Blog - Page 4 of 13 - Executive Conference Corporation Webinars

USP/FDA Microbiological Non-Compliance Issues in a Biopharmaceutical/Pharmaceutical Environment

Wednesday December 4, 2019
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

USP/FDA Microbiological Non-Compliance Issues often represent observed problems that occur with both non-sterile and sterile products in controlled and classified environments as well as within the microbiological laboratory. Various regulators will cite firms for these non-compliance issues under a variety of different sections of the Code of Federal Register (CFR) to include 21 CFR 211.113(a) and (b), 211.84(d)(6), 211.165(b), and 211.192. Non-compliance issues are also cited as per United States Pharmacopeia to include USP<51>, <60>, <61>, <62>, <71>, <1072>, <1111>, <1113> and <1116>. Also, various Guidances for Industry are also cited and often used within Observations. One of the most notable Guidances is the September 2004 FDA Guidance for Industry on Aseptic Processing.

Sterile Filtration of Pharmaceutical Products – Validation and Regulatory Requirements

Thursday December 5, 2019
1:00 pm – 2:00 pm EST

Instructor: Roger Cowan

Sterile filtration is one of the most critical steps in sterile pharmaceutical manufacture. This is because the filtration process provides assurance of sterility in the finished drug product.

Proper understanding and testing of the sterile filtration system according to international regulatory standards is important for both the validation and ongoing monitoring of the system.

It is important that the sterile filtration process is properly validated for your particular application. The process requirements and validation needs differ based on the filtration requirement. This webinar will give you a comprehensive understanding of this important subject with an emphasis on the different types of sterilizing filtration available and their application to your particular system. For example, the application of sterile filtration to use-point compressed air is discussed in detail.

GMPs for MICROBIOLOGISTS — The Manufacturing Environment

Tuesday December 10, 2019
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Executive Conference Corporation (ECC) is proud to present “GMPs for Microbiologists, The Manufacturing Environment”. Within a Manufacturing Environment, cGMP microbiological issues always arise that require addressing.

Whether the facility is considered to be a Controlled or Classified environment, whether it is manufacturing non-sterile or aseptically filled product, the Microbiology Environment of the product is critical to assuring products leave the facility with the microbiology specifications in control. As the facility is examined in additional detail, the environment also must be considered. Both airborne viable and non-viable particulate considerations must be explored and controlled within all areas from ISO 5 to 8. The water systems, which include potable water, purified water and water for injection, will also be explored regarding their specifications, maintenance, and compliance.

The Waiting Is Over – A New General Chapter, USP<60>, Burkholderia cepacia Is Here

Thursday December 12, 2019
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Burkholderia cepacia and its BCC Complex are bacterial species that are ubiquitous in nature and often found as a frequent recall issue based upon CDER data. Pharmaceutical products that are contaminated with B. cepacia and/or its Complex may pose serious issues to infants, elderly and immunocompromised individuals. Preventing B. cepacia contamination in drugs by addressing the potential sources of this bacterium in a drug manufacturing operation is an important public health goal.

Historically, when the USP was revised in May 2009, it was modified to include both USP<61> and USP<62>, and harmonized with both the European Union (EU) and Japanese Pharmacopeia (JP). B. cepacia was excluded at that time as a “specified” bacterium – even though many individuals believed that it should have been included. In addition, it was not included within USP<1111> when it also was modified several years ago. One of the main reasons that all believed that it should have been included was because of the frequency in which it occurs and the diversity of environments and products in which it has been found.

MICROBIOLOGY FOR THE NON-MICROBIOLOGIST — AND THE MICROBIOLOGIST WHO DESIRES A GMP MICROBIOLOGICAL REFRESHER

Tuesday January 7, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

With the increasing number of Regulatory Actions throughout North America to include Form FDA 483s and Warning Letters for both Active Pharmaceutical Ingredients (APIs) and finished product, it has become increasingly important for Companies and individuals, in particular, manufacturing both non-sterile and sterile final products, to have a basic understanding of microbiology — regardless of the Department in which they work. Every individual within varying Departments from Facilities to Manufacturing to Quality Control should understand the basics of microbiology and the issues that non-compliance can create. Recently, a large multi-national pharmaceutical company was cited for the second time by the FDA for not determining that mold was growing on the “clean side” of the HEPA filters in an ISO Class 5 environment after it had been identified by mechanics several years previously.

GMP Environmental Monitoring for Pharmaceutical Clean Rooms

Thursday January 9, 2020
1:00 pm – 2:00 pm EDT

Instructor: Roger Cowan

Environmental Monitoring looks at the end results of the Environmental Control program – the microbiological and particulate quality of the clean room.

As the FDA Guideline on Aseptic Processing GMP (2004) states:

“In aseptic processing, one of the most important laboratory controls is the environmental monitoring program. This program provides meaningful information on the quality of the aseptic processing environment (e.g., when a given batch is being manufactured) as well as environmental trends of ancillary clean areas. Environmental monitoring should promptly identify potential routes of contamination, allowing for implementation of corrections before product contamination occurs.”

