Good Laboratory practice and current good manufacturing practice

Embed Size (px)

Text of Good Laboratory practice and current good manufacturing practice

  • A primerGood laboratory practice and current good manufacturing practice

    Foranalytical

    laboratories

  • A primerGood laboratory practice and current good manufacturing practice

    Ludwig Huber

    Agilent Technologies Deutschland GmbHHewlett-Packard-Strae 8 76337 WaldbronnGermanyludwig_huber@agilent.com

    Foranalytical

    laboratories

  • Copyright 2000-2002 Agilent Technologies Publication number 5988-6197ENPrinted in Germany 04/02

  • III

    FDA guidelines, industry validation groups

    and reference books help toimplement compliance in

    laboratories.

    Good Laboratory Practice (GLP) deals with the organization,process and conditions under which laboratory studies areplanned, performed, monitored, recorded and reported.GLP data are intended to promote the quality and validityof test data.

    (Current) Good Manufacturing Practice (cGMP) is thatpart of quality assurance which ensures that products areconsistently produced and controlled to the qualitystandards appropriate to their intended use.

    Published GLP and cGMP regulations have a significantimpact on the daily operation of an analytical laboratory.Weller1 gave an excellent practical explanation on what isexpected from working in a regulated environment:

    If experimental work is conducted in compliance withGLP, with or without the aid of computer, it should bepossible for an inspector, maybe four or five years hence,to look at the records of the work and determine easilywhy, how and by whom the work was done, who was incontrol, what equipment was used, the results obtained,any problems that were encountered and how they wereovercome.

    Unfortunately most laboratories have been in situations where they have had to interpret the regulationsthemselves. Procedures have been developed on an ad hoc basis, in isolation, in response to inspections by boththeir companys Quality Assurance Unit (QAU) andregulatory bodies.

    Preface

    Good Laboratory Practice and current Good Manufacturing Practice

  • IV

    Preface

    This situation has somewhat changed over the last coupleof years.

    1.Regulatory agencies such as the United Stated Food or Drug Administration (FDA) and internationalorganizations such as the International Conference on Harmonization (ICH) have developed guidancedocuments for implementation.

    2.Companies have formed validation groups anddeveloped procedures for qualification and validation ofequipment, computers and analytical methods

    3.Validation reference books have been published withclear guidelines, checklists and Standard OperatingProcedures (SOPs) on how to validate and qualifycomputerized systems and other equipment andmethods used in analytical laboratories2,3.

    In addition, some instrument vendors help users ofequipment and methods to comply with regulations. A good example is Agilent Technologies. Over the last ten years, at Agilent we have gained a goodunderstanding about the impact of regulations onanalytical laboratories. We also share this informationwith users of our equipment.

    In 1993 and 1994 we published the first and secondeditions of this primer. It has been translated into tenlanguages and more than 50,000 copies have beendistributed. Simultaneously we started to develop anddeliver SOPs and services for the Installation andOperational Qualification (IQ/OQ) of our analyticalproducts.

    The development and introduction of the 1100 SeriesHPLC was a breakthrough in validation & compliance. As a result of our experience and knowledge and of thetechnology available we were able to design automatedcalibration and validation features into the product.

    The 1100 Series HPLC hardware and software was

    designed for validation & compliance.

    The GLP/GMP primer has been translated into 10 languages and more

    than 100,000 copies have been distributed.

  • VThe product was introduced with software for automatedverification of the installation and for operationalqualification. A validation binder or CD-ROM has sincebeen made available to proof documented evidence ofvalidation during development. The QualificationWorkbook was later added to document all validationactivities.

    The results of several surveys made by LC/GC Magazineshow Agilent Technologies, formerly a part of Hewlett-Packard, as the number-one supplier for validation.

    Over the last few years we received many requests toupdate the GLP/GMP primer with news on regulations andguidelines. Our original plan was to remove GLP and GMPbasics. However, surveys amongst the target audienceshowed that there is still a need for such information,especially for new employees. Therefore the first twochapters are dedicated to the GLP/GMP background andbasics. Additional requests were made for more specificson equipment qualification, computer validation andelectronic records & signatures. Chapters three to eightdeal with this. Chapter nine discusses possible vendorcontributions and gives examples.

    Regulatory requirements, inspection and enforcementpractices are quite dynamic. What is appropriate todaymay not need to be appropriate tomorrow. Regulationschange but more often it is the inspection practices thatchange. In the early 90s the focus of inspections was onbasic requirements of GLP and GMP, but then it changedto equipment hardware and later on to software andcomputer systems. Today, the clear focus is on datasecurity, traceability and integrity of electronic records,driven mainly but not only by FDAs regulation 21 CFR Part 11.

    Good Laboratory Practice and current Good Manufacturing Practice

    Agilent is ranked as the preferred supplier

    for validation of hardware,software methods

    and data.

    The focus of FDA inspections has changed

    from equipment hardware tosoftware and now to data traceability, integrity and

    security.

  • VI

    Preface

    Paper documents are difficult to update. Therefore wehave decided to update this primer regularly on theInternet. In addition we would recommend the followingimportant sites where readers can get up-to-dateinformation.

    www.agilent.com/chem/validation

    www.fda.govUS FDA website. You can find regulations, guidancedocuments and warning letters.

    www.labcompliance.comWebsite dedicated to regulatory and compliance inlaboratories. It includes many links to other websites andhas an open discussion forum. It also includes referenceliterature and other documents for download.

    To comply with regulations can be quite expensive andsometimes it is just impossible to comply 100% even whenwilling, especially when new regulations are released. An example is 21 CFR Part 11 (electronic signatures &records) which was released in 1997 and nobody complied100% at that time.

    On-line resourcesthrough the internetkeep you up-to-date,

    day-by-day!

  • VII

    Good Laboratory Practice and current Good Manufacturing Practice

    The challenge is to find a good compromise between notdoing enough and doing too much. Lets take validation asan example. When complying right at the beginning of thevalidation process the additional value to each validationstep is tremendous. However, there is no added value intrying to validate each and every step and the incrementalcosts for validation goes up with each validation effort.The question is: where is the optimum or how muchvalidation is enough. The challenge is to find the optimumand this requires a thorough risk analysis. With the help ofthis primer and listed references it is hoped that thereader will get enough guideline to find this optimum forhis or her specific process.

    Ludwig HuberAgilent Technologies, April 2002

  • VIII

    Chapter 1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Historical perspective (GLP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

    Fraud and misinterpreted data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4FDAs reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5EPAs reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5GMP and cGMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

    National and international GLP regulations . . . . . . . . . . . . . . . . . . . . . . . 7Memoranda of Understanding (MOU) and bilateral agreements . . . . . . . . . . . . . . . . . . 7

    Who has to comply with GLP/cGMP regulations? . . . . . . . . . . . . . . . . 7Non-clinical laboratory studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Analysis under GMP and cGMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Availability of regulations and guidance documents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

    Chapter 2 GLP/GMP key provisions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11GLP organization and conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Study director . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Quality assurance unit (QAU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Standard operating procedures (SOPs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

    Title page . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .