A Systematic Approach to Implementing Statistical Methodologies

Focusing exclusively on qualification efforts without understanding the manufacturing process and associated variations may not lead to adequate assurance of quality.

In Guidance for Industry Process Validation: General Principle and Practices, process validation is defined as, “”…the collection and evaluation of data, from the process design stage through commercial production..” The guidance further delineates the ‘process design stage through commercial production’ into three distinct stages of the product lifecycle:

Stage 1: Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.

Stage 2: Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

Stage 3: Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

The first stage of process validation is process design. The Process Validation guidance document states, “A successful validation program depends on information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control of a manufacturing process that results in products with desired quality attributes:

Manufactures should:

  • Understand the sources of variation
  • Detect the presence and degree of variation
  • Understand the impact of variation on the process and ultimately on product attributes
  • Control the variation in a manner commensurate with the risk it represents to the process and product.”

The second stage of process validation is process qualification. Although stage 2 has two elements, this course will focus on recommendations for the second element, PPQ. PPQ “combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches.” Additionally, the process validation guidance document that “Each manufacturer should judge whether it has gained sufficient understanding to provide a high degree of assurance in its manufacturing process to justify commercial distribution of the product. Focusing exclusively on qualification efforts without understanding the manufacturing process and associated variations may not lead to adequate assurance of quality.”

The third stage of process validation is continued process verification. The process validation guidance document defines the need for this stage: “After establishing and confirming the process, manufacturers must maintain the process in a state of control over the life of the process, even as materials, equipment, production environment, personnel, and manufacturing procedures change.” Manufacturers should use ongoing programs to collect and analyze product and process data to evaluate the state of control of the process. These programs may identify process or product problems or opportunities for process improvements that can be evaluated and implemented through some of the activities described in Stages 1 and 2.”

This course focuses on how to establish a systematic approach to implementing statistical methodologies into a process validation program consistent with the FDA guidance. It begins with a primer on statistics, focusing on methods that will be applied in each remaining chapter. Next, it teaches the application of statistics for setting specifications and assessing measurement systems (assays), two foundational requirements for process validation. Lastly, the course applies statistic through the three stages of process validation defined by requirements in the process validation regulatory guidance documents. Methods taught through all three stages are recommended by regulatory guidance documents; references to the specific citations in the guidance documents are provided.

Areas covered by the Instructor:

  • Apply statistics to set specifications and validate measurement systems (assays)
  • Develop appropriate sample plans based on confidence and power
  • Implement suitable statistical methods into a process validation program for each of the three stages
  • Stage 1, Process Design: utilize risk management tools to identify and prioritize potential critical process parameters; and define critical process parameters and operating spaces for the commercial manufacturing process using design of experiments (DOE)
  • Stage 2, Process Qualification: assess scale effects while incorporating large (pilot and/or commercial) scale data; develop process performance qualification (PPQ) acceptance criteria by characterizing intra and inter-batch variability using process design data and batch homogeneity studies; and develop an appropriate sampling plan for PPQ
  • Stage 3, Continued Process Verification: develop a control plan as part of a risk management strategy; collect and analyze product and process data; and ensure your process is in (statistical) control and capable.

Who will benefit by this:

  • Process Scientist/Engineer
  • Design Engineer
  • Product Development Engineer
  • Regulatory/Compliance Professional
  • Design Controls Engineer
  • Six Sigma Green Belt
  • Six Sigma Black Belt
  • Continuous Improvement Manager

Click and register for 2 day seminar

Seminar on Validation and Troubleshooting of Pharmaceutical Water Systems

 Description:

This course is designed to provide a microbiology-focused education about all aspects of water systems and how biofilm manages to thrive there. Prior microbiological education or training, though a plus, is not a requirement because engineers and other non-biologists also need this training if they are involved with any aspect of water systems. The instructor will provide the necessary background needed to understand this very important subject matter. This understanding is essential to the proper design, validation, operation, monitoring, maintenance, troubleshooting, and excursion investigations of a high purity water system. Without this understanding, water system control consists of a set of rules that often don’t work and can cause very costly system downtime or even product recalls, and leaves the user without a clue as to what went wrong or how to effectively fix it so it doesn’t recur.

Why you Should attend:

Much fear and hype exists with pharmaceutical biofilms, especially those in water systems. Long term biofilm control cannot be achieved from a blind set of hand-me-down rules for design and operation. One must truly understand biofilm to be able to control it. And because every water system is unique, understanding how biofilm is trying to grow in your system, which could be different than any other system. This course will give you that understanding that is translatable to any system, so that uneventful microbial control is possible. Without this understanding you will quickly find that blind rules for operation (and design) eventually fail to work, and the consequences of failure will far exceed the educational costs that could have prevented it.

