s**********8
发帖数: 25265 | 1 Good Laboratory Practice
In the experimental (non-clinical) research arena, the phrase good
laboratory practice or GLP specifically refers to a quality system of
management controls for research laboratories and organizations to try to
ensure the uniformity, consistency, reliability, reproducibility, quality,
and integrity of chemical (including pharmaceuticals) safety and efficacy
tests.
GLP was instituted following cases of animal test fraud by pharmaceutical
and industrial chemical (mainly pesticide) manufacturers. Industrial BioTest
Labs (IBT) was the most notable case, where thousands of safety tests for
chemical manufacturers were falsely claimed to have been performed or were
so poor that police investigators could not piece together what work had
been done...even though IBT superficially delivered the test results their
contracts with the manufacturers specified. [1]
The original GLP regulatory mandate was promulgated in 1978 by US-FDA (
though they may have got it from the New Zealand medicines agency) and
published in the Federal Register 43 FR 59985-60020. It was followed a few
years later by US-EPA, and (as outlined in the Organisation for Economic Co-
operation and Development (OECD) Principles of GLP in 1992) the OECD has
since help promulgate it to many countries, helping them place it into their
national regulations.
GLP applies to nonclinical studies conducted for the assessment of the
safety or efficacy of chemicals (including pharmaceuticals) to man, animals
and the environment. An internationally recognized definition of GLP can be
found on the website for the Medicines and Healthcare products Regulatory
Agency-UK which defines GLP as:
Good Laboratory Practice (GLP) embodies a set of principles that
provides a framework within which laboratory studies are planned, performed,
monitored, recorded, reported and archived. These studies are undertaken to
generate data by which the hazards and risks to users, consumers and third
parties, including the environment, can be assessed for pharmaceuticals (
only preclinical studies), agrochemicals, cosmetics, food additives, feed
additives and contaminants, novel foods, biocides, detergents etc.... GLP
helps assure regulatory authorities that the data submitted are a true
reflection of the results obtained during the study and can therefore be
relied upon when making risk/safety assessments.
GLP, a data quality system, should not be confused with standards for
laboratory safety - appropriate gloves, glasses & clothing to handle lab
materials safely.
Contents
[hide]
1 GLP and the OECD
2 GLP and the FDA
3 GLP and the European Union
4 GLP and non-OECD member-countries
5 Criticism of GLP
6 GLP and automated systems
7 Notes and references
8 See also
9 External links
[edit] GLP and the OECD
Following Decision C(97),186/Final of the OECD Council, data generated in
the testing of chemicals in one OECD Member Country, in accordance with OECD
Test Guidelines and the Principles of GLP are accepted in all other OECD
Member Countries. OECD Definition
GLP is a quality system concerned with the organisational processing process
and conditions under which non-clinical health and environmental safety
studies are planned, performed, monitored, recorded, archived and reported.[
2]
GLP principles include
Organization and Personnel
Management-Responsibilities
Sponsor-Responsibilities
Study Director-Responsibilities
Principle Investigator-Responsibilities
Study Personnel-Responsibilities
Quality assurance program
Quality Assurance Personnel
Facilities
Test System Facilities
Facilities for Test and Reference Items
Equipments, reagents and Materials
Test systems
Physical/Chemical
Biological
Test & Reference items
Standard operating procedures
Performance of Study
Study Plan
Conduct of Study
Reporting of results
Storage of Records and Reports
[edit] GLP and the FDA
The United States FDA has rules for GLP in 21CFR58. Preclinical trials on
animals in the United States of America use these rules prior to clinical
research in humans.
Research in the US not conducted under these restrictions or research done
outside US not conducted according to the OECD Guidelines (or FDA rules)
might be inadmissible in support of a New Drug Application in the US.
[edit] GLP and the European Union
Since 1987 the European Council had adopted two basic Directives and a
Decision relating to the application of the GLP principles. Directive 2004/
10/EC has replaced Directive 87/017/EEC as of 11 March 2004; Directive 2004/
9/EC has replaced Directive 88/320/EEC as of 11 March 2004.
