Figure 2 - uploaded by Alan R Thornhill
Content may be subject to copyright.
The ‘Deming’ or ‘PDCA’ cycle is a rolling circle of four compartments; Plan, Do, Check and Act. Plan, establish objectives and identify the necessary processes to achieve them; Do, implement the new processes; Check, measure and compare the results against the expected outcome; Act, analyse any differences and the level of performance, if necessary, repeat the PDCA cycle.
Source publication
Accreditation according to an internationally recognized standard is increasingly acknowledged as the single most effective route to comprehensive laboratory quality assurance, and many countries are progressively moving towards compulsory accreditation of medical testing laboratories. The ESHRE PGD Consortium and some regulatory bodies recommend t...
Context in source publication
Context 1
... PGD laboratories, this concerns principally the interactions with the IVF clinicians, who may need advice and guidance in preparing for testing or in future planning. There is an overlap with the contribution to patient care mentioned in ISO 15189 section 4.12.4. Peter Drucker (1909–2005), one of the pioneers of modern management, stated that ‘Quality in a service or product is not what you put into it; it is what the customer gets out of it’. ISO 15189 reflects this by the requirement for the laboratory to develop a system to record and resolve feedback from clinicians, patients or other parties. Although it is a formal requirement to record and resolve complaints, it is recommended to extend the system to include positive feedback and requests for information. Such information provides a valuable quality indicator and can contribute to continual improvement. If, for example, there are many identical telephone requests (‘what is your fax number?’), it is clear that the lab is not providing the information appropriately to its users. The simpler the registration system, the higher the chance is of regular usage by personnel and, in turn, of obtaining a comprehensive overview. Figure 1 shows an example form, in use for many years in an accredited molecular genetics laboratory; copies are kept next to all telephones, and the form is widely used and easily analysed. Centres should regularly review user satisfaction with their services by actively seeking feedback, although this is not a formal requirement of ISO 15189 (section 4.8). In the case of PGD, this concerns principally the IVF unit(s) with whom they work, but—according to the organization—may also include other medical professionals and patients. For local IVF centres, this can be achieved through regular meetings; an agenda should be circulated to all staff, both teams should have free access to add important issues to the agenda and minutes must be taken and followed up at the start of each meeting. Meetings may not be practical for other users, notably in the case of transport PGD; in such cases, a questionnaire-based user-satisfaction survey can be used. User satisfaction is an important element of the management review (see ISO 15189 section 4.15). These elements can be confusing to newcomers to quality management; however, when successfully implemented, they provide some of the major benefits to the laboratory. ‘Non-conformity’ (also known as non-compliance) exists when any aspect of the laboratory’s activity is identified as not conforming with its own procedures or with the agreed requirements of the requesting clinician or the QMS. The laboratory is required to react to the non- conformity. This typically initially involves ‘corrective action’ to elimin- ate or reduce the effect of the non-conformity. In the case of ‘critical’ non-conformities, which may have an impact on patient care, the corrective actions may need to be performed urgently; it may also be necessary to suspend the activity in question, to avoid any risk of recurrence. Following the immediate corrective actions, the root cause should be identified. If there is a risk of recurrence (which is almost always the case), appropriate ‘corrective actions/preventive actions (CAPA)’ should be designed and implemented. A follow-up audit should be planned to ensure that the CAPA was effective (that is, had the desired effect) and efficient (effective without an excessive increase in workload). As with suggestions and complaints (ISO 15189 section 4.8), the initial registration of non-conformities should be simple and accessible to all personnel; the results should be rapidly transmitted to and analysed by appropriate staff. A simple procedure should also exist to encourage the proposal of preventive actions before the detection of non-conformities, for example, by way of a ‘suggestions box’. An important route to and indicator of the successful implementation of a QMS is the clear distinction between ‘non-conformity’ and ‘blame’. The identification of a non-conformity is almost always a sign of a fault in the system, rather than a fault or error by an individual. Personnel should be encouraged to identify and react to non- conformities, but discouraged from denouncing individual people. A ‘blame culture’ discourages reactions to problems and severely impairs the possibility of quality improvement. Quality improvement is both a formal requirement and a natural outcome of ISO 15189, based on regular audit and review of procedures, training for personnel and users, CAPA, and any other appropriate mechanism. A successful QMS is dynamic and will evolve to better meet the needs of users (improvement of quality, efficacy) and to reduce the workload on personnel (efficiency). The system must therefore be regularly or continuously evaluated to identify areas for improvement. The quality improvement cycle was famously described by Deming (Fig. 2). ISO 15189 section 4.12.4 requires that ‘Laboratory management shall implement quality indicators for systematically monitoring and evaluating the laboratory’s contribution to patient care’. Quality indicators are a common source of bemusement to newcomers but in fact represent a valuable tool not only in measuring improvement in lab performance, but also in demonstrating these improvements, to staff, users and management alike. As usual, the standard requires the implementation of quality indicators but does not impose a specific solution or a list: this must be produced by each laboratory according to its activities. Quality indicators should be developed to cover as much of the laboratory’s activity as possible, including both technical and management aspects. Quality indicators have to be SMART: specific, measurable, achievable, relevant, time-bound. Therefore, for each quality indicator, it needs to be documented how and how often it is going to be measured, what are the limits and what happens if the limits are not met. For example, the PCR contamination rate is a quality indictor that could be measured every 10 cases with a limit of less than 5%. If this limit is exceeded, the PCR team would need to determine why this limit is being exceeded. Quality indicators will typically be analysed for and presented at the Annual Management Review (see ISO 15189 section 4.15). Labs are recommended to develop systems for collecting data on an ongoing basis, to ensure a constant overview and to simplify analysis and reporting. Table IV provides examples of quality indicators which can be useful or can be easily adapted to different ...
