Who are involved in filing investigational new drug applications

Lack of data integrity or the presence of anomalies in data is one of the primary reasons for which the FDA hauls up and penalizes an organization engaged in pharmaceutical manufacturing. As the use of analytical methods for drug quantification at many stages of drug development process grows in prevalence; the need for scientists, technicians, and quality assurance personnel, etc. to understand the complete validation process of the analytical method has become all the more important and necessary.

The validation of a method used is all the more important when it comes to dealing with quantitative analysis of drugs in various biological matrices such as blood, serum, plasma, cerebrospinal fluid, urine, tissues, etc. Yet, many companies overlook these crucial aspects of validation that are outlined in FDA’s guidance, and end up receiving citations from this regulatory agency for these reasons. A company which receives these citations not only faces the prospect of delayed drug development; it can also dent and jeopardize the future of the drug’s regulatory acceptance.

Clear understanding of FDA guidelines for bioanalytical method development and validation

A complete and clear understanding of the FDA guidelines for bioanalytical method development and validation is necessary to avoid being in situations outlined here. It is to familiarize pharmaceutical professionals with this important aspect of the FDA guidelines for bioanalytical method development and validation that Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will be organizing a webinar.

Venkata Kashyap Yellepeddi, who is an Assistant Professor of Pharmaceutical Sciences, College of Pharmacy, Roseman University of Health Sciences, Utah and Adjunct Assistant Professor, Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Utah; will be the speaker at this webinar. Please register for this webinar by visiting FDA guidelines for Bioanalytical

This webinar will offer intensive and detailed understanding of the bioanalytical method development and validation for drugs and nutraceuticals outlined in the FDA’s guidance. This learning will add immense value to sponsors and analysts representing industries who are involved in filing any of the following:

o  Investigational new drug applications (INDs)

o  New drug applications (NDAs)

o  Abbreviated new drug applications (ANDAs)

o  Biologic license applications (BLAs)

o  Supplements in developing bioanalytical method validation information used in human clinical pharmacology

o  Bioavailability (BA)

o  Bioequivalence (BE) studies that require pharmacokinetic (PK) or biomarker concentration evaluation

Analysts involved in bioanalytical methods used for nonclinical pharmacology/toxicology studies and for the veterinary drug approval process will also find this webinar highly valuable.

Matching the FDA’s level of expectations

The FDA expects anyone involved in quantification of drug using an analytical method in any stage of the drug development to be well-versed with FDA’s guidance for bioanalytical method validation. With this assumption, FDA inspectors often ask questions on analytical method validation during routine inspections, and expect all personnel involved to be knowledgeable about the process of validation. This webinar will familiarize participants with these aspects of an FDA inspection.

Kash will cover the following specific areas during this webinar:

o  Chromatographic Methods

o  Ligand Binding Assays

o  Parameters involved in Bioanalytical Method Validation

o  Data Analysis, Statistics and Reporting

o  Additional issues in Bioanalytical Method Validation.

This course is of high value to those involved in one or another way with bioanalytical method development and validation, such as Chromatographers, Analysts, Chemists, Scientists, Formulators, Patent Lawyers, Technicians in Pharmaceutical and Veterinary Industry, and Contract Research Representatives.

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FDA Warns on Mixing Opioid Addiction Treatments, Other Meds

TRENTON, N.J. (AP) — The Food and Drug Administration issued new warnings Wednesday about the dangers of combining medication for opioid addiction with anti-anxiety medicines and other drugs that also slow breathing and brain activity.

The FDA warned that mixing such drugs can cause difficulty breathing, coma or death, so it should be done with caution.

The agency said a growing number of people fighting opioid addiction with methadone or buprenorphine also take other prescription drugs that slow action of the central nervous system. The warning lists several dozen brand-name and generic drugs that could be risky, including Ambien and Lunesta for insomnia, Valium and Xanax for anxiety, muscle relaxers Soma and Zanaflex and antipsychotic drugs Abilify, Invega, Saphris and others.

The agency stressed that treating opioid addiction with medication can outweigh those risks and is crucial to curbing the U.S. opioid epidemic, along with counseling, rehabilitation and other support.

