The role of Quality Agreements in Contract Manufacturing Organizations (CMO)

The role of contract manufacturing in the pharmaceutical and life sciences industries cannot be overlooked. It has gained favor with organizations in these industries, as it allows them the luxury of outsourcing their processes relating to manufacturing or other activities to a third party, saving them costs and hassles in the short and long terms. Entrusting their processes to Contract Manufacturing Organizations (CMO’s) enables them to concentrate on their core activities such as research and new drug discovery.

With the global economy more open than it perhaps has been at any other point of time in history, and with almost no economy of any country being isolated from the forces of globalization; CMO’s are a very viable option for pharmaceutical and related companies. As long ago as 2010; the global CMO size was put at over $26 billion, with a healthy CAGR of over 10 percent. With the global pharma market having crossed a trillion dollars in 2015; there is heavy optimism for the growth of CMO in the coming years.

While these figures look encouraging; a whole lot of issues need to be considered before embarking on contract manufacturing. The most important of these is quality. Ensuring that the supplier maintains the high quality standards set out by the contracting company is a major challenge for the client company.

The Quality Agreement

Quality Agreements are a very strong tool in addressing this issue. A Quality Agreement is a contract reached between a pharmaceutical firm and a GMP Contract Manufacturer, in which the responsibilities each of these parties has towards assuring the quality, safety and efficacy of the manufactured drug, are spelt out in detailed and clear terms. This is the only real means to ensure oversight of the processes and the quality of the products. Ensuring that they comply with the GMP regulations is at the core of these requirements and expectations.

How do contracting pharmaceutical and life sciences firms draft Quality Agreements that comply with the regulatory requirements and ensure the quality of products from the supplier? What are the elements of a Quality Agreement? What due diligence and scrutiny does the contracting organization need to keep in mind when drafting a Quality Agreement?

Complete learning on all aspects of the Quality Agreement

The nitty-gritty of these elements will be taught at a webinar that is being organized by Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance. This webinar’s speaker, Roger Cowan, is the founder and owner of R Cowan Consulting Services LLC, a consulting company specializing primarily in the area of pharmaceutical contract manufacturing. The experience he has gained in the industry after having worked in it for 37 years will be in full flow at this webinar.

Please register for this webinar by visiting Contract Manufacturing Arrangements for Drugs

In-depth look at the two recent FDA and EU guidelines

Roger will explain the dynamics of a CMO Quality Agreement at this webinar. He will discuss the two recent regulatory guidelines: the EU GMP Chapter 7 “Outsourced Activities” (Revised) issued by the EU, and the Draft Guidance for Industry – “Contract Manufacturing Arrangements for Drugs: Quality Agreements”, which was issued by the FDA in May 2013. These two guidelines are important from the CMO perspective, as they offer greater depth of understanding and clarity on quality contracts.

Roger will explain what aspects of Quality Agreements need to be taken care of from a regulatory perspective. Both the FDA and the EU have laid sufficient emphasis on the control of suppliers such as CMO’s. It is expected that these new these new regulatory documents will introduce written documentation of this control. Evidence of this kind of control can be presented to FDA/EU inspectors in the form of a Quality Agreement which is specific to a particular CMO.

Writing a Quality Agreement in line with the new guidelines

The speaker will help participants gain a thorough understanding of the Quality Agreement by fully analyzing each proposed section. He will suggest how to write it keeping the new guidelines in mind. He will also detail the comparisons between the two regulatory documents and will highlight their differences. Topics of critical importance in the Quality Agreement, such as change control, documentation, facilities and equipment, lab controls, sub-contracting, etc., will be examined. He will also present an analysis of the current status of the FDA draft guidance and will review the comments that this guidance has received from the industry.

Roger will cover the following areas at this session:

o  The Who and What of a good Quality Agreement

o  What a Quality Agreement is – and is not

o  Responsibilities of the owner vs. contract facility

o  GMP responsibilities

o  A comparison of the new guidelines from the FDA and the EU.