Similar publications
In conformity with Italian Law 273/91, IMGC, IEN and ENEA provides for traceability to the standards of the different quantities all over the country, so as to allow high-quality measurements and tests to be made.
At the European level, in the field of calibration and testing, Italy is active particularly within the European cooperation for the Acc...
The scope of this paper is the description of an interlaboratory comparison programme for extremely low frequency (ELF) electromagnetic fields (EMF) measurements performed at the High Voltage Laboratory of the National Technical University of Athens. The programme was organised in two stages in an exposure environment similar to that of electric po...
The aim of the study was to assess the rate of acceptance of preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis in Lebanese women with previously affected children with homozygous beta-thalassemia.
Women with a previously affected child attending a non governmentally funded thalassemia care center between 1 June 2005 an...
The implementation of Quality Management Systems in laboratory environment is being an increasing necessity, due to customerdemand for reliable and traceable test results.The General Coordination for Accreditation of Inmetro (Cgcre/Inmetro) is the Brazilian body responsiblefortheaccreditation of laboratories according to ISO/IEC 17025standard, and...
The importance of the metrology function at Philip Morris Europe (PME), a multinational organisation producing at over 40 sites in the European, Middle Eastern and African Regions is presented. Standardisation of test methods and equipment as well as the traceability of calibration gauges to the same reference gauge are essential in order to obtain...
Citations
... Training programmes facilitate progress towards certification both by supporting development of essential knowledge and competencies and by promoting a shared understanding of roles, responsibilities and the purpose of the GLP certification project. We found that for the substantial amount of training that could be delivered internally, training that was regular, practical and highlighted the benefits of GLP certification served to reduce errors, building new habits, and increasing engagement, reflecting experiences in other capacity strengthening programmes [25][26][27][28][29][30]. Specific GLP training could only be provided internally once some staff had undertaken IVCC-funded external training, particularly on SOP development, data management, GLP principles and quality assurance. ...
Background
Insecticidal mosquito vector control products are vital components of malaria control programmes. Test facilities are key in assessing the effectiveness of vector control products against local mosquito populations, in environments where they will be used. Data from these test facilities must be of a high quality to be accepted by regulatory authorities, including the WHO Prequalification Team for vector control products. In 2013–4, seven insecticide testing facilities across sub-Saharan Africa, with technical and financial support from Innovative Vector Control Consortium (IVCC), began development and implementation of quality management system compliant with the principles of Good Laboratory Practice (GLP) to improve data quality and reliability.
Methods and principle findings
We conducted semi-structured interviews, emails, and video-call interviews with individuals at five test facilities engaged in the IVCC-supported programme and working towards or having achieved GLP. We used framework analysis to identify and describe factors affeting progress towards GLP. We found that eight factors were instrumental in progress, and that test facilities had varying levels of control over these factors. They had high control over the training programme, project planning, and senior leadership support; medium control over infrastructure development, staff structure, and procurement; and low control over funding the availability and accessibility of relevant expertise. Collaboration with IVCC and other partners was key to overcoming the challenges associated with low and medium control factors.
Conclusion
For partnership and consortia models of research capacity strengthening, test facilities can use their own internal resources to address identified high-control factors. Project plans should allow additional time for interaction with external agencies to address medium-control factors, and partners with access to expertise and funding should concentrate their efforts on supporting institutions to address low-control factors. In practice, this includes planning for financial sustainability at the outset, and acting to strengthen national and regional training capacity.