“Careful management of the patient and coordination of care is recommended,” rather than denying use of methadone or buprenorphine, FDA Commissioner Scott Gottlieb wrote in a statement issued with the warning.

The FDA recommends that doctors develop detailed treatment plans, warn patients on addiction treatments about the dangers of taking multiple drugs that depress brain activity, try tapering them off those other drugs and monitor them with blood and urine testing.

Buprenorphine and methadone work by binding to the same brain areas as opioids, reducing cravings and withdrawal without producing a high. The FDA is requiring makers of those two medications to update their package inserts with information about the risks of using them with other drugs.

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Q7 and Other Requirements for Active Pharmaceutical Ingredient (ASM) GMP

In late 2016, the FDA published the revised the Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, Guidance for Industry. The aim of this revision is to address Good Manufacturing Practices (GMPs) for a Quality Management System for Active Pharmaceutical Ingredients (API’s). Another of its aims is to help companies ensure that they meet the requirements of API quality and purity characteristics. While replacing Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients; this guidance amends the International Council for Harmonization (ICH) codification from Q7A to Q7.

All aspects of API manufacture are addressed by this revised guidance. These include:

o  The principles set out for Quality Management

o  The quality unit’s responsibilities

o  Activities relating to production

o  Internal audits

o  Product quality reviews

o  Qualifications expected from personnel

o  Their hygiene standards

o  The qualification that consultants need to have.

The GMP requirements for facility design and construction and equipment used are also included in this FDA Q7 GMP guidance for API revision. Several other API manufacturing topics are also part of this revision. Some of these include:

o  Management of materials

o  Process controls

o  Laboratory controls

o  Packaging

o  Storage and distribution

o  Validation

o  Change Control.

Clarity on the FDA’s revised standard

A webinar from Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will explain the FDA’s API Quality System revision in detail.

Eyal Lerner, owner of ELC Consulting Services which offers the pharmaceutical and medical devices industries support in all quality related issues, will be the speaker at this webinar. To gain understanding of how to apply the FDA’s revised API Quality Systems GMP requirements; please register for this webinar by visiting API (ASM) GMP

Explanation of API quality requirements

This webinar will explain the basic requirements and fundamentals of API QS. It will review the quality requirements for API in accordance to global API GMP- ICH Q7. The explanations will be based on practical experience and other relevant guidelines. Eyal will review the requirements of FDA and EMA. All the areas such as materials, Active Pharmaceutical Ingredient and Advanced Starting Materials (ASM) will be discussed along with their definitions. He will also explain the distinctions between these.

Administrative issues such as registration issues concerning filling, annual review and change report to file would be discussed. In this section, Eyal will lay emphasis on the section: “Registration standard: Common Technical Document (CTD)”, as it relates to the ICH M4.

Anyone, whose work concerns the area of development and manufacture of API, such as those in R&D, Regulatory Affairs, Quality Assurance and Quality Control, who wish to get an in-depth background and understanding of API QS; will find this webinar valuable.

A common technique plots the data to help detect trends, cycles, and shifts

Some of the functions of medical device manufacturers include:

o  Analyzing complaints

o  Processing data

o  Evaluating nonconformances

o  Utilizing other quality data sources.

The main purpose of this analysis, done using appropriate statistical methodology, under §820.100, is to identify the cause of nonconforming products and other quality problems. Time series analysis is one such family of these tools. Also called trending analysis, time series analysis uses visual methods to plot data over time.

A common technique plots the data to help detect trends, cycles, and shifts. The major use of these valuable methods is that they can help anticipate problems before they occur and demonstrate the effectiveness of corrective actions.

A webinar from Compliance4All on time series analysis

Dan O’Leary, President of Ombu Enterprises, LLC, a company offering training and execution in Operational Excellence, focused on analytic skills and a systems approach to operations management, will be the speaker at a webinar that analyzes time series analysis. This webinar is being organized by Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance.

Please visit methods when the data has a time based order to register for this webinar on time series analysis.