Microbial Data Deviation Investigations — Latest FDA & ICH Requirements and Guidance

Tuesday January 14, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Microbial data deviation investigations come in a multiplicity of forms and may vary from the very simple to include the incubation of a plate at an incorrect temperature to attempting to determine the “root cause” of a sterility test failure. The resultant investigations and their data requirements may be very short in duration, e.g., a matter of only several to 40 – 50 hours. However, unlike chemical analytical deviations and their Out Of Specification (OOS) studies and Corrective/Preventive Action (CAPA) programs, the length of time to complete these microbiological investigation studies may extend to as many as six months based on the biological laboratory studies that may be required.

The question often arises as why my Company is experiencing these deviations? Very often the answer is simple laboratory errors that require minimal training to correct. In other situations personnel are experiencing difficulties with understanding the USP or the standard operating instructions (SOPs) from which these SOPs are derived. In still other situations, these problems are being caused by management, and personnel require their assistance to minimize these complex periodic issues.

THE BACTERIAL ENDOTOXINS TEST (ISSUES AND SOLUTIONS) — TO INCLUDE THE ISSUE OF LOW ENDOTOXIN RECOVERY (LER) AND TR 82 (PDA)

Thursday January 16, 2020
1:00 pm – 2:30 pm EST

Instructor: Barry A. Friedman, Ph.D

On Tuesday, July 12, 2011, the FDA posted on their web site a notice that they had withdrawn the 1987 Guideline on Validation of the Limulus Amebocyte Lysate Test as an End Product Endotoxin Test for Human Parenteral Drugs, Biological Products and Medical Devices. They advised that the 1987 Guideline is considered obsolete and does not reflect the Agency’s current thinking on the topic.

In lieu of this document, the FDA advised that they would be issuing a Guidance for Industry on Pyrogen and Endotoxins Testing: Questions and Answers during the November/ December 2011 timeframe. After much delay, this NEW Guidance was released in June 2012.

In addition, the FDA references three documents that they believe have more than offset the previous FDA Guidance that was withdrawn. They advise that these documents be referenced for the fundamental principles of the gel clot, photometric and kinetic test methods.

Best Practices for Cleaning Validation Swab Sampling and Recovery Studies

Thursday January 23, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Richard Forsyth

This Web Seminar will present a detailed overview of best practices for cleaning validation swab recovery and sampling for Active Pharmaceutical Ingredients (APIs) and detergents from product contact surfaces of equipment in the pharmaceutical industry. All aspects of swab sampling will be discussed with the emphasis on how swab sampling ties into the cleaning validation program.

Current regulatory expectations and how they impact swab recovery and sampling will be reviewed. Of note will be the expectations for acceptable recovery studies and concerns for instances of low recoveries.

The swab parameter phase evaluates the parameters necessary to clearly demonstrate that a swab sampling will accurately and consistently provide data that demonstrates a cleaning validation study is successful. The swab parameters are evaluated individually to assess their impact on swab data. The calculated cleaning limit directly impacts the swab parameters to be validated.

Monitoring of Bioburden – How to Manage and Control Contamination within Non-Sterile and Sterile Products

Thursday January 30, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Monitoring of in-process bioburden of pharmaceutical components, containers and closures, intermediates, drug substances and drug products is an essential element of the overall contamination control program for appropriate process control of both non-sterile and sterile products.

A typical bioburden control program includes review and analysis of potential sources of contamination commencing with each of the raw materials to include the Certificate of Acceptance of each. The microbiological contamination control program should be developed to identify and control bioburden and to assess product risk based on ICH Q9 Quality Risk Management. The bioburden risk assessment should result in the establishment of a range of critical control points which will ultimately lead to specifications for each raw material and to each unit operation as well as the drug substance (DS) and product (DP).

Risk Based Approach to Cleaning & Disinfection

Tuesday February 4, 2020
12:00 Noon – 1:00 pm EDT

Instructor: Jim Polarine

This seminar will cover the current industry regulations in the US, Europe and Globally related to cleaning and disinfection. Regulatory expectations will be covered including the latest revision of Annex I and recent FDA Warning Letters and 483’s related to cleaning and disinfection will be covered. The current antimicrobial products used in cleanroom industry will be discussed. Cleaning frequency, disinfectant rotation, rinsing and residue removal, disinfectant coverage calculations, and the most current equipment and methodologies for cleaning and discinfection will be covered in detail. The topic of sterility as it relates to cleanroom disinfectants and sporicides will be explained. This seminar will provide the audience with the ability to design and effective risk-based approach to cleaning and disinfection.

Good Laboratory Practices (GLP) vs. Good Manufacturing Practices (GMPs) — A Comparison and Contrast – “Why One Should Use Only GMP Facilities for Manufacturing and Testing”

Wednesday February 5, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Periodically one hears the comment that “a laboratory or a manufacturing facility meets 21 CFR Part 58 Good Laboratory Practices (GLP) and therefore they meet all of the cGMP requirements”. Contrary to popular belief, 21 CFR Part 58 is not the equivalent of 21 CFR 210/211 and does not meet the same requirements as 210/211. They (Part 58) do have the force of law and are not “watered down” GMPs.

Good Manufacturing Practices (cGMPs) represents that part of Quality Assurance that ensures that products are consistently produced and controlled to the Quality standard appropriate to their intended use and as required by the product specification. They fall within the requirements of 21 CFR Parts 210/211 and support final product requirements for humans and animals.