... PGT/PGS is still relatively unregulated and lacks standardization compared with other forms of diagnostic testing; however, more federal, state, and local governments are beginning to take an interest in PGT and some have begun accrediting laboratories that offer PGT (Harper et al., 2010a). [2] One step toward higher quality overall and standardization for PGT/PGS is to build consensus opinion on best practices within the PGT/PGS community, a component of the mission of the committee. The PGT consensus committee recognizes that owing to variations in local or national regulations and specific laboratory practices, there will remain differences in the ways in which PGT/PGS is practiced (from initial referral through IVF treatment, single-cell analysis to follow-up of pregnancies, births, and children). ...
... Embryos mosaic for trisomies that are associated with potential for uniparental disomy (14,15) are of lesser priority e. Embryos mosaic for trisomies that are associated with intrauterine growth retardation (chromosomes 2,7,16) are of lesser priority f. Embryos mosaic for trisomies capable of live-born viability (chromosomes 13, 18, 21) are of the lowest priority for obvious reasons. ...
Study question:
What are the good practice guidelines for Pre implantation genetic testing applicable in INDIA?
What is already known:
Pre-Implantation Genetic Testing (PGT) is not new in India. It is used to identify euploid embryos for transfer, thus enabling couples to achieve a healthy pregnancy. There has been a lot of controversy surrounding PGT in the international forums; most of these debates have failed to reach a consensus on whether PGT should be offered or its concerns be validated more.
Study design size duration:
This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on Pre implantation genetic testing and embryo biopsy practices in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics.
Participants/materials setting methods:
Expert professionals from ISAR representing clinical, embryological and genetic fields.
Main results and the role of chance:
The report is divided into various components defining the terminologies, the various requirements, qualifications, recommendations on PGT -A,M,SR, and quality management: the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow.
Limitations reasons for caution:
The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same.
Wider implications of the findings:
These guidelines can help labs across the country to standardise their PGT services and improve clinical outcomes.
Study funding/competing interests:
The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.
... 7 Cases of DNA amplification failure are mainly due to losing the biopsy samples during the tubing process, which requires repeated moving and washing. 8 Because of these losses, there may be no biopsy samples to diagnose, which is an outcome that is unacceptable for all couples. 9 Unfortunately, the conventional method relies on the manual control of micropipettes for transferring embryonic cells to PCR tubes with or without microscopic visualization. ...
... As the success of a PGT treatment cycle is the result of great attention to detail, the optimization of any procedural steps is a pragmatic goal. 8 A common characteristic between all biopsy stages is the limited quantity of samples available for genetic analysis, potentially compounded by the often sub-optimal quality of the embryo cell biopsied. 23 The cell death in TE cells, damage to genomic DNA from the laser or mechanical injury during the biopsy may also affect the quality of the biopsy samples. ...
Background:
Preimplantation genetic testing (PGT) is a powerful tool for patients with a high risk of transmitting a genetic abnormality to their children. Unlike other assisted reproductive technologies (ART), it has technical issues which remain unresolved.
Objectives:
To develop a modified tubing method for placing biopsied samples into amplification tubes for PGT.
Material and methods:
A modified tubing method was developed and applied to PGT, with the micromanipulator aiding in the fine movement of transfer pipettes, and with a microinjector to minimize the amount of medium which is transferred with the biopsy samples into the amplification tube. A total of 826 blastocysts from 222 PGT cycles performed between December 2016 and December 2019 were retrospectively analyzed. As the tubing of the cells could not always be inspected visually and they would only be detected by the presence of DNA after amplification, the main outcome measure was the amplification success rate.
Results:
The amplification success rate with the modified tubing method was 99.6%.
Conclusions:
The modified tubing method is efficient and simple. It is a promising technique for PGT tubing. To the best of our knowledge, this is the first report on the use of a modified micromanipulator and microinjector for improving the tubing rate in PGT cycles, and the presented method is by far the closest to actual use for PGT tubing.
... For instance, couples with autosomal recessive conditions, one homozygous recessive individual and one carrier, female carrier of an X-linked disorder, or an autosomal dominant condition when one parent is affected [42]. Subfertile couples, where one parent is the carrier of a chromosome translocation, mosaicism, or gonadal mosaicism, are also susceptible to this risk [44,45]. ...