Full explanation of time series analysis

At this session, Dan will explain the graphical methods. In addition, he will also demonstrate some analysis techniques using Excel. Some special cases including data smoothing using moving averages, analysis with a lag function, and statistical process control (SPC), will be explained. By attending this webinar, participants will be able to gain understanding of time series analysis and some Excel capabilities to help perform the analysis. These tools are valuable for improvement projects and reporting information to management.

When the appropriate method is not clear, data analysis can be difficult. At this webinar, Dan will explain the methods when the data has a time based order. Excel includes functions and methods that can one can use to analyze the data and present it in a meaningful way.

Meaningful objectives

In this webinar, which will be of immense use to professionals who use statistics in their quality requirements, such as Quality Engineers, Manufacturing Engineers, Design Engineers, Data Analysts, Auditors, CA&PA Specialists, and Quality Managers; Dan will impart the following objectives:

o  Using run (trend) Charts

o  Determining a Linear Trend

o  Data Smoothing (Moving Averages and Lag Functions)

o  Using variables Control Charts(x-bar & R).

A clear process for compliant laboratory OOS investigations

The core of successful operation by a drug maker is laboratory testing. current Good Manufacturing Practices (cGMP) regulations require a drug manufacturer to use laboratory testing as a tool to validate that everything that goes into a laboratory product, such as in-process materials, finished materials, and containers adhere to set specifications. When all these are done, a major challenge for laboratories is in how to deal with a test that shows an Out of Specification (OOS) result.

Out of Specification results are viewed very seriously by the FDA

The FDA is uncompromising when it comes to dealing with Out of Specification results in laboratories. Its inspections of laboratory operations are very meticulous. It requires complete adherence to its guidances on how the laboratory has to investigate its Out of Specification and Out-of-Tolerance observations.

The ways by which finished Out of Specification products have to conform to set specifications, safety standards and other quality standards are specified in cGMP regulation Sec 211.165. Any lab whose result fails to do this gets summarily rejected. Another iteration of these cGMP regulations is that any unexplained deviation from the set specifications of a batch or its contents, whose test results show an Out of Specification result, will be subject to thorough investigation. Whether batches have only been manufactured and are yet to be distributed, or already are; the same rule applies.

Ways of dealing with Out of Specification results

This is the protocol that the cGMP regulation makes for dealing with Out of Specification testing:

o  Out of Specification testing is mandatory for the release of a test batch

o  The batch in which an Out of Specification result is confirmed gets rejected

o  The company’s Quality Assurance (QA) will have to state the reasons for the release of a batch that has an element of ambiguity in the result, and has to justify it.

The requirement that current Good Manufacturing Practices need to go into the manufacture of both active pharmaceutical ingredient and finished pharmaceuticals is stated in Section 501(a) 2 (b) of cGMP guidelines on Out of Specification. Also, all aspects such as active pharmaceutical ingredients, raw material testing, in-process and stability testing and Process Validation come under the ambit of the cGMP guidelines.

The FDA guidance on Out of Specification relates to the following products:

o  Human drugs

o  Combination products

o  Biology and biotechnological products

o  Type A medicated articles

o  Transplantation of human tissues

o  Finished products & active pharmaceutical ingredients

o  Medicated feed

o  Dietary supplements

o  Veterinary drugs

Out of Specification needs to be understood fully first

A reading of the above attests to the fact that a thorough understanding of the nature of the issues relating to Out of Specification results needs to be made for a laboratory to meet the required results. All the concerned persons should have complete knowledge of the FDA expectations for Out of Specification results.

It is this knowledge that needs to be applied to put in place procedures that define a complete, scientifically sound investigation of each Out of Specification and Out-of-Trend laboratory observation, as well as for establishing evidence that laboratory personnel conform to the procedures.

A proper learning session on dealing with Out of Specification results

A webinar from Compliance4All, a leading provider of cost-effective professional trainings for all the areas of regulatory compliance, will be providing learning on these aspects.

Jerry Lanese, an independent consultant who focuses on Quality Systems and the components of an effective Quality System, will be the speaker. Please visit Out-Of-Specification Laboratory Results to enroll for this highly educative session.