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Who oversees the trial, has to undertake to the FDA

A vital document required when carrying out a clinical trial is FDA Form 1572 Statement of Investigator. It is a contract between the Principal Investigator (PI) and the FDA. FDA Form 1572, or just 1572, has all details of the subjects in the research, as well as the commitments the PI, who oversees the trial, has to undertake to the FDA. This commitment concerns meeting all the requirements from the FDA as they relate to the trial.

When the PI signs the FDA Form 1572, which relates to IND studies, or the “Statement of the Investigator, which is meant for IDE studies; she undertakes a commitment that she will comply with all the appropriate regulations and will be liable to facing legal action in the event of failing to do so. Hence, the FDA Form 1572 is a strongly legally binding document which sets out the terms of the commitment between the PI and the FDA.

The FDA has created the form 1572 with two main intentions:

It aids the FDA in gauging the PI’s suitability for overseeing the study, as it requires the latter to declare criteria related to this, such as experience and qualification. It also helps it understand the purpose of the study and the suitability of its methods to help it achieve its aims. Not only the FDA, but also the sponsor of the study can get this information from the form 1572.

Additionally, the FDA Form 1572, by taking an undertaking from the Principal Investigator that she will meet the requirements set out by the FDA during the trial; criminalizes the failure on the part of the PI to meet these conditions. It treats this as giving false statements, which empowers the agency to proceed legally against the PI under 18 USC 1001. When the sponsor selects the Principal Investigator to conduct a clinical trial as an investigational new drug (IND) that meets the criteria set out in 21 CFR 312.53 (c); this form has to be submitted.

Other documents accompanying the 1572

In addition, the following documents, which set out the general and specific responsibilities that the Investigators have when conducting a clinical trial; have to accompany the FDA Form 1572:

  • 21 CFR 312.50: contains the General Responsibilities of Investigators
  • 21 CFR 812.100: sets out the Responsibilities of Investigators for Biologics
  • 21 CFR 812.110: details the Responsibilities of Investigators for devices.

Get to understand the workings of FDA Form 1572

With the FDA Form 1572 being of crucial importance, compliance with it is not something that a sponsor or a PI can take lightly. Meeting the regulatory requirements set out in this document is in the interest of everyone concerned.

It is with the purpose of familiarizing the aspects relating to FDA Form 1572 that Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, is organizing a webinar.

The speaker of this webinar, Charles H. Pierce, a consultant in the Clinical Research/Drug-Device Development arena, will offer insights into the nature of the due diligence that investigators and their staff have to take in meeting their regulatory and legal responsibilities.

Please register for this highly educative webinar by visiting Form FDA 1572 Seriously

FDA Form 1572 contains nine statements, seven out of which begin with “I agree”. Some of the essential elements named in the 1572 include:

  • 21 CFR 50 (Protection of Human Subjects)
  • 21 CFR 56 (Institutional Review Boards)
  • 21 CFR 312 (Investigational New Drug Application/IND)
  • For Device studies, 21 CFR 812 (Investigational Device Exemptions/IDE) is added in place of 21 CFR 312.

Also, additional responsibilities are outlined in GCP Guidelines of E6 (4) and the Compliance Program Guidance Manual (CPGM) 7348.811. In addition to complying with the principles of Good Clinical Practices (GCP); the PI and sponsors are advised to also use their discretion.

At this session, the speaker will offer complete clarity on these aspects. The following areas will be covered at this webinar:

  • The Investigators role in the clinical research process
  • The difference between AEs and SAEs and the reporting requirements of the investigator
  • Why the investigator maintains a list of staff signatures?
  • Why the investigator files the signed and dated protocol?
  • Why the investigator is responsible for the IC process?
  • What is the legal language of the FDA Form 1572 or Device equivalent?
  • Why is Financial Disclosure information important?
  • What is the history of the drug / device regulations?

For updates from this please https://goo.gl/forms/SNAcsW8rLKPrzxLD2

The AAMI TIR 45 is invaluable in helping adapt Agile methods for medical device software

A report from the Association for the Advancement of Medical Instrumentation, namely, AAMI TIR 45, offers recommendations for how to comply with both international standards and guidance documents from the FDA when it comes to Agile practices for developing medical device software.