Antimicrobial Effectiveness (USP<51>) and Its Testing

Thursday February 6, 2020
1:00 pm – 2:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Nonsterile dosage products often use preservatives in their formulations to minimize the growth of microorganisms inadvertently introduced during or subsequent to the manufacturing process. Sterile products packaged in multiple-dose containers contain antimicrobial preservatives to inhibit the growth of microorganisms that may be introduced from the repeated withdrawal of individual doses.

Antimicrobial preservatives should not be considered as a substitute for good manufacturing practices (GMP), solely to reduce the viable microbial population of a nonsterile product or control the presterilization bioburden of a multidose formulation during manufacturing.

Antimicrobial effectiveness, whether natural within the product or produced with the addition of an antimicrobial preservative, must be demonstrated for all injections packaged in multiple-dose containers or for other products containing antimicrobial preservatives. Antimicrobial effectiveness must be demonstrated for aqueous-based, multiple-dose topical and oral dosage forms and for other dosage forms such as ophthalmic, otic, nasal, irrigation, and dialysis fluids.

Cleaning and Cleaning Validation

Tuesday February 11, 2019
12:00 Noon – 1:30 pm EST

Instructor: Richard Forsyth

This Web Seminar will present a comprehensive overview of the life-cycle approach to cleaning for product contact surfaces of equipment in the pharmaceutical industry. The four phases of cleaning : cleaning assessment, cleaning development, cleaning validation and cleaning monitoring will be discussed including how they contribute to a compliant, evolving cleaning program.

The cleaning assessment phase evaluates either the current cleaning procedure or a proposed change to the current cleaning procedure against the current regulatory cleaning validation expectations. Any necessary remediation strategy for the assessment is determined in order to define an efficient cleaning development study.

Regulatory Aspects of Microbiology in a Non-Sterile Environment

Tuesday February 18, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Non-sterile microbiology offers many challenging regulatory issues often not considered in aseptic manufacturing because the rules have historically been minimal when compared to aseptic manufacturing. These rules have included the handling and evaluation of non-sterile components, the environment and final product, but not to the extent of sterile products.

This 90 minute Executive Conference Corp. (ECC) webinar discusses various regulations and requirements and how they impact non-sterile manufacturing to include the setting of specification, development of the process, holding times, preservation issues, cleaning, sanitization and the requirements for the testing of recovered microorganisms. Water Activity, which was out of vogue, until recently, will also be reviewed. The “Art of Troubleshooting — Finding What Occurred”, will also be highlighted.

Risk Management of Raw Materials in a GMP Environment

Wednesday February 19, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Risk management of raw materials in a cGMP environment is an area that is often overlooked as a Company develops new products. Depending on the product being developed, e.g., tablets and capsules vs. biotechnology products, as few as fifteen to twenty raw materials or as many as sixty need to be sourced and accepted before the process can be moved from initiation through completion. This live, interactive presentation will extensively review this area. It will also delve into the renewed issue of microbial and endotoxin contamination of these raw materials and why the FDA, EMA and Health Canada have recently focused on them.

This live, interactive training webinar will also examine a variety of the issues surrounding raw materials to include what materials should be tested and to what extent during Phase 1, 2 and 3. It will cover testing requirements during each Phase and what may be optional until the product moves to its next Phase. It will determine what options exist — even within a Phase 2 or Phase 3 testing framework. It will discuss compendial vs. non-compendial testing and how to respond when no method is available. The presentation will also discuss how a 90 percent vs. a 90.0 percent minimum purity analysis can delay your initiation of testing. Further, it will consider packaging and storage requirements and their impact on in-coming materials to include both raw materials and API.

Process Simulation Testing for Aseptically Filled Products

Tuesday February 25, 2020
12:00 pm – 1:30 pm EST

Instructor: Barry A. Friedman, Ph.D

Sterile products may be broadly classified into two main categories based on their production mode — those that are terminally sterilized following the filling and sealing of the container and those that are aseptically sterilized, that is, filter sterilized as a bulk product, filled and then sealed. Aseptic processes play a critical role with large molecules that cannot be terminally sterilized. The verification of the process to produce sterile product is evaluated by the demonstration of various media fill process simulations that will vary in both numbers and size of the containers as well as the volumes filled over a defined period of time.

Products that have historically been aseptically filled have relied upon the use of USP <71> Sterility Tests to demonstrate sterility. However, since no more than 20 containers are tested per media regardless of the production lot size, the use of sterility tests does not provide a high degree of sterility assurance (SAL). Thus, media fills are now utilized to simulate the actual fills and to demonstrate at least a 10^-3 sterility assurance level of no contamination. If the facility uses RABS or isolators, a SAL of 10^-5 to 10^-6 is even possible since the interactions with personnel and the environment decrease markedly.

Contamination Control Strategies: Facts and Sciences to Consider

Wednesday February 26, 2020
12:00 Noon – 1:00 pm EST

Instructor: Jim Polarine

This webinar will cover a risk-based approach to a cleaning and disinfection program and case studies in contamination control. Details will be provided on how to follow a risk-based approach for cleaning and disinfection using good science. The most common causes of contamination will be conveyed in case studies with fungal spore, bacterial spore, and Deinococcuscontamination. Solutions will be discussed on how to proactively prevent contamination from reoccurring.

