FDA Guidance on Analytical Procedures and Methods Validation for Drugs and Biologics

The U.S. Food and Drug Administration released a final guidance on Analytical Procedures and Methods Validation for Drugs and Biologics.  The guidance document provides recommendations for submitting analytical procedures and methods validation data to support the documentation of the identify, strength, quality, purity and potency of drug substances and drug products.  The scope of the guidance document applies to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and supplements to these applications.

Read the Guidance document here

FDA Draft Guidance for Adaptive Designs for Medical Device Clinical Studies

The U.S. Food and Drug Administration (FDA) issued a draft guidance today for Adaptive Designs for Medical Device Clinical Studies.  The document provides guidance on how to plan and implement adaptive designs for clinical studies that allow for prospectively planned modifications based on accumulating study data without undermining the integrity and validity of a trial.

Read the full draft guidance here

The U.S. Food and Drug Administration's Center for Drug Evaluation and Research (CDER) will present a webinar on the draft guidance for industry, Use of an Electronic Informed Consent in Clinical Investigations: Questions and Answers, on Monday, 20 April 2015, from 1:00 p.m. – 2:00 p.m. EDT.

The guidance provides recommendations for clinical investigators, sponsors, and institutional review boards (IRBs) on the use of electronic media and processes to obtain informed consent for regulated clinical investigations.  A copy of the guidance may be found at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM436811.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery

Access the Webinar on Monday, 20 April 2015, from 1:00pm - 2:00pm using the following link: https://collaboration.fda.gov/guidancewebinars/

Draft FDA Guidance for Informed Consent

The U.S. Food and Drug Administration (FDA) published a new draft guidance for informed consent this July 2014.  The guidance is intended to provide information to clinical investigators, study sponsors and institutional review boards (IRBs) about the FDA's informed consent regulations.  When finalised, this guidance will supersede FDA's previous publication, "A Guide to Informed Consent" that was issued in September 1988.  

<< Click here to view the full guideline >>

The 7th System: Integrating Clinical Systems into a Comprehensive Quality Audit Program

Clinical quality systems are often managed independently of manufacturing and laboratory operations.  This can result in a fractured view of each compliance area (GCP, GMP and GLP) and a failure to provide adequate oversight of an organization’s overall compliance.  Using FDA’s six-system inspection model as a starting point, this article will discuss how to integrate the requirements of clinical quality systems with a GMP compliant quality program to provide a system for comprehensive quality oversight. (View the original article)

The goals of a quality audit program are: 

• to provide an accurate view of compliance across the organization, including suppliers and vendors; 
• to identify and prevent or correct compliance issues; and 
• to inform management of the compliance status of the organization.  

However, differences in the implementation of GMP (Good Manufacturing Practice) and GCP (Good Clinical Practice) compliance programs may occur due to the different focus of each program.  The GMP audit program is concerned with ensuring the identity, strength, safety, purity and effectiveness of the product or device, whereas the GCP audit program is focused on subject rights and safety, protocol conduct and data integrity.

Communication between the manufacturing and clinical disciplines may be obstructed in part by the use of different terminology, or by not using terms in the same manner to appropriately compare audit observations.  For example, use of the audit observation type “Validation” may describe an issue related to methods, equipment, packaging, or computer systems.  Without an appropriate description, this audit observation type is too ambiguous to be useful in assessing, preventing or correcting compliance issues.  “Investigational Product” is a common audit observation type used by clinical auditors, but this term is not sufficiently descriptive when relayed to manufacturing personnel as it does not describe whether the issue is related to the use, storage, labeling, or quality of an investigational product.

The use of different audit observation terminology and separate reporting systems may also obstruct an accurate assessment of the impact of systemic compliance issues and weaker compliance signals may be lost because they are maintained and reported separately. 

The accurate assessment of compliance with Standard Operating Procedures (SOPs), personnel training, vendor management, and complaints requires the ability to view issues across the organization, and the use of separate terms and reporting procedures may make it difficult to accurately quantify the total compliance risk of these activities or identify cross-functional issues that could impact investigational product integrity and/or subject safety.  Information from inspections of raw materials, production activities, packaging, labeling, warehouse and distribution, and clinical use may not be communicated effectively if issues are reported and communicated separately.