A significant proportion of clinically recognized pregnancies end in miscarriage. About 50% of early pregnancy losses are due to chromosome abnormalities. In assisted reproduction technology (ART), a high proportion of top-quality embryos with morphological values are aneuploid whenever they have been evaluated in terms of genetic integrity in human preimplantation embryos either from in vitro or in vivo matured oocytes. It is plausible to think of preimplantation genetic testing (PGT) as a means of increasing pregnancy rates and minimizing the risk of fetal aneuploidy. It is believed that PGT will assume a prominent role in the field of ART, especially in a successful pregnancy, so it is embraced recently as a popular diagnostic technique. The PGT includes three sub-categories of PGT for aneuploidies (PGT-A), PGT for single gene / monogenic disorders (PGT-M), and PGT for chromosome structural rearrangements (PGT-SR). PGT-A is used to detect aneuploidies and previously it was known as PGS. PGT-M, formerly known as PGD, is intended to reduce monogenic defects. Previously known as PGS translocation, PGT-SR is PGT to identify structural chromosomal rearrangements. Since many of the old and new definitions for PGT are still vague and confusing for some researchers in the field of reproductive genetics, the main purpose of this study is to introduce all PGT classifications as well as elaborate on different aspects of this technology to improve ART outcomes.
... PGT-specific schemes are readily available for both monogenic and aneuploidy testing in Europe, and beyond. Laboratory accreditation according to ISO15189 is still considered the most effective route to quality assurance (Harper et al., 2010) and its uptake is increasing in Europe, and beyond. It needs to be noted that technique-specific guidelines, such as those for diagnostic MPS, are equally relevant and important for PGT and should be observed (Matthijs et al., 2016;Marianowski et al., 2016). ...
Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.
... PGT-specific schemes are readily available for both monogenic and aneuploidy testing in Europe, and beyond. Laboratory accreditation according to ISO15189 is still considered the most effective route to quality assurance (Harper et al., 2010) and its uptake is increasing in Europe, and beyond. It needs to be noted that technique-specific guidelines, such as those for diagnostic MPS, are equally relevant and important for PGT and should be observed (Matthijs et al., 2016;Marianowski et al., 2016). ...
Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.
... For example, extra embryos produced by cycles that are cryopreserved, presumptively for the purpose of a future pregnancy; but in many instances, they are never used by the genetic parents (Brezina and Zhao 2012). PGD is still relatively unregulated and lacks standardisation compared with other forms of diagnostic testing; however, more local governments are starting to take an interest in PGD with some even beginning to accredit laboratories that offer PGD (Harper et al. 2010). This seems to be a logical step considering the relative difficulty in achieving the highest levels of accuracy and reliability with single cells as part of PGD compare with more routine genetic testing (Harton et al. 2011). ...
Pre-implantation genetic diagnosis (PGD) became well known in Malaysia after the birth of the first Malaysian ‘designer baby’, Yau Tak in 2004. Two years later, the Malaysian Medical Council implemented the first and only regulation on the use of Pre-implantation Genetic Diagnosis in this country. The birth of Yau Tak triggered a public outcry because PGD was used for non-medical sex selection thus, raising concerns about PGD and its implications for the society. This study aims to explore participants’ perceptions of the future implications of PGD for the Malaysian society. We conducted in-depth interviews with 21 participants over a period of one year, using a semi-structured questionnaire. Findings reveal that responses varied substantially among the participants; there was a broad acceptance as well as rejection of PGD. Contentious ethical, legal and social issues of PGD were raised during the discussions, including intolerance to and discrimination against people with genetic disabilities; societal pressure and the ‘slippery slope’ of PGD were raised during the discussions. This study also highlights participants’ legal standpoint, and major issues regarding PGD in relation to the accuracy of diagnosis. At the social policy level, considerations are given to access as well as the impact of this technology on families, women and physicians. Given these different perceptions of the use of PGD, and its implications and conflicts, policies and regulations of the use of PGD have to be dealt with on a case-by-case basis while taking into consideration of the risk–benefit balance, since its application will impact the lives of so many people in the society.
... However, since April 2013 we introduced quantitative PCR (qPCR)-based trophectoderm biopsy for both monogenic diseases and chromosomal structural and/or numerical disorders diagnosis (Capalbo et al., 2015a;Treff and Scott, 2013;Treff et al., 2012). The IVF cycles requiring this analysis involve specific critical procedures that potentially expose the patients to additional hazards, whose classification, and methods for forecast and prevention have to be defined meticulously (Harper et al., 2010). This is especially important due to the fact that the EWS guarantees an electronic patient-based traceability, but it lacks an embryo-based one. ...