" Directive 2004/10/EC of the European Parliament and of the Council of
11 February 2004 on the harmonisation of laws, regulations and
administrative provisions relating to the application of the principles of
good laboratory practice and the verification of their applications for
tests on chemical substances."
This directive lays down the obligation of the Member States to designate
the authorities responsible for GLP inspections in their territory. It also
comprises requirements for reporting and for the internal market (i.e.,
mutual acceptance of data).
" Directive 2004/9/EC of the European Parliament and of the Council of
11 February 2004 on the inspection and verification of good laboratory
practice (GLP)".
The Directive requires that the OECD Revised Guides for Compliance
Monitoring Procedures for GLP and the OECD Guidance for the Conduct of Test
Facility Inspections and Study Audits must be followed during laboratory
inspections and study audits.
89/569/EEC Council Decision of 28 July 1989 on the acceptance by the
European Economic Community of an OECD decision / recommendation on
compliance with principles of good laboratory practice.
There are also 'Product Oriented Directives' referring to GLP obligations:
Chemical substances; Regulation (EC) N° 1907/2006 (also known as the "
Evaluation, Authorisation and Restriction of Chemicals" Regulation, or "
REACH" regulation) of 18 December 2006 and Directive 2006/121/EC of 18
December 2006
Medicinal products; Directive 2001/83/EC on the Community code relating
to medicinal products for human use of 6 November 2001 as amended by
Commission Directive 2003/63/EC
Veterinary Medicinal Products; Directive 2001/82/EC of the European
Parliament and of the Council of 6 November 2001 on the Community code
relating to veterinary medicinal products
Cosmetics; Council Directive 93/35/EEC amending for the 6th time
directive 76/768/EEC
Feedingstuffs; Regulation (EC) No 1831/2003 of the European Parliament
and of the Council of 22 September 2003 on additives for use in animal
nutrition
Foodstuffs; Directive 89/107/EEC
Novel Foods and novel food ingredients; Regulation (EC) No 258/97 of the
European Parliament and of the Council of 27 January 1997 concerning novel
foods and novel food ingredients
Pesticides; Council Directive 91/414/EEC of 15 July 1991 concerning the
placing of plant protection products on the market
Biocides; Directive 98/8/EC of the European Parliament and of the
Council of 16 February 1998 concerning the placing of biocidal products on
the market
Detergents; Directive 98/8/EC Regulation (EC) No 648/2004 of the
European Parliament and of the Council of 31 March 2004 on detergents
EC Ecolabel; Commission Decision 2005/344/EC of 23 March 2005;
establishing ecological criteria for the award of the Community eco-label to
all-purpose cleaners and cleaners for sanitary facilities
In the meantime the EU has concluded Mutual Acceptance Agreements in the
area of GLP with Israel, Japan and Switzerland. By means of the Treaty of
the European Economic Area of 13 September 1993, the European Regulations
and Directives also apply to Iceland, Liechtenstein and Norway.
[edit] GLP and non-OECD member-countries
An inspection in non-member economies by OECD inspectors will not guarantee
that data generated in compliance with GLP will be accepted in other member
countries than the one to which they are submitting data and which has thus
sent inspectors to verify the accuracy of their compliance statement.
[edit] Criticism of GLP
GLP studies require adequate and permanent documentation of everything
involved in an experimental test: staff qualifications, valid study design,
standard operating procedures (SOPs), training, performance, formulation and
statistical analyses, and the retention of summary/individual data; so that
there can be confidence in the study's design, performance and its results,
and anyone (as public agencies have access to the GLP records) can
subsequently fully reconstruct the study.
In contrast, academic scientists also perform basic/exploratory experimental
research to: identify unknown potential hazards of chemicals, elucidate the
mode/mechanism of action for known toxicants, and explore novel toxic
endpoints. Accordingly, their experimental methods vary in the delivery
route of the test chemical, the number of test animals and the range of
doses. [3] Overall, their methods are far more varied than the GLP test
protocol is; and (at least before peer review) academics do not like to
share their results or methods with other laboratories competing for grant
money. These factors make it very hard for regulatory agencies to use the
results of academic researchers in chemical risk assessment.