Who Will Benefit:

This 2-day course is particularly relevant to managers, supervisors, and operatives taking on new responsibilities related to water, but also for experienced water personnel to learn the “true” whys behind what they do and perhaps better ways of doing things. Specific positions that would benefit are:

  • Microbiology Laboratory supervisors and analysts responsible for water sampling and testing
  • Quality Assurance personnel responsible for water system deviation management and change control
  • Regulatory and Compliance professionals responsible for FDA interactions
  • Process and Utility Engineers responsible for water system maintenance, repairs, troubleshooting, and excursion mitigation
  • Facility Engineers responsible for water system design or renovation

Agenda:

Day 1 Schedule

Lecture 1:

What Makes Water Systems Have Microbial Quality Problems

  • Understand biofilm basics and how it develops
  • Understand the impact of biofilm on the commonly used purification unit operations
  • Understand how various commonly used microbial control strategies work (or don’t work) to control biofilm development
  • Understand the how, where, and why of microbial monitoring, action levels, etc.
  • Debunk a few water system myths
  • Get answers to your own water system questions

Lecture 2:

Successful Sanitization Approaches for Trouble-Free Water Quality

  • Material and construction limitations
  • Continuous vs intermittent sanitization
  • The importance of biofilm removal
  • How sanitants work (or don’t work)
  • When to sanitize
  • Troubleshooting sanitization problems

Lecture 3:

Water System Validation by Logic Instead of Tradition

  • Why validate a water system?
  • Basic ground rules for water systems before you validate them
  • Micro Test Method “validation”
  • Minimum validation expectations
  • How to figure out what you should validate
  • What happens after the honeymoon is over
  • Is validation ever really over?
  • Special considerations for lab water systems
  • Are packaged waters a viable option?

Lecture 4:

Implementing Changes to a Validated System

  • Purpose of a Change Control program – a help, not a hindrance
  • When is a change major vs minor, requiring full vs limited re-qualification?
  • What about water use during re-qualifications?
  • FDA validation expectations
  • Reliance on logic and common sense and the disservice of precedent and paradigms
  • Additional useful tips

Lecture 5:

Reducing Water Microbial Excursions & Improving Investigations

  • What are excursions?
  • Water system dilemma: process control or quality control (utility or raw material), or both
  • Intended roles of Alert/Action Levels and Specifications
  • Investigation, necessary and often fruitless
  • Excursion responses and impact
  • Criticality of valves, hoses, & outlet flushing
  • Diagnosing the source of the problem
  • Minimizing unnecessary excursion responses through best practices

Day 2 Schedule

Lecture 6:

Understanding and Controlling Endotoxin

  • Where does endotoxin come from?
  • What are the properties of endotoxin?
  • How do you get rid of it?
  • How do you detect it?
  • What assay controls are used?
  • What are the endotoxin specs for water?
  • How do you control it?

Lecture 7:

Harmonizing vs Optimizing Water Microbial Testing for System Quality Control

  • Water harmonization that has occurred
  • Water Micro TM “Dis-Harmonization”
  • A little about Biofilm
  • Biofilm diversity in water systems
  • Micro TM options and evaluation protocol
  • The good and bad of Micro harmonization
  • Where RMMs can fit in
  • Parting wisdom

Lecture 8:

Microbial Enumeration Issues with High Purity Water Systems

  • Microbial Enumeration Issues with High Purity Water Systems
  • Biofilm enumeration issues (planktonic vs surface)
  • Traditional cultivative approach issues
  • Validation of your test method
  • Alternative TM choices (advantages/disadvantages)
  • Significance of water isolates
  • Sampling issues
  • Establishing Alert/Action Levels and Water Specs and defending them to FDA

Lecture 9:

Water System Investigation “How-To’s” and Example Case Studies

  • Gathering and assessing existing data and symptoms
  • Considering user opinions
  • Investigation approach elements
  • Recognizing red herrings/false positives
  • Recognizing possible root causes
  • Water system contamination case studies
  • Parting kernels of water system wisdom

Lecture 10:

What USP Does and Doesn’t Say about PW, WFI, Pure Steam and Micro Issues

  • PW, WFI, Pure Steam micro specifications?
  • <1231> Starting water issues
  • <1231> Misunderstood issues clarified
  • <1231> Microbiological test issues clarified
  • <1231> Suggested micro test method
  • <1231> Micro Specifications
  • <1231> Alert and Action Levels and max’s
  • Recent/Upcoming USP water changes
  • Discrepancies between pharmacopeia’s

 

Speaker:

Dr Teri C. Soli

Principal Consultant, Soli Pharma Solutions

T.C. Soli is a Ph.D. Microbiologist and President of Soli Pharma Solutions, Inc. offering troubleshooting and training expertise covering water systems, sterilization, sterile and non-sterile manufacturing, microbiological laboratories, and microbial and beta-lactam contamination control. He has 38 years of pharmaceutical experience as a consultant and with operating companies including DSM Pharmaceuticals, Glaxo Wellcome, Burroughs Wellcome, and Pfizer.

His career-long water systems and contamination troubleshooting experience, coupled with water-related USP, ISPE, PhRMA, and PDA committee involvements, afford him practical knowledge about contamination control; cleaning, sterilization and process validation; and all aspects of high purity water systems.

Location:  Philadelphia, PA Date: April 23rd & 24th, 2019 and Time: 9:00 AM to 6:00 PM

Venue:  DoubleTree by Hilton Philadelphia Airport, 4509 Island Avenue, Philadelphia, PA 19153

 

 

Price:

1 ATTENDEE $2,000, Register for 1 attendee

5 ATTENDEES $10,000, Register for 5 attendees

10 ATTENDEES $20,000, Register for 10 attendees

Until March 20, Early Bird Price: $2,000.00, From March 21 to April 21, Regular Price: $2,200.00

 

Sponsorship Program benefits for seminar

For More Information– 

 

Contact us today!

NetZealous LLC DBA GlobalCompliancePanel

globalcompliancepanel@gmail.com

Toll free: +1-800-447-9407

Phone: +1-510-584-9661

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Thousands of drugs at risk if no Brexit deal, European pharmaceutical companies warn

Brexit threatens the free flow of these goods, given stringent medicine regulations that may require the retesting of drugs shipped across borders in the absence of an agreed trading arrangement.

Thousands of d.jpg

Supplies of thousands of medicines are at risk of disruption if Britain leaves the European Union without a trade deal, European pharmaceutical companies warned on Thursday. More than 2,600 drugs have some stage of manufacture in Britain and 45 million patient packs are supplied from the UK to other European countries each month, while another 37 million flow in the opposite direction. Brexit threatens the free flow of these goods, given stringent medicine regulations that may require the retesting of drugs shipped across borders in the absence of an agreed trading arrangement.

The European Federation of Pharmaceutical Industries and Associations (Efpia) said a survey of its members showed 45 percent of companies expected trade delays if Britain and Europe fell back onto World Trade Organization rules after Brexit. Drugmakers also face an additional hurdle when it comes to licensing their products, since more than 12,000 medicines will require a separate UK licence in order for them to be prescribed. “For life-saving and life-improving medicines, the EU and UK cannot afford to wait any longer to ensure that the necessary cooperation on medicines is in place from the day the UK leaves the EU,” said Efpia Director General Nathalie Moll.

Pharmaceutical companies have insisted since last year’s Brexit referendum that a comprehensive agreement is needed to ensure maximum alignment between EU and British pharmaceutical regulations. But with the clock ticking down to Brexit in March 2019 with no sign yet that a trade deal will be concluded, many companies are now starting to draw up plans to protect drug supply chains, including building extra testing centres in Europe.

 

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Lonza news Tolvaptan identified as a treatment for autosomal dominant polycystic kidney disease

A phase 3 trial studying the effects of tolvaptan has found that the drug slowed the rate of decline in kidney function in patients with polycystic kidney disease…

Tolvaptan identified

A phase 3 trial studying the effects of tolvaptan has found that the drug slowed the rate of decline in kidney function in patients with the most common form of polycystic kidney disease, a condition with no cure.

This is the first treatment that targets a mechanism that directly contributes to the development and growth of the kidney cysts in autosomal dominant polycystic kidney disease

The results of the trial demonstrated tolvaptan’s ability to intervene in a way that slows kidney function decline in this population.

“This is the first treatment that targets a mechanism that directly contributes to the development and growth of the kidney cysts in autosomal dominant polycystic kidney disease,” says Dr Vicente Torres, director of Mayo Clinic’s Translational Polycystic Kidney Disease Center. “This in effect means it may delay the need for a kidney transplant or dialysis in patients with this disease.”

Autosomal dominant polycystic kidney disease is an inherited condition that affects 1 in every 500 to 1,000 individuals in the U.S. This disease is found in all races and sexes. Autosomal dominant polycystic kidney disease, which is the fourth most common cause of end-stage kidney disease, requires dialysis or a kidney transplant.