Tools for dealing with Out of Specification results

The speaker of this webinar will help participants build a basis for the implementation of adequate procedures that help avoid Out of Specification results. He will also review existing procedures and practices. Any laboratory personnel, who need understanding of the steps that a compliant laboratory has to take to handle the investigation of Out of Specification test results, will find this session very useful.

The ways in which the laboratory has to interface with other units through the laboratory investigation process will be explained. The speaker will dwell mainly on the FDA guidance on handling OOS laboratory results and will suggest a clear process for compliant laboratory Out of Specification investigations.

The following areas will be covered at this webinar:

o  Why the regulators are concerned about the handling of OOS investigations

o  The FDA model for handling OOS investigations

o  Commonly accepted terminology such as repeat testing and retesting

o  How the laboratory can meet regulatory expectations for OOS investigations.

o  The interaction between the laboratory and other units in the organization.

How to Recognize the Hazards of Blood Borne Pathogens

Bloodborne pathogens are those microorganisms present in the human blood that carry infection. These infections can cause disease in humans. The major bloodborne pathogens that cause infections in humans are:

o  Hepatitis B (HBV)

o  Hepatitis C (HCV)

o  Human immunodeficiency virus (HIV)

Although these are the main disease causing pathogens; there are many more. So, hospital staffs who deal with patients who are infected by bloodborne pathogens need to take extra care with regard to cleanliness and hygiene, since their chances of exposure to these pathogens are extremely high.

Apart from healthcare workers, other vulnerable populations that could come into contact with bloodborne pathogens consist of emergency workers, who are usually the first responders to people with these infections, and housekeepers who are required to maintain the bedding and other paraphernalia of people with bloodborne pathogens.

 

 

Detailed regulations from the CDC

Needless to say, regulatory agencies prescribe a heavy dose of regulation for the way in which to handle bloodborne pathogens, whether it is patients or the materials related to them that are being handled. Prominent agencies and departments that have guidelines on these aspects include the Centers for Disease Control and Prevention (CDC) and Occupational Safety and Health Administration (OSHA). Both OSHA and the CDC have guidelines on how workers at healthcare settings, who come into contact with patients with bloodborne pathogens, need to take safety precautions. The guidelines set out by the CDC cover all aspects of preventing bloodborne pathogens, such as:

o  The number of individuals in the patient population that are infected by bloodborne pathogens

o  The type of blood contact and its numbers

o  The particular pathogen that is involved

o  The nature of the exposure and the amount of blood in it

o  The virus in this exposed blood

The CDC guidelines are given to employers on how to they need to tackle bloodborne pathogens taking these factors into consideration. Important preventive steps that need to be taken, in line with the guidelines set out by both the CDC and OSHA include:

o  Use and disposal of needle sticks

o  Taking care to prevent exposure to injuries from sharps

o  The right protective gear to be used, such as gloves, other kinds of protection for important parts of the body, the right kind of clothing to be used, and the proper ways of using them, so that infection may be prevented through the nose, eyes, skin or mouth

o  What to do when exposure occurs

o  How to implement the proper reporting procedures

o  How each of these bloodborne pathogens have to be dealt with separately

o  The proper use of vaccines, when present

o  The proper procedure for treatment, when infection happens due to exposure

o  How to prevent bloodborne pathogens from infecting pregnant women

Learn the ways of implementing the important guidelines

All the actual ways of going about implementing the guidelines set out by the CDC and OSHA will be the topic of a webinar that is being organized by Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance.

The speaker at this very valuable and important learning session is Danielle DeLucy, who owns ASA Training and Consulting, LLC which provides pharmaceutical and biologics-based companies with training and quality systems assistance in order to meet regulatory compliance.

Please register for this webinar by visiting Bloodborne Pathogen Safety

Making the biosafety program more effective

This webinar will offer complete learning on the best ways to approach biosafety and on how to implement an effective management program for blood borne infections, safety and health, laboratory safety, infectious material and blood infection. This session is particular useful for personnel who work in a laboratory exposed to viruses or bacteria that are biological hazards. Danielle will explain how to optimize their Biosafety program and offer them a framework for setting up a successful management policy.