The AAMI TIR 45 is an attempt to align and synchronize Agile’s values, goals, principles and practices to medical device software development. It shows the ways of doing this. It seeks to remove the many misconceptions and myths surrounding the suitability and adaptability of Agile to medical device software and explains how to apply Agile methods for meeting the Quality System requirements set out for medical device software.

AAMI TIR 45 has been set out to help manufacturers of medical device software reap the benefits that Agile provides, while staying compliant with the regulatory expectations and requirements.

The AAMI TIR 45 was created because of the value that Agile can bring to medical device software. One of the reasons for which Agile was developed was to address concerns relating to the quality and efficiency present in the methods of software development that existed then. When its core features are adapted to the medical device software field, it brings enormous benefits, some of which include:

–       It allows for continuous and persistent focus on risk management, safety and delivering customer value through its method of prioritizing backlog work, and practices relating to planning and customer feedback

–       It uses continuous integration and testing to continuously and consistently assess quality

–       Through its methods of retrospective action and accountability; Agile brings in continuous improvement into the process of software development

–       By focusing on getting things done one stage at a time and thus ensuring timely and incremental completion of work and deliverables; Agile satisfies the demands and needs of the medical device company’s stakeholders in the management and quality areas.

A few reservations

Many experts in both medical device software and Agile fields have expressed reservations about the suitability that Agile has in an extremely stringently regulated area such as medical device software. They refer to the Agile Manifesto, which seems to contain value statements that seemingly contradict the values at the core of a Quality Management System.

They also draw attention to the fact that as Agile evolved at a time when there was no criticality attached to risk management and human safety; the controls needed for producing software to which safety is critical have not been embedded into Agile.

Requires proper understanding and implementation

These points notwithstanding; Agile comes with a fundamental adaptability to the context it is applied in. Implementing Agile principles and practices in a proper way makes it more than adequate in an area like medical device software, where safety is critical. It is perfectly well-suited to accomplishing the lifecycle steps prescribed in IEC 62304 and risk management under ISO 14971. It can also help achieve usability design as required under IEC 62366

A learning session on the AAMI TIR 45

Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will offer thorough clarity on the area of the suitability of the Agile to medical device software. The speaker at this session, Brian Shoemaker, will unravel the elements of AAMI TIR 45 and explain how it can be applied to medical device software smoothly and effectively in a manner that meets regulatory requirements.

Please visit Agile Meets Software Standards to register for this webinar and derive the benefit of understanding how to apply Agile principles to medical device software.

At this webinar, Brian will help understand how the AAMI TIR 45 can be the ideal roadmap for facilitating and bettering development, which benefits everyone concerned, be they development teams, companies, patients, caregivers, or regulators.

He will put this in perspective by explaining the following topics:

o  Convergence: Agile principles and regulatory needs

o  Lifecycle: incremental development, design reviews, documentation

o  Key practices: planning, collective effort, product definition

o  Implementation: evolving architecture, emergent design, continuous testing, traceability

o  Managing your software: release, configuration management, third-party software, and CAPA

Brian will cover the following areas at this webinar:

o  TIR 45 comes at a much-needed time

o  TIR 45 stitches together the important high-level concepts

o  TIR 45 outlines key practices that are needed for flexibility and quality

o  Implementation issues are not ignored

o  This TIR is actually just a starting point.

For more updates and articles AAMI TIR 45

Companies continue to increase transparency of external audit oversight

More companies are providing investors and other stakeholders with information about audit committee oversight of external auditors, according to the latest edition of the Audit Committee Transparency Barometer, an annual report released Wednesday by the Center for Audit Quality (CAQ) and Audit Analytics.

“For the fourth year in a row, audit committees have continued to enhance transparency around their oversight of the external auditor by voluntarily and broadly increasing disclosure,” Cindy Fornelli, executive director of the CAQ, said in a press release. The CAQ is affiliated with the AICPA.