Preimplantation genetic diagnosis and aneuploidy testing (PGD/PGS) use is constantly growing in IVF, and embryo/biopsy traceability during the additional laboratory procedures needed is pivotal. An electronic witnessing system (EWS), which showed a significant value in decreasing mismatch occurrence and increasing detection possibilities during standard care IVF, still does not guarantee the same level of efficiency during PGD/PGS cycles. Specifically, EWS cannot follow single embryos throughout the procedure. This is however critical when an unambiguous diagnosis corresponds to each embryo. Failure Mode and Effects Analysis (FMEA) is a proactive method generally adopted to define tools ensuring safety along a procedure. Due to the implementation of a large quantitative PCR (qPCR)-based blastocyst stage PGD/PGS programme in our centre, and to evaluate the potential procedural risks, a FMEA was performed in September 2014. Forty-four failure modes were identified, among which six were given a moderate risk priority number (>15) (RPN; product of estimated occurrence, severity and detection). Specific corrective measures were then introduced and implemented, and a second evaluation performed six months later. The meticulous and careful application of such measures allowed the risks to be decreased along the whole protocol, by reducing their estimated occurrence and/or increasing detection possibilities.
... Dies hilft, einen initial rekombinan- ten Haplotyp zu identifizieren, dessen Verwendung im Rahmen einer PID mit falschen Genotypisierungsergebnissen einhergehen würde.Qualitätsmanagement: Um die Quali- tät der PID in Deutschland sicher zu stel- len, wird von den humangenetischen Einrichtungen der ernannten PID-Zen- tren eine Akkreditierung nach DIN EN ISO 15189 und eine externe Qualitätssi- cherung durch Teilnahme an geeigneten Ringversuchen (z. B. UK NEQAS und CEQAS) oder durch Organisation von Probenaustauschen der Laboratorien un- tereinander verlangt[8]. Bei der techni- schen Durchführung wird die Einhaltung der "ESHRE PGD Consortium Best Practice Guide lines" vorausgesetzt[9]. ...
Since recently, preimplantation genetic diagnosis (PGD) is allowed in Germany within narrow limits. The legal framework giving the “Präimplantationsdiagnostikgesetz” (PräimpG) and the regulation governing the preimplantation genetic diagnosis (PIDV). Meanwhile, almost all states have implemented the PIDV, ethics committees started their work and PID centers were approved. A PID can be offered to couples who, because of their genetic disposition, have a high risk for offspring with a serious hereditary disease or a serious damage to the embryo, which will lead to miscarriage or prenatal death. This requires, on the one hand, the clear identification of the disease-causing DNA alteration and, on the other hand, assisted reproductive techniques with intracytoplasmic sperm injection (ICSI). At the request of the woman or the couple, the ethics committee shall decide in each case whether a PID is permitted. In addition to the medical background, the technical methodological aspects of the cell extraction (biopsy) and of the genetic analytical methods are summarized. Ethical issues and Genetic counseling in preparation of the application to the ethics committee are also covered. Currently established ethics committees and the approved PID centers are presented. In the outlook, we discuss the importance of data collection and the newly founded working group on PGD.
... Accreditation is a laborious process to establish and even harder to maintain; however, it ensures good-quality management, which is essential in today's diagnostic laboratories. ISO 15189 is the specific international laboratory standard to which PGD diagnostic laboratories need to conform (International laboratory standard specific for medical laboratories -Medical laboratories: particular requirements for quality and competence) (Harper et al., 2010;ISO 15189, 2012). The ISO has two parts: management and technical requirements. ...
Preimplantation genetic diagnosis (PGD) aims to test the embryo for specific conditions before implantation in couples at risk of transmitting genetic abnormality to their offspring. The couple must undergo IVF procedures to generate embryos in vitro. The embryos can be biopsied at either the zygote, cleavage or blastocyst stage. Preimplantation genetic screening uses the same technology to screen for chromosome abnormalities in embryos from patients undergoing IVF procedures as a method of embryo selection. Fluorescence in-situ hybridization was originally used for chromosome analysis, but has now been replaced by array comparative genomic hybridization or next generation sequencing. For the diagnosis of single gene defects, polymerase chain reaction is used and has become highly developed; however, single nucleotide polymorphism arrays for karyomapping have recently been introduced. A partnership between IVF laboratories and diagnostic centres is required to carry out PGD and preimplantation genetic screening. Accreditation of PGD diagnostic laboratories is important. Accreditation gives IVF centres an assurance that the diagnostic tests conform to specified standards. ISO 15189 is an international laboratory standard specific for medical laboratories. A requirement for accreditation is to participate in external quality assessment schemes.