Danielle will cover the following areas at this webinar, which personnel such as EHS Staff, Occupational Health Staff, Laboratory Staff, Team Leads, Supervisors, Managers and Business Owners will find very valuable:

o  Review the regulations and guidelines recommended by the Centers for Disease Control and Prevention (CDC) for work with biological materials and, specifically, with blood borne pathogens

o  Provide up to date information about what constitutes blood borne pathogens from infectious materials, as well as other potentially infectious materials

o  The webinar provide answers about how to prevent exposures, deal with spills or exposures should they occur, and the how to recognize the hazards of blood borne pathogens

o  A thorough description of the types of infections of concern for blood borne pathogens, how one might be exposed, the differences between blood born infections and other potentially infectious materials, methods for dealing with potential exposures or spills, and the requirements from OSHA to protect workers from exposure or to track exposures if they occur.

What is the legal language of the FDA form 1572 or Device equivalent?

Form FDA 1572 is one of the primary documents needed when carrying out a clinical trial. Also called the Statement of Investigator; Form FDA 1572, called just 1572 informally, is a contract between the Principal Investigator (PI) and the FDA. This form contains all details of the subjects, as well as commitments from the PI.

It is a contract in which the Principal Investigator, the person who is in charge of the clinical trial, gives an undertaking to the FDA giving it the assurance that she will comply with all the requirements set out by the regulatory agency with regard to the trial.

By signing the FDA form 1572, which relates to IND studies, or the “Statement of the Investigator, which is meant for IDE studies; the PI is submitting herself to all the appropriate regulations, as this is a legally binding document by which they commit themselves to follow all of these.

The 1572 is meant to serve two important purposes:

It is a way of helping the FDA, as well as the sponsor of the study to qualify the PI, i.e., it gives the FDA and the sponsor of the study the opportunity to understand the Principal Investigator’s qualifications and ability to carry out the research in terms with the purposes it seeks to fulfil. It is also a way to verify that the site at which the clinical study is being carried out is appropriate for the study.

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The Form FDA 1572 also has another important purpose to fulfil.  It takes an undertaking from the Principal Investigator that the requirements set out by the FDA will be met during the trial. Failure to adhere to these commitments is considered a criminal offence, as something amounting to making false statements, and is liable for legal action under the terms set out in 18 USC 1001. This form has to be submitted whenever the sponsor selects the Principal Investigator to take charge of a clinical trial that is being conducted as an investigational new drug (IND) meets the criteria set out in 21 CFR 312.53 (c).

Other documents

Further, other documents such as 21 CFR 312.50, which deals with the General Responsibilities of Investigators, 21 CFR 812.100, which deals with the Responsibilities of Investigators for Biologics, and 21 CFR 812.110, which deals with the Responsibilities of Investigators for devices, need to be adhered to.

All these documents set out the general and specific responsibilities that the Investigators have when conducting a clinical trial. These start from who can qualify to be considered a PI to what qualification criteria sub investigators and research staff need to have.

A proper understanding of Form FDA 1572

FDA Form 1572 is thus an extremely important document that needs to be complied with fully if the clinical trial has to be considered compliant with the regulatory requirements. A full understanding of all the aspects that go into this will be spelt out at a webinar that Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, is organizing.

This webinar educates participants about the due diligence that investigators and their staff about their regulatory and legal responsibilities. Charles H. Pierce, a consultant in the Clinical Research/Drug-Device Development arena, will be the speaker at this webinar. In order to gain complete knowledge of this valuable guidance document, please enroll for this webinar by visiting signs the FDA form 1572

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There are nine statements in the FDA form 1572. Seven out of these begin with “I agree”. These are the important elements named in the 1572:

  • 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.

The GCP Guidelines of E6 (4) and the Compliance Program Guidance Manual (CPGM) 7348.811 outline additional responsibilities. It makes sense for PI and sponsors to comply with the principles of Good Clinical Practices (GCP), and to also use their common sense.

Charles will give a proper understanding of all these at this webinar. He will cover the following areas 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?