A shared quality system, using integrated audit observation categories, terminology and reporting can help to improve communication across functions and better meet the objectives of the quality audit program.  It should be noted that integrating the GMP and GCP quality audit programs does not necessitate a particular organization of the Quality Unit, although it is recommended to use the same system for assessing, reporting and resolving audit observations across the organization.

The Six-System Inspection Model defined by the U.S. Food and Drug Administration (FDA) provides an excellent foundation upon which to define the categories of a quality audit program. The model defines the following six systems:
• Quality System
• Facilities and Equipment System
• Materials System
• Production System
• Packaging and Labeling System
• Laboratory Control System

Most of the systems defined in the six-system model are readily transferable to audit observation categories useful for the inspection of both manufacturing and clinical activities.  Many clinical requirements can be integrated into the six-system model.  Within the Quality System, observation types such as audit program, complaints, deviations, personnel training and qualification, Standard Operating Procedures, and vendor qualification may be appropriate to both GMP and GCP activities.  Audit observation types related to the Facilities 
and Equipment System, such as calibration/preventive maintenance, equipment management, facility security, cleaning, and sanitation may be appropriate to both GMP and GCP functions.  However, audit observation types related to contamination controls, environmental monitoring, HVAC systems and water systems may be used primarily 

for manufacturing rather than clinical activities.  Although the six-system model provides an excellent starting point, not all clinical audit observations fit well into the six-system model.  

The addition of a seventh Clinical System can accommodate the addition of clinical audit observation types within an integrated inspection model.  Examples of audit observation types within the Clinical System may include: adverse events, case report forms/source documents, ethics committee, informed consent, monitoring, protocol compliance, regulatory approval, serious adverse events, trial management and oversight, and trial master file. Although it may be appropriate to create additional systems or categories (e.g., to distinguish safety from other trial management activities) for the purpose of this discussion we will 

create only one additional category for Clinical Systems (Figure 1).  With the integration of clinical requirements into FDA’s inspection model, and the addition of a Clinical System to accommodate additional GCP observation types, the seven-system inspection model provides an integrated structure of audit observation categories to help achieve the goals of the quality audit program.  The use of audit observation terms in the same manner to define, report and compare audit observations promotes improved transparency and communication between GMP and GCP functions, and a more accurate view of compliance across the  organization to effectively assess, communicate and resolve compliance issues identified by the quality audit program.

If you like this article, please recommend it using the social sharing links below:

FDA Issues Final Rule on Clinical Investigator Disqualification

The U.S. Food and Drug Administration (FDA) announced an amendment that will expand the scope of clinical investigator disqualification.  Under this new regulation, if the FDA Commissioner determines that a clinical investigator is ineligible to receive one kind of test article (drugs, devices or new animal drugs), the investigator will also be ineligible to conduct any clinical investigation that supports an application for a research or marketing permit for other kinds of products regulated by FDA.  This final rule is intended to help ensure adequate protection of research subjects and the quality and integrity of data submitted to FDA.  This rule will become effective May 30, 2012.

The final rule is available using the following web link: 

http://www.gpo.gov/fdsys/pkg/FR-2012-04-30/pdf/2012-10292.pdf

FDA Guidance: FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND

FDA issued the following guidance, "FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND, Frequently Asked Questions."  The guidance is intended to clarify the requirements if 21 CFR 312.120 and it also provides recommendations for IND's or MAA"s on how to provide evidence of GCP compliance of a non-IND foreign clinical study. 

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294729.pdf

FDA Guidance: IND Applications for PET Drugs

FDA's draft guidance summarizes the investigational new drug application (IND) process for unapproved positron emission tomography (PET) drugs, makes recommendations on how to submit an IND, provides advice on investigational PET drug access options, and describes the process for requesting permission to charge for an investigational PET drug.  Read the guidance at www.fda.gov:  Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs (PDF - 461KB)