Nonetheless, financially-independent academia's methods & data are heavily
critiqued by the best experts in their field (at scientific meetings), as
well as during peer-review of journal manuscripts. Thus financially-
independent academia's data tends to be the most reliable knowledge mankind
has.
As a controversy over ubiquitous plastics chemical bisPhenol-A (bPA)
continues (including several of the citations on this web page), it
perfectly illustrates the differences between GLP studies and independent
academia's safety studies. Regulatory agencies and industry cite the GLP-
compliant Tyl 2008 finding[4] of no bPA reproductive or developmental
toxicity in etrogen-sensitive mice, which also used a well validated dosing
route & amounts. But independent academics criticized its methods (e.g.
Myers et al. 2009 [5]), such as using an estrogenic feed for the test
animals (bPA binds to various estrogen receptors). Determinative results
rebutting specific claims of safety by the regulatory agencies and bPA
manufacturers--found that despite the assumption of rapid excretion if the
bPA is ingested (vs. directly injected), low doses of bPA by either exposure
route caused the same free bPA levels in serum, and the same amount pre-
cancerous cell growth in developing rodents' prostate (infants have not the
developed systems to excrete toxic chemicals; yet their developing organs,
such as the prostate here, are vulnerable to re-programing towards disease
by chemicals such as bPA).[6] In fact, not only is free (toxicologically
active) bPA transferred in utero to vulnerable developing animals, but
fetuses can actually de-conjugate (activate) bound bPA![7]
In contrast, the GLP regulatory safety studies sponsored by a chemical's
manufacturer, while uniform & more transparent, critically do not test much
at all; as follows:
The financial interest of the study sponsor in having their chemical
declared safe enough to use has been shown to bias the results of these
safety tests (for pharmaceuticals, many literature reviews have found this
correlation; for industrial chemicals, at least four literature reviews have
found the same thing, as summarized in a recent Commentary [8]);
Near poisoning-level doses, with linear extrapolation to the doses
humans are estimated to experience (this is due to expense--realistic lower
doses require much larger groups of test animals to reliably detect a
difference in outcome, versus the un-dosed control group), so our actual
exposures go untestsed--while hormone disrupting and perhaps other chemicals
are known to be more potent at low dose than at high dose!;
No tests of our actual mixed exposures;
Failure to test many endpoints, especially during the vulnerable ultra-
complexities of development;
CRITICALLY, any disease caused by the chemical is not allowed to develop
past the human-equivalent age of 60, when the dosing stops and the animals
are immediately killed for tissue analysis (in reality, most diseases occur
in older animals, including humans).
Critics of industry say that while GLP requirements have improved
reliability, regulatory safety and efficacy tests still rely entirely on the
data of the party with a massive financial interest that their chemical is
declared safe enough (or effective, if a pharmaceutical) to use.
Specifically, the GLP requirement entirely excludes the published scientific
literature from risk assessment, though they say that the latter is far
more reliable than industry's data. GLP acts as a shield to exclude relevant
data because: 1) regulatory agencies define GLP studies as being the
desired quality and so other data is not accepted, and 2) independent
academics do not need or like GLP, so they do not use it--they have their
own methods of data quality, as above.
The claimed result is that for many years, not one chemical risk assessment
performed to approve an agent for commercial use has used independent
toxicity data to determine the potency of its chemical--excluding hundreds
of thousands of published papers from the assessment. Instead, all such "
regulatory" risk assessments use only the toxicity data supplied by the
regulated party. Yet the independent literature invariably invalidates the
toxicity claims of industry's GLP studies--when the chemical has been on the
market long enough to be studied by academia--for example, Myers et al.
2009. [9]
In short, GLP is alleged to shield industry's safety claims from any
independent confirmation.