The Microbiology of Water in a GMP Environment

Thursday March 12, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Knowledge of the microbiology of water in a GMP environment is critical to the health of any water system being used to produce a pharmaceutical or biotechnology product. Even companies manufacturing tablets need to be aware of the quality of the water that may be contacting their process or product. The well-being of a facility revolves around the health of each water system within that facility. How often have we learned of a facility being closed for weeks at a time because of a water system that has exceeded its microbiological specifications?

This live, interactive Executive Conference Corp. (ECC) training webinar presentation will also examine a variety of the issues surrounding water in a facility to include the testing of each water source and to what extent. It will cover testing requirements during commissioning and testing on an on-going basis. The webinar will examine Quality Risk Management (ICH Q9) and discuss how a properly developed Facility Water Validation Plan may lead to a logical, reduced requirement for testing vs. time.

CMO Supplier Quality Agreements – How to Comply with new FDA and EU Guidelines for Contract Drug Manufacture

Thursday March 12, 2020
2:00 pm – 3:00 pm EDT

Instructor: Roger Cowan

In 2010, the global CMO market was estimated at $26 billion dollars. Year on year growth has been 10.7% since 2008. The increasing use of outsourcing in the pharmaceutical industry along with recent well publicized quality issues with CMOs, make it a necessity to have excellent quality oversight of external manufacturers to provide assurance of GMP compliance. A Quality Agreement is one tool used to accomplish this objective.

A Quality Agreement is a contract between a pharmaceutical firm and a GMP Contract Manufacturer detailing the responsibilities of each party in assuring the quality, safety and efficacy of the manufactured drug.

Recently, the EU and the FDA issued regulatory guidance to bring some clarity and consistency to these quality contracts:

EU GMP Chapter 7 “Outsourced Activities” (Revised)
Guidance for Industry “Contract Manufacturing Arrangements for Drugs: QualityAgreements”

The Waiting Is Over – A New General Chapter, USP<60>, Burkholderia cepacia Is Here (December 2019 issued)

Thursday March 19, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Burkholderia cepacia and its BCC Complex are bacterial species that are ubiquitous in nature and often found as a frequent recall issue based upon CDER data. Pharmaceutical products that are contaminated with B. cepacia and/or its Complex may pose serious issues to infants, elderly and immunocompromised individuals. Preventing B. cepacia contamination in drugs by addressing the potential sources of this bacterium in a drug manufacturing operation is an important public health goal.

Historically, when the USP was revised in May 2009, it was modified to include both USP<61> and USP<62>, and harmonized with both the European Union (EU) and Japanese Pharmacopeia (JP). B. cepacia was excluded at that time as a “specified” bacterium – even though many individuals believed that it should have been included. In addition, it was not included within USP<1111> when it also was modified several years ago. One of the main reasons that all believed that it should have been included was because of the frequency in which it occurs and the diversity of environments and products in which it has been found.

Grouping Products and Equipment for Cleaning Validation and Selection of Worst-Case Parameters for Efficient Cleaning Validation Execution

Tuesday March 24, 2020
12:00 Noon – 1:30 pm EST

Instructor: Richard Forsyth

This Web Seminar will present a comprehensive overview of the product grouping and equipment grouping for cleaning validation (CV) for product contact surfaces of equipment in the pharmaceutical industry. Grouping of products and equipment are necessary in a multi-product facility to develop a comprehensive, understandable, executable and maintainable cleaning validation program.

Product grouping is used to identify the product(s) for CV execution. The selection criteria are critical to justify a defendable product grouping. Although a number of criteria are available, the two recommended criteria to use are: hardest-to-clean product and the product with the lowest cleaning limit.

The hardest-to-clean criterion is based on the physical properties of the formulation components and the proportion of each component in the formulation. In an aqueous or detergent based cleaning medium, hydrophilic, water soluble components are relatively easy to clean, whereas hydrophobic formulation components are more difficult to clean.

DEVELOPING THE KEY ELEMENTS OF A PROCESS VALIDATION PLAN

Wednesday March 25, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Whether a Company is developing a new product or facility, the issue of developing the key elements of a comprehensive Validation Package is essential to assure the timely completion of all activities. A Validation Package is designed to satisfy both current domestic and international regulations, guidelines and policies for active pharmaceutical ingredients (APIs), drugs (FP), biologics and devices and to verify equipment systems, utilities, software and processes are properly designed (DQ), installed (IQ), operate (OQ) and perform (PQ) in a consistent and controlled manner.

The purpose of validation is to assure the facility, manufacturing process, and supporting services are capable of supporting the manufacture of pharmaceutical and device products that consistently meet their predetermined quality attributes. The Validation Master Plan (VMP) uses a “life cycle” approach and emphasizes Quality Risk Management (ICH Q9) as the Plan proceeds from validation through verification and qualification. The VMP is intended to project a picture of how your company has integrated current Good Manufacturing Processes (cGMP) as promulgated in 21 CFR Part 820 and 211 into all aspects of the manufacturing process. The Validation Program is designed to proactively assure GMP compliance from facility development through the distribution of final product.

