COVID-19 vaccine trials heralds not only the advent of vital weapons in the global fight against the pandemic but opens up the possibility of using new technologies in other infectious diseases such as influenza. In addition, the US FDA’s Emergency Use Approval of Eli Lilly’s neutralising monoclonal antibody LY-Cov555 (Bamlanivimab)and Regeneron’s antibody combination product (Casirivimab and Imdevimab) adds to our anti-COVID-19 armamentarium. The speed at which these developments have occurred is remarkable and without precedence in the history of drug discovery and development. Eli Lilly’s antibody took only 52 days from donor blood samples to GMP manufacture and 3 months to first patient entry.
These advances and many more ongoing developments are the result of truly excellent new partnerships between the pharma and biotech industries, academic and government research institutes and, importantly, the willingness of Regulatory Agencies to provide guidance and clear pathways to data review. Many companies have prioritised COVID-19 R&D against their other portfolio programmes and projects and in doing so have restructured their activities to include such features as parallel processing, accelerated digital systems, delegation of decision making and distant clinical trials; features that will probably increase the efficacy and effectiveness of their overall R&D efforts going forward.
This is an extract of an article by Trevor M Jones from Industrial Pharmacy Issue 67. Subscribe to the IP here
]]>Professor Martini is a registered practising Industrial Pharmacist and a Fellow of the Royal Pharmaceutical Society. Professor Martini also divides his time between the RPS and King’s College London as a Visiting Professor in Pharmaceutical Innovation, after having held the Chair in Pharmaceutical Innovation at King’s for 5 years. Professor Martini is also Visiting Professor at the University of Bradford.
Prior to his tenure in Academia, Professor Martini spent over 17 years working at GlaxoSmithKline Pharmaceuticals, Roche Products Ltd and Shire Pharmaceuticals working in a variety of Technical, Commercial, Innovation based and Medical Affairs roles, directing groups in the US, Europe and Emerging Markets.
Professor Martini has an MBA specialising in SME success and business failure awarded with Distinction from the University of Liverpool.
Professor Martini is past Chair of the Industrial Pharmacists Group of the Royal Pharmaceutical Society and past President of the European Industrial Pharmacists Group.
In 2016, Professor Martini was appointed a Fellow of the European Industrial Pharmacists Group.
]]>Tim brings a lot of experience and expertise to his new role. He is the Head of Microbiology at the UK Bio Products Laboratory. His role involves overseeing a range of microbiological tests, batch review, microbiological investigation and policy development
]]>Dr Tim Sandle is the new editor of our journal GMP Review and follows in the footsteps of previous distinguished editors John Dolman, Kate McCormick and Peter Savin.
Tim brings a lot of experience and expertise to his new role. He is the Head of Microbiology at the UK Bio Products Laboratory. His role involves overseeing a range of microbiological tests, batch review, microbiological investigation and policy development. In addition, Tim is an honorary consultant with the School of Pharmacy and Pharmaceutical Sciences, University of Manchester and is a tutor for the university’s pharmaceutical microbiology MSc course. Tim is a chartered biologist and holds a First Class Honours Degree in Applied Biology; a Master’s degree in Education; and a PhD in the safety testing of blood products. He has been involved over many years in the whole area of Quality Assurance.
Tim serves on several national and international committees relating to pharmaceutical microbiology and cleanroom contamination control (including the ISO cleanroom standards). He has acted as a spokesperson for several microbiological societies. He is a committee member of the UK and Irish microbiology society, Pharmig and is editor of its newsletter. Tim has written over 450 book chapters, peer-reviewed papers and technical articles relating to pharmaceuticals, cleanrooms and microbiology; these include co-editing the books Industrial Pharmaceutical Microbiology: Standards & Controls, Cleanroom Management in Pharmaceuticals and Healthcare and Pharmaceutical Regulatory Inspections. He is currently finalising an essential new book, Antimicrobials and Biotechnology: Global concerns and future strategies to be published later this year.
Also, Tim runs an on-line microbiology blog (www.pharmamicroresources.com).
]]>Authentication of medicines under the Falsified Medicines Directive (FMD) [Directive 2011/62/EU and Delegated Regulation 2016/161] started across 32 Member States of The European Union (EU) and European Economic Area (EEA) on 9th February 2019. This followed a hectic three-year implementation period during which an entire system of interconnected European and national databases was developed, pharmacies and wholesalers upgraded their internal systems and processes, and manufacturers began serialising billions of individual prescription medicine packs.
FMD is not a "track and trace" system. Instead, it was developed on the "bookends" principle. Unique identification codes are produced and uploaded by manufacturers at one end. These codes are verified and decommissioned when the packs leave the supply chain at the other end. The decommission is normally undertaken by the community or hospital pharmacies as part of the dispensing process, but can also be undertaken by dispensing medical practices, pharmaceutical wholesalers (in some circumstances) and a range of other healthcare institutions that supply medicines to patients.
The aim of FMD is to make it more difficult to introduce falsified products into the European medicines supply chain. Serialised packs and a process of verification and decommissioning should help identify any potentially falsified products before they reach patients. The introduction of machine-readable barcodes on all packs should also help with stock ordering, stock rotation, accuracy checking, product recalls and reimbursement.
This is an extract from an article by Jonathan Buisson from the Industrial Pharmacy Journal Issue 61, to read more subscribe now.
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Sterile manufacturing is a continuum that stretches from development to manufacturing, to finished product; and to marketing and distribution, as well as the utilisation of drugs and biologics in hospitals and in patients’ homes. Although the terms ‘sterile manufacture’ or ‘aseptic manufacturing’ are widespread, there is no generic approach to the manufacturing of sterile products. Each plant or process will differ in relation to the technologies, products and process steps.
The preparation and operation of regulatory inspections represent an important part of the biannual or annual cycle for pharmaceutical organisations. With sterile products, the main hazards are viable microorganisms, particulate matter (particles which may or may not be microbial in origin), and microbial by-products, especially pyrogens.
As Section III of the USA Food and Drug Administration (FDA) guidance on sterile products notes: “Nearly all drugs recalled due to non-sterility or lack of sterility assurance in the period spanning 1980–2000 were produced via aseptic processing.”
Such trends are also reflected in outcomes reported by other regulatory agencies, such as the UK Medicines and Healthcare Products Regulatory Agency (MHRA). This is the first in a series of articles that attempts to present an overview of the general topics relating to the manufacture of sterile products and to outline some of the more important aspects which the manufacturer should review and prepare for prior to a regulatory inspection by a body like the FDA, a European inspector (as required by the European Medicines Agency) or by the World Health Organization. These selected topics are what we consider to be the ‘focal points’, and they reflect the deficiencies most commonly cited by regulators.
This is an extract from an article by Madhu Raju Saghee, Tim Sandle and Palash Das from GMP review Vol. 17 No. 2, to read more subscribe now.
]]>After providing a review of current and emerging regulations and standards, the article proposes a risk and science-based quality-by-design approach for the development, implementation and validation of sterile cleanroom garment systems. With this approach, more effort is spent at the front-end during the design phase as well as during design qualification. This will lead to designed-in risk reductions, enhanced scientific knowledge on selected technical solutions and better awareness of limitations and residual risks. As a result, there should be fewer issues during cleanroom qualifications and process validations leading to more effective routine operations as well as improved patient safety. The proposed approach, if implemented correctly, is not only the correct strategy to effectively control contamination risks related to people but also an adequate response to the latest regulatory requirements,
This is an extract from an article by Milenko Pavicic and Thierry Wagner in the Cleanroom and Containment Review (CACR) issue 39, to read more subscribe now.
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