The barometer found that 37% of S&P 500 companies’ proxy statements included enhanced discussions of the factors audit committees considered in recommending the appointment of the external audit firm. That’s up from 31% in 2016 and 13% in 2014.

The analysis, which also looks at mid-cap and small-call companies in the S&P Composite 1500, found that 24% of S&P MidCap 400 companies and 17% of S&P SmallCap 600 companies provided enhanced discussion of audit committee considerations in choosing an audit firm. Those percentages are up from 10% and 8%, respectively, in 2014.

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Misinterpretation of closed Data when Treated with “Normal” Statistical Methods

Geology is among the many branches of science in which compositional data (CoDa) arise naturally. In branches such as geochemistry, compositional data seem to occur typically, when one normalizes raw data or when one obtains the output from a constrained estimation procedure, such as percentages, ppm, ppb, molar concentrations, etc.

Compositional or constrained data have proved difficult to handle statistically because of the awkward constraint that the components of each vector must sum to unity. The special property of compositional data (the fact that the determinations on each specimen sum to a constant) means that the variables involved in the study occur in constrained space defined by the simplex, a restricted part of real space.

It is important for geochemists and geologists in general to be aware of the fact that the usual multivariate statistical techniques are not applicable to compositional data. They need to have access to appropriate techniques as they emerge and become available.

Pearson was the first to point out dangers that may befall the analyst who attempts to interpret correlations between Ratios whose numerators and denominators contain common parts. More recently, Aitchison, Pawlowsky-Glahn, S. Thio, and other statisticians have developed the concept of Compositional Data Analysis, pointing out the dangers of misinterpretation of closed data when treated with “normal” statistical methods.

Learning about all elements of CoDa

A webinar from Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will throw light on all the important aspects of CoDa. At this session, Ricardo Valls, a professional geologist with thirty years in the mining industry, and who has extensive geological, geochemical, and mining experience, managerial skills, and a solid background in research techniques; will be the speaker.

To gain insights into CoDa, please enroll for this webinar by visiting  real case studies developedreal case studies developed

At this session, Ricardo will present several real case studies he has developed, to demonstrate the advantages of applying various aspects of the CoDa analysis in the search for and evaluation of ore bodies by comparing them with regular statistical modelling of geochemical data.

At this webinar, which will be of high value to personnel involved in mining, such as Geologists, Geochemists, Exploration Personnel, Graduate Students, and Post-Graduate Students; Ricardo will cover the following areas:

o  History of the Problem

o  The Current Situation

o  The Model

o  Normal Statistical Processing of the Data

o  Compositional Data Analysis

o  Factor and Principal Component Analysis

o  Dealing with zero and b.d.l. Values

Conclusions and Recommendations.

For more click the advantages of applying different aspects

Centrelink delays leave recipients unable to pay for rent or food

Problems with Centrelink payments caused “extremely stressful” delays for some of Australia’s most disadvantaged groups this week, while newly released figures show complaints about the agency jumped by more than 50,000 in the last financial year alone.

The delays to scheduled payments on Monday appear to have affected Newstart recipients. One welfare recipient told Guardian Australia the delay left him with $2 to his name and unable to afford food. He said he was saved only by the generosity of a friend who bought his groceries.

“I wasn’t sure when it was going to get resolved, [or] if it was even going to get resolved,” the Newstart recipient said, speaking on condition of anonymity. “I didn’t know how I was going to pay rent, or for food.”

The Department of Human Services confirmed short delays in the making of payments but did not answer questions on how many people or what payment types were affected.

The department issued a brief statement saying that it had worked with the Reserve Bank of Australia to ensure the “timely release of a small number of payments which were slightly delayed on Monday”.

“All financial institutions processed payments yesterday apart from one, which finalised payments this morning,” department spokesman Hank Jongen said. “The department has well established arrangements with financial institutions to conduct processing when payment files delivered via the Reserve Bank occur on the same day they are due to be made.”

Confused welfare recipients voiced their anger on social media or visited local Centrelink offices.