FDA Regulatory/Industry Practices and the Microbiological Fallacies Associated with Them

Thursday March 26, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Biotechnology/Pharmaceutical/Microbiological Urban “Fallacies” have created a very interesting landscape for many years. As personnel turnover continues to occur within the pharmaceutical/biotechnology arena, these Urban “Fallacies” again are thriving. Often the term that one hears is “standard industry practices” – but what does it mean? Does this infer that the “practices” are sanctioned by the government or industry? And, do they really represent cGMP?

In addition, many misunderstandings occur within USP, EP, FDA Guidances, and other governmental/regulatory documents that were issued many years ago. In some instances, a recent change that was made within a USP Chapter or FDA Guidance creates a misunderstanding because of a long history behind the original document and a lack of knowledge of where their contents originated.

Development of a Steam Autoclave Sterilization Validation Plan

Tuesday March 31, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Terminal moist heat sterilization is presently considered the method of choice to ensure sterility. All aqueous-based sterile products are subject to terminal moist heat sterilization unless the sterilization, itself, will degrade the product. This interactive, live Executive Conference Corp. (ECC) webinar is intended to provide manufacturers of pharmaceutical dosage forms as well as components (vials and stoppers) with guidance to establish the scientific effectiveness of moist heat sterilization processes. It has been developed as an overview of the elements of moist heat sterilization processes requiring evaluation, and describes approaches to effectively accomplish this.

This guideline, derived from Health Canada guidances, specifies the minimum documentation required to certify that moist heat sterilization processes have been thoroughly evaluated and are adequately controlled and validated.

Risk Factors Involved in the Development and Implementation of an Environmental Monitoring Strategy for a Controlled/Classified Environment

Thursday April 2, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Environmental monitoring of controlled and classified environments and their systems is required to maintain compliance with EMA/FDA/Health Canada requirements. To perform this task, knowledge of the fundamentals of the systems and their requirements is a must. Doing this requires the ability to identify the “key” elements of the Monitoring Program. Understanding the regulations and the regulatory expectations must be accomplished to assure that all of the necessary SOPs, appropriate specifications and testing are developed, implemented and met. Relying on obtaining from others that a procedure must be executed in a specific way to “meet industry standards” or “meet industry expectations” leads only to disastrous consequences. Learning what documents form the foundation is required for the knowledge base.

The necessary regulatory documents must be in place and translated into the various SOPs. Both non-sterile and sterile production facilities must possess these documents. Significant source documents include ISO 14644, Annex 1 (revised March 2009), FDA’s Aseptic Processing Guidance document (September 2004), USP 1116 (revised May 2012), etc.

Current and future trends in Lyophilization: Optimal Formulation Design for a Lyophilized Product

Tuesday April 7, 2020
12:00 pm – 1:30 pm EDT

Instructor: J. Jeff Schwegman, Ph.D

It is not uncommon for formulation development scientists to think of lyophilization as the “black box” of the manufacturing process. Once the Development group has finished with a new formulation, it can simply be passed to Manufacturing for implementation. In many cases, development scientists don’t even speak with the manufacturing group to know what the equipment limitations are when producing a lyophilized product. This has resulted in cases where formulations have been developed that cannot be freeze-dried at all, or cannot be scaled up, which means that the product has to go back to the formulation group to be re-engineered. This wastes valuable time in the new drug development process and can result in the approval and or release date of the drug to be delayed.

GMPs for MICROBIOLOGISTS — The Manufacturing Environment

Wednesday April 8, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Executive Conference Corporation (ECC) is proud to present “GMPs for Microbiologists, The Manufacturing Environment”. Within a Manufacturing Environment, cGMP microbiological issues always arise that require addressing.

Whether the facility is considered to be a Controlled or Classified environment, whether it is manufacturing non-sterile or aseptically filled product, the Microbiology Environment of the product is critical to assuring products leave the facility with the microbiology specifications in control. As the facility is examined in additional detail, the environment also must be considered. Both airborne viable and non-viable particulate considerations must be explored and controlled within all areas from ISO 5 to 8. The water systems, which include potable water, purified water and water for injection, will also be explored regarding their specifications, maintenance, and compliance.

HVAC and GMP Environmental Control – for Pharmaceutical Clean Rooms

Thursday April 16, 2020
1:00 pm – 2:00 pm EDT

Instructor: Roger Cowan

Environmental control of pharmaceutical clean rooms is essential to the manufacture of a quality product. The definition of Environmental Control vs. Environmental Monitoring is discussed. Control of such conditions as airborne particulate, microorganisms, temperature, humidity, differential pressure, airflow, air velocity and personnel is crucial to protect the product from contamination.

Therefore, the design, validation and ongoing monitoring of a clean room HVAC system is necessary to assure the quality and safety of the pharmaceutical product.

Also, a proper understanding and testing of the clean room environment according to international regulatory standards is important from a compliance perspective.

It is important that a clean room’s HVAC system is fully understood, properly designed and properly validated. If this is accomplished, it will provide the environmental control necessary to meet the regulatory particulate and microorganism levels necessary to manufacture quality pharmaceutical product.

Derouging and Passivation of Stainless Steel Equipment

Tuesday April 21, 2020
12:00 pm – 1:30 pm EDT

Instructor: Paul Lopolito

Pharmaceutical facilities as they age experience some level of corrosion resulting in rouged stainless steel equipment. There are several factors that can contribute to rouge formation including presence of halides, oxidizing chemistries, extreme pH’s, high temperatures, dissimilar metallurgy, defects, improper welding and inadequate passivation. Rouge on stainless steel increases surface roughness which can reduce cleanability, sanitization, contamination control practices and equipment life expectancy.