[edit] GLP and automated systems
Implementing GLP on an automated system, as an intellectual and labour-
intensive task, requires a GxP company to make a great amount of effort. To
ease the burden of this management, Webster et al. have provided a tutorial
for users to quickly embark on and do the job properly.[10]
[edit] Notes and references
^ Schneider, K (1983(Spring)). "Faking it: The case against Industrial
Bio-Test Laboratories". Amicus Journal (Natural Resources Defence Council):
14–26.
^ "OECD Principles of Good Laboratory Practice (as revised in 1997)".
OECD Environmental Health and Safety Publications (OECD) 1. 1998.
^ Tyl, Rochelle W. (2009). "Basic Exploratory Research Versus Guideline-
Compliant Studies Used for Hazard Evaluation and Risk Assessment: Bisphenol
A as a Case Study". Environmental Health Perspectives (NIEHS) 117 (11): 1644
–1651. doi:10.1289/ehp.0900893. PMC 2801172. PMID 20049112.
^ Tyl, RW; Myers CB, Marr MC, Sloan CS, Castillo NP, Veselica MM, Seely
JC, Dimond SS, Van Miller JP, Shiotsuka RN, Beyer D, Hentges SG, Waechter JM
Jr. (Aug 2008). "Two-generation reproductive toxicity study of dietary
bisphenol A in CD-1 (Swiss) mice". Toxicol Sci 104 (2): 362-84.
^ Myers, JP; vom Saal FS, Akingbemi BT, Arizono K, Belcher S, Colborn T,
Chahoud I, Crain DA, Farabollini F, Guillette LJ Jr, Hassold T, Ho SM, Hunt
PA, Iguchi T, Jobling S, Kanno J, Laufer H, Marcus M, McLachlan JA, Nadal A
, Oehlmann J, Olea N, Palanza P, Parmigiani S, Rubin BS, Schoenfelder G,
Sonnenschein C, Soto AM, Talsness CE, Taylor JA, Vandenberg LN, Vandenbergh
JG, Vogel S, Watson CS, Welshons WV, Zoeller RT (Mar 2009). "Why public
health agencies cannot depend on good laboratory practices as a criterion
for selecting data: the case of bisphenol A". Environ Health Perspect. 117 (
3): 309–15. doi:10.1289/ehp.0800173. PMC 2661896. PMID 19337501.
^ Prins, GS; Ye SH, Birch L, Ho SM, Kannan K (Jan 2011). "Serum
bisphenol A pharmacokinetics and prostate neoplastic responses following
oral and subcutaneous exposures in neonatal Sprague-Dawley rats". Reprod
Toxicol 31 (1): 1–9. doi:10.1016/j.reprotox.2010.09.009. PMC 3033961. PMID
20887781.
^ Nishikawa, Miyu; Hidetomo Iwano, Risa Yanagisawa, Nanako Koike, Hiroki
Inoue, Hiroshi Yokot (September 2010). "Placental Transfer of Conjugated
Bisphenol A and Subsequent Reactivation in the Rat Fetus". Environ Health
Perspect. 118 (9): 1196–1203. doi:10.1289/ehp.0901575. PMC 2944077. PMID
20382578.
^ Tweedale, AC (2011). "Uses of ‘Good Laboratory Practices’ by
regulated industry and agencies, and the safety of bisphenol A". J Epidemiol
Community Health (BMJ Group) 65 (6): 475e476. doi:10.1136/jech.2010.127761.
^ Myers JP et al. 2009.
^ Webster, Gregory K. et al.; Kott, L; Maloney, T (2005). "JALA Tutorial
Journal of the Association for Laboratory Automation (Elsevier) 10 (3): 182
–191. doi:10.1016/j.jala.2005.03.003.
