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Method Validation / Reference Standards

Download more than 350 documents: SOPs, examples, templates, checklists, FDA waning letters, 483 inspectional observations, FDA and other official guidelines, presentations/publications from FDA personnel.

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Standard Operating Procedures

SOP
Handling Out-of-Specification Results

S-115

The FDA requires that an investigation be conducted whenever an Out-of-Specification (OOS) result is observed. This SOP defines the requirements for dealing with OOS results. Even if a batch is rejected based on an OOS result, the investigation is necessary to determine if the result is associated with other batches of the same drug product or other products. This SOP deals with results that fall outside the specifications or acceptance criteria established in new drug applications, official compendia, or by the manufacturer and suspect within test results. The SOP applies to OOS as a result of analytical errors, process errors and manufacturing errors.

 

SOP
Handling Out-of-Trend Situations

S-116

 

SOP
Using Electronic Laboratory Notebooks in FDA Regulated Environments

S-268

Electronic Laboratory Notebooks (ELN) are frequently used in regulated development and QC laboratories. The purpose of this operating procedure is to ensure that ELNs used in regulated environments comply with regulations . Following this SOP does not mean that users comply with all regulations in all aspects. The procedure applies whenever Electronic Laboratory Notebooks are used in a regulated environments  

 

SOP
Change Control of Analytical Equipment

S-509

 

SOP
Auditing Analytical Laboratories

S-511

 

SOP
Validation of Chromatographic Methods

S-613

Follow this step-by-step SOP to develop and document your chromatographic method. It includes validation parameters and examples for acceptance limits.

 

SOP
Transfer of Analytical Methods

S-614

Accurate and consistent analytical data can only be obtained with validated methods. When validated methods are transferred between laboratories and sites, their validated state should be maintained to ensure the same reliable results in the receiving laboratory. This SOP addresses the process for transferring validated analytical methods.

 

SOP
Verification of Compendial Methods

S-615

 

SOP
Change versus Adjustment of Compendial Methods

S-617

 

SOP
Risk Based Validation of Laboratory Computer Systems

S-662

Templates / gap analyses / checklists / case studies / examples

Checklist
Out of Specification Situations (OOS)

E-116

 

Checklist
Laboratory Computer Systems

E-158

Laboratory computer systems used in regulated environments should be validated and well controlled. This form helps to identify qualification and validation requirements for software and computer systems

 

Checklist
Using Electronic Laboratory Notebooks in FDA Regulated Environments

E-164

 

Checklist
Validation of Analytical Methods

E-171

 

Checklist
 System Suitability Testing

E-176

 

Checklist
Laboratory audit

E-184

Use this checklist to audit your laboratory. It is also most useful to learn what 3rd party auditors and regulatory inspectors will look at.

 

Checklist
 Requirement Specifications - Chromatography Data System

E-781-02

 

Reference papers and presentations, private authors

 

Journal publication
Reference Paper: (Laboratory) Equipment Qualification and Computer System Validation

A-552

 

Reference Paper
Validation of Analytical Methods: Review and Strategy

A-603

Published in LC/GC Magazine. Reference paper with advice when, what and how to validate and revalidate analytical methods. Takes into account USP and ICH guidelines.

 

Reference Paper
Validation of HPLC Methods

A-605

Published in BioPharm. This paper gives a strategy for the validation of HPLC methods developed in house and a recommendation on the implementation. It also recommends a list of documents that should be produced during, and on completion of, validation.

 

Reference Paper
Validation of Standard Methods

A-607

Published in PharmTech. The paper answers a frequent question: do I need to validate Standard methods, such as USP, ASTM or ISO., and if so what should be validated and how

 

Reference Paper
Preparation and Qualification of Certified Reference Material and Working Standards.

A-633

Published in BioPharm. This paper gives recommendations for the preparation of reference materials and how to implement a quality assurance program for purchased and home made reference standards.

 

Reference Paper
Traceability of Analytical Measurements

A-635

This article from Carl Craig, Ph.D., General Manager,
Pharmaceutical Resource Associate explains the concept of traceability and gives practical examples on how in implement traceability in chemical measurement

 

Presentation
L. Huber: Validation of Analytical Methods and Procedures

P-561

Design, Conduct and Document for Efficiency and Compliance.

FDA regulations and official FDA Guidelines

 

FDA Guidance
Analytical Procedures and Methods Validation

F-505 

Draft

 

FDA Guidance
Bioanalytical Method Validation

F-507

Other regulations, official guidelines and recommendations from industry task forces

 

Presentations, publications, interviews with FDA personnel (these are not official guidelines)

 

FDA Presentation
FDA Perspective on Laboratory Inspections

G-262

Yvonne McKnight, chemist at the FDA Philadelphia gave a presentation at the IVT conference "Laboratory Controls & Compliance" in Philadelphia on April 11, 2005. More than 120 delegates listened to the presentation entitled: Inspection Issues in the Analytical Laboratory: An FDA Perspective". During the presentation McKnight quoted and discussed FDA regulations and enforcement activities, she gave advice on how to prepare for FDA inspections and reported on recent trends and statistics of inspectional deviations. Highlight of the presentation was a TOP TEN list with 483 inspectional observations.

 

FDA Presentation
Insight on FDA Inspections and Recommendations

G-263

Sybil Wellstood, Ph.D., of FDA CDRH Division of Bioresearch monitoring gave a presentation on FDA's Bioresearch and In Vitro Diagnostics. The objective was to provide an overview of the CDRH Bioresearch monitoring program (BIMO) and to discuss how the BIMO program applies to in vitro diagnostic (IVD) studies conducted under 510(k) pre-market notifications. One of the responsibilities of the Office of Compliance is to develop and issue inspection assignments to field offices, to evaluate and classify Establishment Inspection reports and to initiate follow-up regulatory actions and correspondence. In line with this responsibility Dr. Wellstood gave an insight on FDA inspections: the inspection process, whom they inspect, their expectations, type of inspections and how an inspections is conducted, concluded and followed up. An FDA 483 form report is written right after the inspection with deviations from regulations. Deviations from guidelines do not appear on the Form FDA-483, but may be included in the discussion" she said. She also recommended to respond verbally during the final discussion and/or sent a written response to District Office.

 

FDA Presentation
T. Savage, US FDA: Laboratory GMPs and Inspectional Issues:
an FDA Perspective

G-268

A Regulatory Perspective by Patrick J. Faustino, Ph.D, Office of Pharmaceutical Science, Analytical Methods Technical Committee, Center for Drug Evaluation and Research, U.S. Food and Drug Administration.
Shows the direction of the FDA towards method validation practices.

 

FDA Presentation
Edwin Rivera: Investigating OOS Test Results for Pharmaceutical

G-334

 

FDA Presentation:
How much can you change an official method before it isn't the official method any more?

G-425

Presented by William B. Furman from the US FDA. This question comes frequently when methods are transferred from development to manufacturing or when the equipment manufacturer is changed. Examples are HPLC flow rate, pH of mobile phase, column temperature and others. 

 

FDA Presentation
Analytical Methods Validation

G-427

A Regulatory Perspective by Patrick J. Faustino, Ph.D, Office of Pharmaceutical Science, Analytical Methods Technical Committee, Center for Drug Evaluation and Research, U.S. Food and Drug Administration.
Shows the direction of the FDA towards method validation practices.