TERMINALLY STERILIZED PHARMACEUTICAL PRODUCTS—PARAMETRIC RELEASE (NEW USP<1222>, November 2019) AND ITS RELATIONSHIP TO THE NEW BRITISH TERMINAL STERILIZATION METHODOLOGY (March 2019)

Wednesday, April 22, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Parametric release is defined as the release of terminally sterilized batches or lots of sterile products based upon compliance with the defined critical parameters of sterilization without having to perform the requirements under USP<71> Sterility Tests.

Parametric release becomes possible when the mode of sterilization is 1) very well understood, 2) the physical parameters of processing are well defined, predictable, and measurable, 3) and the lethality of the cycle has been microbiologically validated through the use of appropriate biological indicators or, in the case of ionizing radiation, the appropriate microbiological and dosimetric tests.

The use of parametric release for sterilization processes requires prior FDA approval. It should be expected that the regulatory agencies evaluating submissions including the use of parametric product release would insist upon a well supported scientific rationale for the sterilization process and well documented validation data.

Contamination Control: Common Myths and Urban Legends in the Pharmaceutical Industry

Thursday April 23, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Jim Polarine

Sterility is one of the most critical quality attributes that all parenteral products must possess; yet, it is one of the most difficult to consistently demonstrate to regulators. This presentation will discuss four (4) of the most common myths related to one of key sterility assurance programs to ensure qualified environments remain in a state of microbiological control. This session will be an effort to dispel many of the myths that still exist in the cleanroom today:

USP/FDA Microbiological Non-Compliance Issues in a Biopharmaceutical/Pharmaceutical Environment

Tuesday April 28, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

USP/FDA Microbiological Non-Compliance Issues often represent observed problems that occur with both non-sterile and sterile products in controlled and classified environments as well as within the microbiological laboratory. Various regulators will cite firms for these non-compliance issues under a variety of different sections of the Code of Federal Register (CFR) to include 21 CFR 211.113(a) and (b), 211.84(d)(6), 211.165(b), and 211.192. Non-compliance issues are also cited as per United States Pharmacopeia to include USP<51>, <60>, <61>, <62>, <71>, <1072>, <1111>, <1113> and <1116>. Also, various Guidances for Industry are also cited and often used within Observations. One of the most notable Guidances is the September 2004 FDA Guidance for Industry on Aseptic Processing.

Combination Products Regulatory Expectations and the FDA’s Latest Codification of the Applicable cGMP Requirements (To Include New “Bridging DRAFT Guidance” 12/19)

Thursday April 30, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Historically, the absence of clear cGMP requirements for Combination Products has resulted in inconsistent application as to the applicable Agency Center to submit product for review. Products for both CDER and CDRH as the primary Agency contact point may have historically been submitted to the incorrect organization for review because of a lack of knowledge as to the Primary Mode of Action (PMOA) of the product. While some of these product applications might have been relatively easy to discern, e.g., a
pre-filled syringe (usually CDER), other products may have had great difficulty finding the “correct home”.

Regulatory Aspects of Microbiology in a Non-Sterile Environment

Wednesday May 6, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Non-sterile microbiology offers many challenging regulatory issues often not considered in aseptic manufacturing because the rules have historically been minimal when compared to aseptic manufacturing. These rules have included the handling and evaluation of non-sterile components, the environment and final product, but not to the extent of sterile products.

This 90 minute Executive Conference Corp. (ECC) webinar discusses various regulations and requirements and how they impact non-sterile manufacturing to include the setting of specification, development of the process, holding times, preservation issues, cleaning, sanitization and the requirements for the testing of recovered microorganisms. Water Activity, which was out of vogue, until recently, will also be reviewed. The “Art of Troubleshooting — Finding What Occurred”, will also be highlighted.

FDA Contract Manufacturing Arrangements for Drugs: Quality Agreements — Their Relationship to Microbiological Issues

Tuesday May 12, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Non-sterile microbiology offers many challenging regulatory issues often not considered in aseptic manufacturing because the rules have historically been minimal when compared to aseptic manufacturing. These rules have included the handling and evaluation of non-sterile components, the environment and final product, but not to the extent of sterile products.

This 90 minute Executive Conference Corp. (ECC) webinar discusses various regulations and requirements and how they impact non-sterile manufacturing to include the setting of specification, development of the process, holding times, preservation issues, cleaning, sanitization and the requirements for the testing of recovered microorganisms. Water Activity, which was out of vogue, until recently, will also be reviewed. The “Art of Troubleshooting — Finding What Occurred”, will also be highlighted.

Current Trends in the Industry in Disinfectant Rotation and Residue Removal

Wednesday May 13, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Jim Polarine

This seminar will cover current trends globally in disinfectant selection and rotation in cleanroom operation. Regulatory expectations from FDA, MHRA, HPRA, CFDA, and ANVISA will also be covered and discussed with respect to rotation and rinsing strategies. Residue removal and rinsing strategies will be covered for cleanroom operations as well as case studies on rinsing and residue removal. This seminar will be beneficial for cleanroom managers and cleanroom operators as well as other cleanroom professionals.

Pharmaceutical Compressed Air – Quality GMP Standards and Requirements

Thursday May 14, 2020
1:00 pm – 2:00 pm EDT

Instructor: Roger Cowan

Compressed air for pharmaceutical use is considered a critical utility as many of its applications involve direct contact with the pharmaceutical product.

The design, construction and monitoring of a compressed air system is essential for maintaining a quality system without contamination of the product.

Proper testing of compressed air quality according to international standards is important for both validation and ongoing monitoring of the system.

Compressed air is often overlooked as a potential source of clean room and product contamination. This webinar will give you an understanding of the different types of contamination inherent in compressed air and how to prevent each from affecting your particular system.

Antimicrobial Effectiveness (USP<51>) and Its Testing

Tuesday May 19, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Nonsterile dosage products often use preservatives in their formulations to minimize the growth of microorganisms inadvertently introduced during or subsequent to the manufacturing process. Sterile products packaged in multiple-dose containers contain antimicrobial preservatives to inhibit the growth of microorganisms that may be introduced from the repeated withdrawal of individual doses.

Antimicrobial preservatives should not be considered as a substitute for good manufacturing practices (GMP), solely to reduce the viable microbial population of a nonsterile product or control the presterilization bioburden of a multidose formulation during manufacturing.

Visible Residue Limit Determination and Ruggedness

Wednesday May 20, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Richard Forsyth

This Web Seminar will present a comprehensive overview of the use of Visible Residue Limits (VRLs) for cleaning validation for product contact surfaces of equipment in the pharmaceutical industry. VRLs are the level below which no residue is visible under defined parameters and are applicable for cleaning validation when they are lower than the calculated cleaning acceptance limit.

VRLs can be established for APIs, products, excipients, and detergents as needed. Decreasing amounts of material are spiked onto coupons and dried. The dried coupons are viewed under defined viewing conditions by a number of observers, who determine the lowest level of material they can see. The VRL is the lowest level of material that all observers can see under the defined viewing conditions.

EMA’s New 2019 Guideline on Sterilization of Medicinal Products and its Potential Impact on FDA’s Sterilization Thinking

Thursday May 21, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

The European Medicines Agency (EMA) recently published “Sterilization of the Medicinal Product, Active Substance, Excipient and Primary Container” in March 2019 which has an effective date of October 2019. This new Guidance should have a dramatic impact on the FDA’s sterilization thinking since it strongly suggests that there are alternatives, i.e., Advanced Therapy Medicinal Products (ATMPs), to standard terminal sterilization standards of 121^oC for 15 minutes.

This new guidance discusses the choice of selective methods of sterilization of sterile products. It also reviews the use of terminal sterilization and the importance of alternative methods for manufacturing sterile products when terminal sterilization will cause degradation. Where terminal sterilization is not possible, an alternative must be developed that includes the rationale of ICH Q9 – Quality Risk Management. For new products, the guidance provides the appropriate decision-making process within several tables for the sterilization of various final product forms, e.g., aqueous, powder, pellets. Again, Quality Risk Management and its elements are essential to the decision-making process.

MICROBIOLOGY FOR THE NON-MICROBIOLOGIST — AND THE MICROBIOLOGIST WHO DESIRES A GMP MICROBIOLOGICAL REFRESHER

Thursday May 28, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

With the increasing number of Regulatory Actions throughout North America to include Form FDA 483s and Warning Letters for both Active Pharmaceutical Ingredients (APIs) and finished product, it has become increasingly important for Companies and individuals, in particular, manufacturing both non-sterile and sterile final products, to have a basic understanding of microbiology — regardless of the Department in which they work. Every individual within varying Departments from Facilities to Manufacturing to Quality Control should understand the basics of microbiology and the issues that non-compliance can create. Recently, a large multi-national pharmaceutical company was cited for the second time by the FDA for not determining that mold was growing on the “clean side” of the HEPA filters in an ISO Class 5 environment after it had been identified by mechanics several years previously

VALIDATION MASTER PLANNING (DEVELOPING A COMPREHENSIVE VALIDATION PACKAGE)

Thursday June 4, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Whether a Company is developing a new product or facility, the issue of a comprehensive Validation Package is essential to assure the timely completion of all activities. A Validation Package is designed to satisfy both current domestic and international regulations, guidelines and policies for active pharmaceutical ingredients (APIs), drugs, biologics and devices and to verify equipment systems, utilities, software and processes are properly designed (DQ), installed (IQ), operate (OQ) and perform (PQ) in a consistent and controlled manner.

The purpose of validation is to assure the facility, manufacturing process, and supporting services are capable of supporting the manufacture of pharmaceutical and device products that consistently meet their predetermined quality attributes. The Validation Master Plan (VMP) uses a “life cycle” approach and emphasizes Risk Management (ICH Q9) as the Plan proceeds from validation through verification and qualification. The VMP is intended to project a picture of how your company has integrated current Good Manufacturing Processes (cGMP) as promulgated in 21 CFR Part 820 and 211, into all aspects of the manufacturing process. The Validation Program is designed to proactively assure GMP compliance from facility development through the distribution of final product.