[edit] See also
AutoAnalyzer
GxP
Good Automated Manufacturing Practice
Joint Committee for Traceability in Laboratory Medicine
International Laboratory Accreditation Cooperation
International Federation of Clinical Chemistry and Laboratory Medicine (
IFCC)
Drug development
ISO 15189
Verification and Validation
[edit] External links
Comparison of difference versions of GLP (Comparison OECD, FDA and EPA
GLP)
Medicines and Healthcare products Regulatory Agency-UK (MHRA-UK
definition of GLP)
current Good Analytical Laboratory Practice [cGALP]
Good Laboratory Practice (Organisation for Economic Co-operation and
Development)
OECD Series on Principles of Good Laboratory Practice and Compliance
Monitoring
Belgian Monitoring Authorithy for GLP
http://en.wikipedia.org/wiki/Good_Laboratory_Practice | s**********8
发帖数: 25265 | 2 non-clinical research GLP for both drugs and devices. | a*i
发帖数: 1652 | 3 这个GLP严格起来不胜其烦，到底FDA审查严到什么程度？
比如，用过的化学药品批号要记录。FDA真的会看你的笔记本吗？ | a*i
发帖数: 1652 | 4 到底什么是CRO? 这些机构会明白标识CRO吗？如果不是，那怎么判断？
for | s**********8
发帖数: 25265 | 5 GXP就是protocol说什么, 你就去做好拉, 就让让你去采便便, 做就好. 如果不去, 就
得写deviation rpt, 更能引起auditor注意.
notebook 要记录所有干过activity, 比如说化学药品, vendor, lot/batch number,
expiration date, 你用的哪pippetor prepared 溶液等等. notebook raw record is
the base of all quality manual.
【在 a*i 的大作中提到】
: 这个GLP严格起来不胜其烦，到底FDA审查严到什么程度？
: 比如，用过的化学药品批号要记录。FDA真的会看你的笔记本吗？
| a*i
发帖数: 1652 | 6 但有时候你得创建操作规程，然后发现还得改，改的时候还得看以前得数据是否受影响
。还得考虑某些报告得结论是否受影响。。。等等。。。不知道大家有什么体会。
is
【在 s**********8 的大作中提到】
: GXP就是protocol说什么, 你就去做好拉, 就让让你去采便便, 做就好. 如果不去, 就
: 得写deviation rpt, 更能引起auditor注意.
: notebook 要记录所有干过activity, 比如说化学药品, vendor, lot/batch number,
: expiration date, 你用的哪pippetor prepared 溶液等等. notebook raw record is
: the base of all quality manual.
| a*i
发帖数: 1652 | 7 这两者什么区别？请详细讲讲，想学习一下。谢谢！
GLP ? | a*i
发帖数: 1652 | 8 明白了，谢谢。看来要问问管理层了。但他们似乎说过"如果fda来查”这样得话。
realy
scope?
studies | s**********8
发帖数: 25265 | 9 GLP and GMP 当然可以开展R&D study.
GLP studies are mostly used for regulatory filing which should comply CFR58
, such as structure personnel, facility, QA, sampling, testing, data
management ect, everything needs a written protcol and all activties need
documentation for tracibility.
realy
scope?
studies | w*********l
发帖数: 5144 | 10 就是说GLP, GMP facility拉, 所有的人都trained, 并且有record; 所有的仪器都
qualified,并且有record, 有data management system in place, 有一整套的quality
manaual和sop构架等等.
做R&D的不一定有GXP的luxury, 但是GXP可以conduct R&D actitivies | a*i
发帖数: 1652 | 11 但有些情况下这样很无必要，比如大学研究所。
quality
【在 w*********l 的大作中提到】
: 就是说GLP, GMP facility拉, 所有的人都trained, 并且有record; 所有的仪器都
: qualified,并且有record, 有data management system in place, 有一整套的quality
: manaual和sop构架等等.
: 做R&D的不一定有GXP的luxury, 但是GXP可以conduct R&D actitivies
| w*********l
发帖数: 5144 | 12 当然. 除非做contract work
【在 a*i 的大作中提到】
: 但有些情况下这样很无必要，比如大学研究所。
:
: quality
| a*i
发帖数: 1652 | 13 对，管理层都是明白人。你怎么从业界进入政府部门的？给我指条路吧。 |
|
