Vertex Pharmaceuticals: European Recommendation For Kalydeco Additional Mutations

Orphan Druganaut Blog

On June 27th, Vertex Pharmaceuticals gets European CHMP’s (Committee for Medicinal Products for Human Use) positive opinion recommending the approval of orphan drug Kalydeco (Ivacaftor) for Cystic Fibrosis (CF) patients, ages 6 and older, who have 1 of the following 8 non-G551D gating mutations, in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene:

•G178R   •S549N    •S549R   •G551S   •G1244E    •S1251N   •S1255P   •G1349D.

These 8 additional mutations affects approximately 250 patients in Europe. The next step, is for the European Commission (EC), that has the authority to approve drugs for the European Union, to review the CHMP’s positive opinion. The EC usually follows the recommendation of the CHMP and issues a marketing approval within 3 – 4 months. Kalydeco receives approval in Europe in July 2012 for patients with CF ages 6 and older, who have at least 1 copy of the G551D mutation, which is the most common gating…

View original post 277 more words




ニューサイエンス マグネシウム

ニューサイエンス マグネシウムは吸収性や安全性を考慮した特製酵母ミネラルで、鉱物マグネシウムと違い、キレート状態の有機マグネシウムを無添加でGMP取得工場にて植物性カプセルに凝縮した高品質マグネシウムサプリメントです。



ニューサイエンス マグネシウムの特徴

ニューサイエンス マグネシウムは一般的な合成由来のマグネシウムサプリや鉱物マグネシウムと違い安全や吸収に優れた特製酵母ミネラルの体にとって自然なキレート有機マグネシウムです。香料や着色料、保存料など合成添加物は無添加で製造も*GMP取得工場、高品質だから安心です。

*GMPとはGood Manufacturing Practiceの略で品質管理を行っている工場で製造されたことを表しています。


ニューサイエンス マグネシウムについて

ニューサイエンス マグネシウム公式ページ


ニューサイエンス マグネシウム正規販売店ページ

ニューサイエンス マグネシウム正規販売楽天店ページ


ニューサイエンス サプリメント

View original post

Surviving an audit, in simple terms

Dycem CleanZone Technology

ARTICLE REFERENCE: How to survive an FDA audit by Paul Dupontaudit_image_cleanroomThe arrival of an audit inspection can instill feelings of fear and anxiety that can be duly diffused with the right preparation and mentality.

We’ve compiled a few concise pointers to help see you through the process.

Keep your employees in the loop

Identify several key members of personnel to liaise with the investigator during the audit process, and make them aware of their role. Prepare them as best as possible, so that they are in line with your organisation’s approach to the audit.


Do your research

Spend some time to familiarise yourself with the regulations, to make sure that your daily processes conform to the required standard.

Keep an open mind

Try not to be overly defensive in response to the investigator’s criticisms. Think clearly, and discuss the issue at hand openly. ‘You’re more likely to respond to…

View original post 127 more words

What GMP Changes can we still expect for 2014?

New Drug Approvals

What GMP Changes can we still expect for 2014?

Heraclitus once said: “There is nothing permanent except change”. This statement is even true for the rather conservative GMP environment. What can we still expect for 2014? The answer to that question can be found in a work plan of EMA’s GMP/GDP Inspectors Working Group.

What are the coming plans?

View original post 155 more words

Stability Data for ANDAs in the USA: a new Q&A Document of the FDA provides further Clarity

New Drug Approvals

Stability Data for ANDAs in the USA: a new Q&A Document of the FDA provides further Clarity
The applicant for an ANDA in the USA has to submit data of several stability tests. The FDA guidance on this topic coming into force last year left open some issues, however, that now are clarified with a questions and answers document published lately.

Read more.,8489_n.html

Stability Data for ANDAs in the USA: a new Q&A Document of the FDA provides further Clarity

The FDA Guidance for Industry with the title “ANDAs: Stability Testing of Drug Substances and Drug Products” was published in the Federal Register on 20 June 2013 (also see our News dated 1 August 2013) and is addressed to applicants for ANDAs in the USA. This guidance describes the stability data the FDA expects in the documents submitted for an ANDA and is rather short having…

View original post 1,031 more words

The US FDA has issued a Warning Letter to Tianjin Zhongan Pharmaceutical Co. Ltd. in Tianjin, China.

New Drug Approvals

FDA issues Warning Letter for API Facility,S-WKS_n.html
The US FDA has issued a Warning Letter to Tianjin Zhongan Pharmaceutical Co. Ltd. in Tianjin, China. The company produces APIs and failed to establish adequate GMP procedures at the facility. Read more about the FDA Warning Letter.