Lyophilization: Science based designs for optimal formulation and freeze-drying cycle development

Tuesday June 9, 2020
12:00 pm – 1:30 pm EDT

Instructor: J. Jeff Schwegman, Ph.D

Over the years, scientists have strived to understand and apply scientific principles to the formulation and process development of freeze-dried products. As opposed to using a “trial and error” approach, modern formulation and process development scientists have the information and tools necessary to design an optimal formulation and lyophilization cycle using a scientifically based empirical approach. By understanding the scientific principles and physical properties of the formulation and the lyophilization process, the development scientist can design a product that is produced in the most cost effective manner, in the least amount of time, is of the highest quality, and has adequate long term stability. Additionally, there have been many new and exciting technologies on the horizon, or in the early stages of implementation, in freeze-drying equipment. Several of these new technologies will be discussed in regards to both production-scale and development-scale freeze-dryers, and details on the advantages and or disadvantages of each will be discussed.

Risk Based Approach to Cleaning & Disinfection

Wednesday June 10, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Jim Polarine

This seminar will cover the current industry regulations in the US, Europe and Globally related to cleaning and disinfection. Regulatory expectations will be covered including the latest revision of Annex I and recent FDA Warning Letters and 483’s related to cleaning and disinfection will be covered. The current antimicrobial products used in cleanroom industry will be discussed. Cleaning frequency, disinfectant rotation, rinsing and residue removal, disinfectant coverage calculations, and the most current equipment and methodologies for cleaning and discinfection will be covered in detail. The topic of sterility as it relates to cleanroom disinfectants and sporicides will be explained. This seminar will provide the audience with the ability to design and effective risk-based approach to cleaning and disinfection.

Best Practices for Cleaning Validation, Swab Sampling and Recovery Studies

Thursday June 11, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Richard Forsyth

This Web Seminar will present a detailed overview of best practices for cleaning validation swab recovery and sampling for Active Pharmaceutical Ingredients (APIs) and detergents from product contact surfaces of equipment in the pharmaceutical industry. All aspects of swab sampling will be discussed with the emphasis on how swab sampling ties into the cleaning validation program.

Current regulatory expectations and how they impact swab recovery and sampling will be reviewed. Of note will be the expectations for acceptable recovery studies and concerns for instances of low recoveries.

The swab parameter phase evaluates the parameters necessary to clearly demonstrate that a swab sampling will accurately and consistently provide data that demonstrates a cleaning validation study is successful. The swab parameters are evaluated individually to assess their impact on swab data. The calculated cleaning limit directly impacts the swab parameters to be validated.

Microbial Data Deviation Investigations — Latest FDA & ICH Requirements and Guidance

Tuesday June 16, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Microbial data deviation investigations come in a multiplicity of forms and may vary from the very simple to include the incubation of a plate at an incorrect temperature to attempting to determine the “root cause” of a sterility test failure. The resultant investigations and their data requirements may be very short in duration, e.g., a matter of only several to 40 – 50 hours. However, unlike chemical analytical deviations and their Out Of Specification (OOS) studies and Corrective/Preventive Action (CAPA) programs, the length of time to complete these microbiological investigation studies may extend to as many as six months based on the biological laboratory studies that may be required.

Establishing Limits for Cleaning Validation

Thursday June 18, 2020
12:00 Noon – 1:30 pm EDT

Instructor: Paul Lopolito and Beth Kroeger

Cleaning validation is a key part of pharmaceutical, biopharmaceutical, and medical device manufacturing. One of the critical steps in performing a successful cleaning validation is establishing the limits of residue that can remain on the surface being cleaned. On 20 November 2014 the European Medicine Agency approved the “Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared equipment” which became effective on 01 June 2015.

THE BACTERIAL ENDOTOXINS TEST (ISSUES AND SOLUTIONS) TO INCLUDE THE ISSUE OF LOW ENDOTOXIN RECOVERY (LER) AND TR 82 (PDA) AND GENERAL INFORMATION CHAPTER <1085>

Tuesday June 23, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

On Tuesday, July 12, 2011, the FDA posted on their web site a notice that they had withdrawn the 1987 Guideline on Validation of the Limulus Amebocyte Lysate Test as an End Product Endotoxin Test for Human Parenteral Drugs, Biological Products and Medical Devices. They advised that the 1987 Guideline is considered obsolete and does not reflect the Agency’s current thinking on the topic.

In lieu of this document, the FDA advised that they would be issuing a Guidance for Industry on Pyrogen and Endotoxins Testing: Questions and Answers during the November/ December 2011 timeframe. After much delay, this NEW Guidance was released in June 2012.

Monitoring of Bioburden – How to Manage and Control Contamination within Non-Sterile and Sterile Products

Thursday June 25, 2020
12:00 pm – 1:30 pm EDT

Instructor: Barry A. Friedman, Ph.D

Monitoring of in-process bioburden of pharmaceutical components, containers and closures, intermediates, drug substances and drug products is an essential element of the overall contamination control program for appropriate process control of both non-sterile and sterile products.

A typical bioburden control program includes review and analysis of potential sources of contamination commencing with each of the raw materials to include the Certificate of Acceptance of each. The microbiological contamination control program should be developed to identify and control bioburden and to assess product risk based on ICH Q9 Quality Risk Management. The bioburden risk assessment should result in the establishment of a range of critical control points which will ultimately lead to specifications for each raw material and to each unit operation as well as the drug substance (DS) and product (DP).