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Learn How to manage and improve Human reliability

Manufacturing is a behemoth of an activity that straddles several industries. Modern manufacturing has come a long way from the days of its infancy, which can be traced to the Industrial Revolution of some 250 years ago. Getting advanced and refined at many stages; production or industrialization or manufacturing is the lifeblood of most of the world’s economies. Automation in the processes may have been introduced in many industries; yet, manufacturing continues to depend heavily on human labor.

Although industrialization and manufacturing came about from the human intellect and endeavor; it is still prone to human error. It is a fact that wherever there is human involvement, there is scope for error. This is because we are humans after all. We can take the highest diligence in the work we do, but can make errors. On most occasions, these are unintended, but the result is negative. Errors in the manufacturing processes will continue so long as humans are involved in manufacturing to some or another degree.

Human errors can bring high costs

Manufacturing being an interlinked activity; human errors can cause many problems. One small error in the chain can affect the whole process, triggering a whole chain of errors. Although precise assessments cannot be made of the loss caused by human error; it is roughly estimated that the American and British pharma industries alone accrue losses of around $25 billion a year due to this factor.  Further, unexpected runtime error, which results in loss of more than a third of the productive time; is a direct consequence of human error. Human error can also lead to losses relating to quality and production. It is the cause of many performance issues.

It has to be understood that even with the knowledge of the consequences of human error, and with all the advancements and developments that have been made in high end, precise technologies and processes; the manufacturing sector is not likely to eliminate human errors. They can only be mitigated and minimized.

Getting to the root of the problem is important

Most manufacturers resort to a disjointed approach to human error. The positive approach to containing human error should be to locate its source. It is a fact that human error starts at the earliest stage, the design stage. Although this is known to many manufacturers and they are equally aware of the fact that training is a great tool to reduce human error; many in the manufacturing sector don’t take training seriously.

Along with training, other factors such as controlling the procedures and the workplace environment, where the various variables that affect human behavior converge, need to be taken into consideration. The manufacturer should directly address the systemic weaknesses to improve or fix them. An understanding of human behavior and the psychology of error is necessary to do this. Getting to the root of human error involves these among others:

 

o  Implementing human factors in manufacturing

o  Communicating in the right manner

o  Fostering continuous practice

o  Imparting the proper methods of training

o  Offering a thorough description of the right procedures with the right instructions

o  Bringing about a positive work environment

o  Putting the right processes in place.

A training session on understanding human error

Ginette Collazo, a human error and human behavior expert who has spent more than 15 years in technical training, organizational development and human reliability areas, will be the speaker at a webinar on human error that Compliance4All, a highly acclaimed provider of professional trainings for all the areas of regulatory compliance, is organizing.

Please enroll for this webinar by visiting Human Error Reduction

Practical approaches to all areas of human error

Ginette will offer a complete understanding of the nature of human error, its roots, and its psychology. This webinar seeks to help regulatory and quality professionals get a thorough idea of the factors that cause human error. In order to facilitate proper understanding of this topic, the speaker will offer practical approaches and tools to address human performance issues in manufacturing. The understanding of the human psychology and behavior behind human errors that she will offer will give insights to where the weaknesses lie. This in turn will help to address the human performance issues and help correct and prevent recurrences of human error.

The following areas will be covered at this webinar:

  • Background on Human Error Phenomena and measurement
  • Importance of Human Error Prevention/reduction
  • Quantitative and qualitative information gathering
  • Why do we need tools for human error reduction programs?
  • Training as a tool and human error
  • Facts about human error and training
  • Human Error as the Root Cause: what to do and how to measure it
  • Tools
  • Prediction
  • Root Cause Analysis
  • Cognitive load assessment
  • Systems available
  • Human error rate
  • Floor checklist
  • Interview questions
  • Human error rates and other metrics
  • Trending and tracking
  • CAPA effectiveness
  • Metrics and Human Error
  • KPI’s
  • Human Error rate
  • 1st time pass rate
  • Overall equipment effectiveness (OEE)
  • Trending /Tracking

For updates click the below Link Human error rates and other metrics