FDA issues Warning Letter for API Facility
The US FDA has issued a Warning Letter to Tianjin Zhongan Pharmaceutical Co. Ltd. in Tianjin, China. The company produces APIs and failed to establish adequate GMP procedures at the facility.

For quite some time India was in the center of attention and very little was heard about GMP problems in China (see also RAPS article). This is a bit surprising because a number of non-compliant facilities have been detected in the past. Also the facilities which caused the Heparin Scandal were located in China. The last enforcement action from FDA which became public referred to Import…

View original post 432 more words

The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes

New Drug Approvals

somatostatin receptor antagonist

C27 H23 F N8 O



1H-Pyrido[3,4-b]indole, 3-[5-(4-fluorophenyl)-1H-imidazol-2-yl]-2,3,4,9-tetrahydro-1-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(1-methyl-1H-pyrazol-4-yl)-, (1R,3R)-


Merck & Co. (Originator)

Somatostatin srif1C (sst3) Antagonists

The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes 
(ACS Medicinal Chemistry Letters) Thursday May 10th 2012
Author(s): Shuwen HeZhixiong YeQuang TruongShrenik ShahWu DuLiangqin GuoPeter H. DobbelaarZhong LaiJian Liu,Tianying JianHongbo QiRaman K. BakshiQingmei HongJames DellureficioAlexander PasternakZhe FengReynalda deJesusLihu YangMikhail ReibarkhScott A. BradleyMark A. HolmesRichard G. BallRebecca T. RuckMark A. Huffman,Frederick WongKoppara SamuelVijay B. ReddyStan…

View original post 1,766 more words

New e-book: Case Studies in Sample Storage

New Drug Approvals

New e-book: Case Studies in Sample Storage

Learn how lab professionals solved their sample storage problems at leading research organizations. Case studies include adapting sample storage for changing demands in compound management and incorporating sample libraries from acquired companies.


View original post

The Seven Basic Tools of Quality



The Seven Basic Tools of Quality


These are the “must” list for SPC programs. Anyone installing and using an SPC program will use most of these seven tools.


1. Flowcharts– A pictorial (graphical) representation of the process flow – showing the process inputs, activities, and outputs in the order in which they occur.


2. Checksheets – A list of items inspected (checked). The list is usually organized in a standardized format designed to facilitate information gathering and, later, quantitative analysis. It also assures that different people will collect required information in the same way.


3. Histograms – A graphical summary of variation in a set of data. A pictorial means of organizing, summarizing, analyzing, and displaying data.


4. ParetoAnalysis – Uses a specially organized histogram (the Pareto chart) to provide a picture that instantly identifies those problem of greatest concern – those problems that should be addressed first.


5. Cause and effect diagram – As the name implies, this tool is just a tool of causes and effects diagrammed to show the interrelationships. The diagram is a form of tree diagram on its side so that it looks like a fishbone. It is also called Ishikawa diagram after the man who invented it.


6. Scatter diagram – Cartesian coordinate type (X,Y graphs) that illustrate cause and effect relationships between two types of data.


7. Control Charts – Graphs of one or more important characteristics of a product. They are statistical techniques to analyze the process, and to provide information for correction and improvement of the process, and thus the products produced on that process.

Seven new quality tools


1. Affinity diagrams – The affinity diagram is a visual tool that allows an individual or a team to group a large number of ideas, issues, observations or items into categories for further analysis. The tool groups the ideas in a way that allows those with natural relationships or relevance to be placed together in the same group or category.


2. Arrow Diagrams – The arrow diagram—also known as activity diagram, network diagram, activity chart, node diagram or critical path method chart—is used to illustrate the order of activities of a process or project. Makes use of program evaluation review technique (PERT) and the critical path method (CPM)


3. Matrix diagram – Analysis relations between two different factors. Also used in developing customer requirements into design requirements, then into vendor or purchasing requirements, and then into production requirements (In this form it is also called as Quality Function Deployment – QFD – Diagram)


4. Matrix Data analysis diagram – Applies quantitative analysis to the matrix diagram.


5. Process decision program chart (PDPC) – Used to guide the implementation process. It organizes each possible chain of events in a complex plan so that all possible events are identified and planned.  For instance, anything that can possibly can go wrong will be identified, and a plan, and resources, already formulated in case any of these problem occur.