The disease causes a slow but relentless growth of cysts that damage the kidneys. In addition to negatively affecting the quality of life, the condition also causes hypertension and painful complications. The cysts, which can damage kidneys with their size, can develop in other organs, especially the liver.

Approximately half of individuals with autosomal dominant polycystic kidney disease eventually will require dialysis or kidney transplant by age 60.

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RPS says pharmacists must always be present in pharmacies

The three RPS national boards have jointly called for legal guarantees that a pharmacist will always undertake a clinical assessment or check, and that there must be no legal loopholes that can bypass this requirement.

pharmacy counter patient pharmacist al 17

Source: Alamy.com

The leaked document, prepared by a working group of the Department of Health’s Rebalancing Medicines Legislation and Pharmacy Regulation Programme Board, suggested that current legislation could be changed to allow a registered pharmacy professional, which could include a technician, to take responsibility for the sale and supply of pharmacy and prescription-only medicines.

The Royal Pharmaceutical Society (RPS) has said it believes a pharmacist should always be present in a pharmacy, apart from occasional short periods of time.

Responding to a leaked document produced for the Department of Health (DH) on the issue of whether pharmacy technicians should be allowed to supervise pharmacies, the RPS has issued an eight-point position statement on the role of registered technicians supervising the sale and supply of medicines.

Read More: http://snip.ly/3pujp#http://www.pharmaceutical-journal.com/news-and-analysis/news/rps-says-pharmacists-must-always-be-present-in-pharmacies/20203609.article

Pharmacist in deadly meningitis outbreak heading to trial

Pharmacist in deadl

After watching his mother die from meningitis in a nationwide outbreak caused by contaminated steroids, Scott Shaw is determined to make sure something like that never happens again.

A stiff punishment for the Massachusetts pharmacist Shaw believes is partially responsible may help, he says.

“I believe as surely as I’m talking to you right now that if something isn’t done, we will repeat this again,” the North Carolina man said.

Glenn Chin, the supervisory pharmacist at the now-closed New England Compounding Center in Framingham, about 22 miles (35 kilometers) west of Boston, is to go on trial Tuesday for his role in the 2012 fungal meningitis outbreak that killed 76 people and sickened hundreds of others.

Chin faces up to life in prison if convicted of all counts of second-degree murder under federal racketeering law.

Experts, and Chin’s defense attorney, believe prosecutors have a stronger case against Chin than they did against the co-founder of the compounding pharmacy, Barry Cadden. Cadden was sentenced in June to nine years in prison after being acquitted of second-degree murder charges but convicted on conspiracy and fraud charges.

Chin ran the so-called clean rooms where steroid injections were made. He is accused of failing to properly sterilize the drugs, among other things. Chin also faces conspiracy, mail fraud and other charges.

“I’m just a little concerned that the judge and the jury might be a little more harsh on Glenn Chin because he was doing the work in the clean room,” Chin’s attorney, Stephen Weymouth, said.

Throughout Cadden’s trial, the co-founder’s lawyers tried to push the blame onto Chin. Chin intends to point the finger back at Cadden.

Weymouth said he will argue that Chin was essentially a “puppet” for Cadden, who made working in the clean rooms so difficult that “mistakes might have been made.” Cadden was the one calling the shots and pushing the orders to line his own pockets, Weymouth said.

 

Read More: http://snip.ly/kx5et#http://abcnews.go.com/US/wireStory/pharmacist-deadly-meningitis-outbreak-heading-trial-49907214

Pharmaceutical companies gave $12m to doctors, nurses and pharmacists

Pharmaceutical companies gave $12m to doctors, nurses and pharmacists.jpg

Pharmaceutical companies gave Australian doctors, nurses and pharmacists almost $12m in fees and expenses to attend conferences and give talks between November 2016 and April 2017.

The payments comprised more than $6.5m for travel expenses and accommodation; more than $4.2m in speaking and consultancy fees; and more than $700,000 to cover registration at medical conferences and events.

The drug companies Bristol-Myers Squibb and Amgen both spent more than $1m over the six months and one doctor received more than $39,000.

Health economists Prof Philip Clarke from the University of Melbourne and Dr Barbara de Graaff from the Menzies Institute for Medical Research in Tasmania conducted an analysis for Guardian Australia on the $11,667,253 in pharmaceutical payments made to healthcare professionals.

Under the updated Medicines Australia code of conduct, pharmaceutical companies were required to disclose all payments made to healthcare professionals by 29 August. Previously, this disclosure required the consent of the health practitioners, which in many cases

 

Read More information: http://snip.ly/mulqf#https://www.theguardian.com/australia-news/2017/sep/12/pharmaceutical-companies-gave-12m-to-doctors-nurses-and-pharmacists