6. Relations Diagram – (Also called the interrelationship diagram). Analyses the interrelationships of complex systems, i.e., which portions of the system relate to which other portions, and how and to what extent.


7. Tree Diagram – A tree diagram allows you to detail a conceptual or high level goal into more operational tasks to achieve the desired result. The tree diagram starts with one item that branch into two or more branches, each of which branches into two or more, and so on.


Reference used : Book ” Statistical Process Control” By Leonard A. Doty

ASQ Quality Progress Magazine April 2012 edition



The Seven Basic Tools of Quality is a designation given to a fixed set of graphical techniques identified as being most helpful in troubleshooting issues related to quality.[1] They are called basic because they are suitable for people with little formal training in statistics and because they can be used to solve the vast majority of quality-related issues.[2]

The seven tools are:[3][4][5]

The designation arose in postwar Japan, inspired by the seven famous weapons of Benkei.[6] It was possibly introduced by Kaoru Ishikawa who in turn was influenced by a series of lectures W. Edwards Deming had given to Japanese engineers and scientists in 1950.[7] At that time, companies that had set about training their workforces in statistical quality control found that the complexity of the subject intimidated the vast majority of their workers and scaled back training to focus primarily on simpler methods which suffice for most quality-related issues.[8]

The Seven Basic Tools stand in contrast to more advanced statistical methods such as survey sampling, acceptance sampling, statistical hypothesis testing, design of experiments, multivariate analysis, and various methods developed in the field of operations research.[9]

The Project Management Institute references the Seven Basic Tools in A Guide to the Project Management Body of Knowledge as an example of a set of general tools useful for planning or controlling project quality.[10]


See also


  1. Montgomery, Douglas (2005). Introduction to Statistical Quality Control. Hoboken, New Jersey: John Wiley & Sons, Inc. p. 148. ISBN 978-0-471-65631-9. OCLC 56729567.
  2. Ishikawa, Kaoru (1985), What Is Total Quality Control? The Japanese Way (1 ed.), Englewood Cliffs, New Jersey: Prentice-Hall, p. 198, ISBN 978-0-13-952433-2, OCLC 11467749, “From my past experience as much as ninetey-five percent of all problems within a company can be solved by means of these tools.”
  3. Nancy R. Tague (2004). “Seven Basic Quality Tools”. The Quality Toolbox. Milwaukee, Wisconsin: American Society for Quality. p. 15. Retrieved 2010-02-05.
  4. Ishikawa, Kaoru (1985), What Is Total Quality Control? The Japanese Way (1 ed.), Englewood Cliffs, New Jersey: Prentice-Hall, p. 198, ISBN 978-0-13-952433-2, OCLC 11467749, “Elementary Statistical Method (the so-called Seven Tools) 1. Pareto chart: The principle of vital few; trivial many 2. Cause and effect diagram (This is not precisely a statistical technique) 3. Stratification 4. Check sheet 5. Histogram. 6. Scatter diagram (analysis of correlation through determination of median; in some instances, use of binomial probability paper) 7. Graph and control chart (Shewhart control chart)”
  5. Imai, Masaaki (1986), Kaizen (Ky’zen), the Key to Japan’s Competitive Success (1 ed.), New York: Random House, pp. 239–240, ISBN 9780394551869, OCLC 13010323, “The seven statistical tools used for such analytical problem-solving are: 1. Pareto diagrams […] 2. Cause-and-effect diagrams […] 3. Histograms […] 4. Control charts […] 5. Scatter diagrams […] 6. Graphs […] 7. Checksheets.”
  6. Ishikawa, Kaoru (1990), Introduction to Quality Control (1 ed.), Tokyo: 3A Corp, p. 98, ISBN 978-4-906224-61-6, OCLC 23372992, “They were named the Seven QC Tools after the famous seven weapons of the Japanese Kamakura-era warrior-priest Benkei which enabled Benkei to triumph in battle; so too, the Seven QC Tools, if used skillfully, will enable 95% of workplace problems to be solved. In other words, intermediate and advanced statistical tools are needed in about only 5% of cases.”
  7. “The seven basic tools of quality”. London: Improvement and 2007-11-30. Retrieved 2013-05-18. “Ishikawa had a desire to ‘democratise quality’: that is to say, he wanted to make quality control comprehensible to all workers, and inspired by Deming’s lectures, he formalised the Seven Basic Tools of Quality Control.”
  8. Ishikawa, Kaoru (1985), What Is Total Quality Control? The Japanese Way (1 ed.), Englewood Cliffs, New Jersey: Prentice-Hall, p. 18, ISBN 978-0-13-952433-2, OCLC 11467749, “It is true that statistical methods are effective, but we overemphasized their importance. As a result, people either feared or disliked quality control as something very difficult. We overeducated people by giving them sophisticated methods where, at that stage, simple methods would have sufficed.”
  9. Ishikawa, Kaoru (1985), What Is Total Quality Control? The Japanese Way (1 ed.), Englewood Cliffs, New Jersey: Prentice-Hall, pp. 198–9, ISBN 978-0-13-952433-2, OCLC 11467749, “I divide statistical methods into the following three categories according to their level of difficulty. 1. Elementary Statistical Method (the so-called Seven Tools) […] 2. Intermediate Statistical Method […] 3. Advanced Statistical Method (using computers concurrently)”
  10. A Guide to the Project Management Body of Knowledge. Newtown Square, PA: Project Management Institute. 2013. pp. 236–238. ISBN 978-1-935589-67-9.






The purpose of a flowchart is to provide a graphic representation of the elements, components, or tasks associated with a process.



Flowcharts are helpful for documentation purposes and, through standardized symbols, promote a common understanding of process steps and the relationships/ dependencies among those process steps.


Flowcharts can be prepared for and used at a high level, where readers/users of the flowcharts may not be familiar with process-specific jargon or terminology. In the high-level application, flowcharts are intended to help readers/users understand what may be a complex process without providing unnecessary, and potentially confusing, detail.


Likewise, flowcharts can be prepared for and used at a detail level where readers/users have familiarity and expertise with a given process. In the detail-level application, flowcharts are intended to help readers/users perform analyses most commonly related to optimization or process improvement.



  1. Select a start and stop point. A flowchart, by definition, must specify start and end points. Since it is possible to have many flowcharts describing various sections, elements, or components of a process, particularly when the process gets large and complex, start and end points for flowcharts are defined in terms of boundaries. Boundaries are naturally occurring breaks or division points that separate processes or systems at the macro level or sections, elements, or components of a process at the micro level.


  1. List major steps/tasks and decision points. List, in sequential order, each of the major steps or tasks and decision points that occur as part of the process between the start and stop points.


  1. Use standardized graphical symbols to document the process. Using standardized symbols, document each of the steps/tasks identified above. Placement of appropriately labeled symbols and use of arrows defines the sequence of events. Four primary flowcharting symbols are depicted in Figure. While there are many symbols for flowcharting, these primary flowcharting symbols are capable of an adequate for documenting any process.


  1. Review results. Compare the flowchart with the process to verify that the flowchart is complete and accurately describes the process. Having more than one person independently verify the flowchart is generally considered standard protocol.




Hallock, Alper, and Karsh (2006) present a process improvement study on diagnostic testing in an outpatient healthcare facility. The purpose of the study was to determine what factors contributed to the delay of notification of test results to patients. A general flowchart for overall diagnostic testing process was presented similar to the one in Figure.






Different Storage Conditions and Stability Characteristics for Generics and Innovator Product: Is that allowed?

Different Storage Conditions and Stability Characteristics for Generics and Innovator Product: Is that allowed?

It may happen – in the development of generic medicinal products – that the in-use stability properties or the storage conditions deviate from those of the innovator product. The question whether this is basically allowed or only allowed with restrictions in the context of the application for authorisation of a generic product has been answered by the EMA and put on its updated Q&As webpage. The answer to the following two questions was published as supplement to the Q&As:

  • “Is it allowed that the in-use stability of one product deviates from other authorised products (e.g. regarding storage time, storage conditions)?
  • Is it allowed that the storage condition of one product deviates from other authorised products (e.g. storage in refrigerator versus storage at temperatures not exceeding 25°C)?”

The EMA clearly states in the answer to both questions “each product will be assessed on its own merits”. At the same time, the EMA takes into consideration whether differences in in-use stability and/or storage conditions potentially could lead to detrimental medication errors (wrong dosing). In such a case, the EMA cannot accept the differences and will delay the treatment of the application until the problem has been solved. In its answer, the EMA refers to a position paper of the CHMP which discusses medication errors caused by differences between generics and innovator products. This position paper is dated 30 May 2013 and its title is “Position paper on potential medication errors in the context of benefit-risk balance and risk minimisation measures“. The different in-use stability and storage conditions aren’t explicitly addressed in the document. That’s the reason why the EMA felt compelled to clarify those questions in the Q&As.